Trial Outcomes & Findings for A Study of an Encapsulated Cell Technology (ECT) Implant for Patients With Atrophic Macular Degeneration (NCT NCT00447954)

Last Updated: 2025-03-28

Results Overview

Response is defined as a improvement from baseline at Month 12 in monocular best visual acuity (BCVA) in the study eye of at least 10 letters as assessed by standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

53 participants

Primary outcome timeframe

1 year post-implant

Results posted on

2025-03-28

Participant Flow

The study had a double-masked, multi-center, randomized, parallel group design. Patients were randomized on a 2:1:1 basis to the higher CNTF output NTC-201-6A.02 implant, the lower CNTF output NTC-201-10.02 implant or to sham surgery. A total of 53 patients were randomized to the treatment groups: 27 patients to the higher CNTF output NTC-201-6A.02 implant, 13 patients to the lower CNTF output NTC-201-10.02 implant and 13 patients to sham surgery.

Two patients withdrew following randomization but prior to the implantation/sham surgery procedure (one in the low-output implant arm and one in the sham surgery arm). Four patients withdrew early, all in the high dose treatment group. In two cases, withdrawal was due to AEs; one patient was lost to follow up and one withdrew consent.

Unit of analysis: Eyes

Participant milestones

Participant milestones
Measure	Low Dose NT-501 implant: Low Dose encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina	High Dose NT-501 implant: High Dose encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina	Sham No implant (Sham procedure) Non-penetrating sham procedure to mimic implant procedure
Overall Study STARTED	13 13	27 27	13 13
Overall Study COMPLETED	12 12	23 23	12 12
Overall Study NOT COMPLETED	1 1	4 4	1 1

Reasons for withdrawal

Reasons for withdrawal
Measure	Low Dose NT-501 implant: Low Dose encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina	High Dose NT-501 implant: High Dose encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina	Sham No implant (Sham procedure) Non-penetrating sham procedure to mimic implant procedure
Overall Study Adverse Event	0	2	0
Overall Study Withdrawal by Subject	0	1	1
Overall Study Lost to Follow-up	0	1	0
Overall Study Exclusionary event prior to implant procedure	1	0	0

Baseline Characteristics

N=number of eyes assessed in all treated participants (mITT population)

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 1 year post-implant

Population: N=number of eyes assessed in all treated participants (mITT population)

Outcome measures

Outcome measures
Measure	Low Dose n=12 eyes NT-501 implant: Low Dose	High Dose n=27 eyes NT-501 implant: High Dose	Sham n=12 eyes No implant (Sham Procedure)
BCVA Response Defined as an Increased in 10 Letters at 1 Year Post-implant Response	3 eyes	3 eyes	1 eyes
BCVA Response Defined as an Increased in 10 Letters at 1 Year Post-implant No Response	9 eyes	24 eyes	11 eyes

SECONDARY outcome

Timeframe: From initial implant 18 months post-implant

Population: N=number of eyes assessed in all treated participants (mITT population)

Change from baseline at post-baseline visits in monocular best visual acuity (BCVA) as assessed by standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart.

Outcome measures

Outcome measures
Measure	Low Dose n=12 eyes NT-501 implant: Low Dose	High Dose n=27 eyes NT-501 implant: High Dose	Sham n=12 eyes No implant (Sham Procedure)
The Change in BCVA Over the 18-month Follow-up Period 1 month post-implant - Treated	-0.1 Letter score (number of letters) Standard Deviation 6.6	1.5 Letter score (number of letters) Standard Deviation 5.5	1.4 Letter score (number of letters) Standard Deviation 6.2
The Change in BCVA Over the 18-month Follow-up Period 1 month post-implant - Untreated	1.0 Letter score (number of letters) Standard Deviation 6.1	2.9 Letter score (number of letters) Standard Deviation 6.5	0.5 Letter score (number of letters) Standard Deviation 3.1
The Change in BCVA Over the 18-month Follow-up Period 3 months post-implant - Treated	-4.4 Letter score (number of letters) Standard Deviation 7.9	3.0 Letter score (number of letters) Standard Deviation 4.7	2.1 Letter score (number of letters) Standard Deviation 8.8
The Change in BCVA Over the 18-month Follow-up Period 3 months post-implant - Untreated	-0.5 Letter score (number of letters) Standard Deviation 4.4	2.3 Letter score (number of letters) Standard Deviation 6.1	-0.5 Letter score (number of letters) Standard Deviation 6.7
The Change in BCVA Over the 18-month Follow-up Period 4 months post-implant - Treated	-0.8 Letter score (number of letters) Standard Deviation 11.2	3.0 Letter score (number of letters) Standard Deviation 5.9	2.9 Letter score (number of letters) Standard Deviation 7.7
The Change in BCVA Over the 18-month Follow-up Period 4 months post-implant - Untreated	-1.0 Letter score (number of letters) Standard Deviation 5.4	2.9 Letter score (number of letters) Standard Deviation 7.2	0.3 Letter score (number of letters) Standard Deviation 7.3
The Change in BCVA Over the 18-month Follow-up Period 6 months post-implant - Treated	-0.1 Letter score (number of letters) Standard Deviation 11.8	2.7 Letter score (number of letters) Standard Deviation 5.3	-0.4 Letter score (number of letters) Standard Deviation 7.7
The Change in BCVA Over the 18-month Follow-up Period 6 months post-implant - Untreated	-1.6 Letter score (number of letters) Standard Deviation 9.3	1.5 Letter score (number of letters) Standard Deviation 7.7	-1.9 Letter score (number of letters) Standard Deviation 6.1
The Change in BCVA Over the 18-month Follow-up Period 12 months post-implant - Treated	-0.3 Letter score (number of letters) Standard Deviation 15.9	-0.2 Letter score (number of letters) Standard Deviation 8.4	-1.3 Letter score (number of letters) Standard Deviation 11.1
The Change in BCVA Over the 18-month Follow-up Period 12 months post-implant - Untreated	-4.6 Letter score (number of letters) Standard Deviation 17.9	-1.8 Letter score (number of letters) Standard Deviation 14.4	-6.0 Letter score (number of letters) Standard Deviation 9.6
The Change in BCVA Over the 18-month Follow-up Period 18 months post-implant - Treated	-1.8 Letter score (number of letters) Standard Deviation 18.4	-5.3 Letter score (number of letters) Standard Deviation 15.0	-4.1 Letter score (number of letters) Standard Deviation 13.7
The Change in BCVA Over the 18-month Follow-up Period 18 months post-implant - Untreated	-7.0 Letter score (number of letters) Standard Deviation 14.6	-3.7 Letter score (number of letters) Standard Deviation 13.5	-8.5 Letter score (number of letters) Standard Deviation 11.1

Adverse Events

Low Dose

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

High Dose

Serious events: 10 serious events

Other events: 8 other events

Deaths: 1 deaths

Sham

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

CMO

Neurotech Pharmaceuticals, LLC

Phone: 401-333-3880

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Low Dose n=13 eyes NT-501 implant: Low Dose	High Dose n=27 eyes NT-501 implant: High Dose	Sham n=13 eyes No implant (Sham Procedure)	Total n=53 eyes Total of all reporting groups
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=13 Participants	0 Participants n=27 Participants	0 Participants n=13 Participants	0 Participants n=53 Participants
Age, Continuous	78.3 Years STANDARD_DEVIATION 5.6 • n=13 Participants	74.9 Years STANDARD_DEVIATION 7.5 • n=27 Participants	74.5 Years STANDARD_DEVIATION 6.0 • n=13 Participants	75.6 Years STANDARD_DEVIATION 6.8 • n=53 Participants
Sex: Female, Male Female	6 Participants n=13 Participants	17 Participants n=27 Participants	5 Participants n=13 Participants	28 Participants n=53 Participants
Sex: Female, Male Male	7 Participants n=13 Participants	10 Participants n=27 Participants	8 Participants n=13 Participants	25 Participants n=53 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=13 Participants	0 Participants n=27 Participants	0 Participants n=13 Participants	0 Participants n=53 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=13 Participants	27 Participants n=27 Participants	13 Participants n=13 Participants	53 Participants n=53 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=13 Participants	0 Participants n=27 Participants	0 Participants n=13 Participants	0 Participants n=53 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=13 Participants	0 Participants n=27 Participants	0 Participants n=13 Participants	0 Participants n=53 Participants
Race (NIH/OMB) Asian	0 Participants n=13 Participants	0 Participants n=27 Participants	0 Participants n=13 Participants	0 Participants n=53 Participants
Race (NIH/OMB) Black or African American	0 Participants n=13 Participants	0 Participants n=27 Participants	0 Participants n=13 Participants	0 Participants n=53 Participants
Race (NIH/OMB) White	13 Participants n=13 Participants	27 Participants n=27 Participants	13 Participants n=13 Participants	53 Participants n=53 Participants
Race (NIH/OMB) More than one race	0 Participants n=13 Participants	0 Participants n=27 Participants	0 Participants n=13 Participants	0 Participants n=53 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=13 Participants	0 Participants n=27 Participants	0 Participants n=13 Participants	0 Participants n=53 Participants
Ocular History Years since first diagnosed with AMD	6.75 Years STANDARD_DEVIATION 6.81 • n=13 Participants	8.39 Years STANDARD_DEVIATION 6.82 • n=27 Participants	9.84 Years STANDARD_DEVIATION 9.06 • n=13 Participants	8.34 Years STANDARD_DEVIATION 7.36 • n=53 Participants
Ocular History Years since ocular disease	2.89 Years STANDARD_DEVIATION 3.54 • n=13 Participants	3.44 Years STANDARD_DEVIATION 4.34 • n=27 Participants	5.93 Years STANDARD_DEVIATION 9.63 • n=13 Participants	3.92 Years STANDARD_DEVIATION 5.92 • n=53 Participants
Ocular History Years since ocular surgery	5.99 Years STANDARD_DEVIATION 6.13 • n=13 Participants	4.73 Years STANDARD_DEVIATION 4.31 • n=27 Participants	2.49 Years STANDARD_DEVIATION 1.66 • n=13 Participants	4.65 Years STANDARD_DEVIATION 4.64 • n=53 Participants
Ocular History Years since ocular treatment	1.60 Years STANDARD_DEVIATION 0.0 • n=13 Participants	5.18 Years STANDARD_DEVIATION 3.68 • n=27 Participants	2.63 Years STANDARD_DEVIATION 0.0 • n=13 Participants	3.65 Years STANDARD_DEVIATION 2.79 • n=53 Participants
Type of Ocular History Ocular Disease	13 Participants n=13 Participants	27 Participants n=27 Participants	13 Participants n=13 Participants	53 Participants n=53 Participants
Type of Ocular History Ocular Surgery	9 Participants n=13 Participants	13 Participants n=27 Participants	6 Participants n=13 Participants	28 Participants n=53 Participants
Type of Ocular History Ocular Treatment	1 Participants n=13 Participants	2 Participants n=27 Participants	1 Participants n=13 Participants	4 Participants n=53 Participants
Baseline BCVA Treated Eye	49.9 Letter score (# of letters read correct) STANDARD_DEVIATION 10.2 • n=13 eyes • N=number of eyes assessed in all treated participants (mITT population)	53.5 Letter score (# of letters read correct) STANDARD_DEVIATION 9.0 • n=27 eyes • N=number of eyes assessed in all treated participants (mITT population)	56.3 Letter score (# of letters read correct) STANDARD_DEVIATION 6.6 • n=13 eyes • N=number of eyes assessed in all treated participants (mITT population)	53.2 Letter score (# of letters read correct) STANDARD_DEVIATION 8.6 • n=53 eyes • N=number of eyes assessed in all treated participants (mITT population)
Baseline BCVA Untreated Eye	55.7 Letter score (# of letters read correct) STANDARD_DEVIATION 23.2 • n=13 eyes • N=number of eyes assessed in all treated participants (mITT population)	55.0 Letter score (# of letters read correct) STANDARD_DEVIATION 21.6 • n=27 eyes • N=number of eyes assessed in all treated participants (mITT population)	68.1 Letter score (# of letters read correct) STANDARD_DEVIATION 9.1 • n=13 eyes • N=number of eyes assessed in all treated participants (mITT population)	59.6 Letter score (# of letters read correct) STANDARD_DEVIATION 18.0 • n=53 eyes • N=number of eyes assessed in all treated participants (mITT population)

Serious adverse events
Measure	Low Dose n=12 participants at risk NT-501 implant: Low Dose encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina	High Dose n=27 participants at risk NT-501 implant: High Dose encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina	Sham n=12 participants at risk No implant (Sham procedure) Non-penetrating sham procedure to mimic implant procedure
Cardiac disorders Acute Myocardial Infarction	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Cardiac disorders Atrial Fibrillation	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/27 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Cardiac disorders Cardiac Arrest	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Choriodal Neovascularisation	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/27 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Retinal Haemorrhage	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/27 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Gastrointestinal disorders Diverticulum	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
General disorders Fatigue	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/27 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Infections and infestations Cellulitis	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Infections and infestations Diverticulitis	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Infections and infestations Pneumonia	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Injury, poisoning and procedural complications Gastroenteritis Radiation	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Injury, poisoning and procedural complications Hip Fracture	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Neoplasm Malignant	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic Neoplasm	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Leiomyoma	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Nervous system disorders Carotid Artery Occlusion	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Psychiatric disorders Mental Status Change	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Reproductive system and breast disorders Postmenopausal Haemorrhage	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/27 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Vascular disorders Haematoma	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Vascular disorders Peripheral Arterial Occlusive Disease	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Vascular disorders Peripheral Ischaemia	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.

Other adverse events
Measure	Low Dose n=12 participants at risk NT-501 implant: Low Dose encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina	High Dose n=27 participants at risk NT-501 implant: High Dose encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina	Sham n=12 participants at risk No implant (Sham procedure) Non-penetrating sham procedure to mimic implant procedure
Eye disorders Anterior Chamber Cell	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	7.4% 2/27 • Number of events 2 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Anterior Chamber Flare	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/27 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Cataract	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Cataract Cortical	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Cataract Subcapsular	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Conjuctival Haemorrhage	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	11.1% 3/27 • Number of events 3 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Conjunctival Hyperaemia	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	7.4% 2/27 • Number of events 2 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Eye Discharge	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Eye Irritation	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	7.4% 2/27 • Number of events 2 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Eye Pain	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	7.4% 2/27 • Number of events 2 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Eye Pruritis	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Eyelid Ptosis	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Lacrimation Increased	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Miosis	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Ocular Hyperaemia	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/27 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Photopsia	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Retinal Haemorrhage	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Visual Disturbance	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Vitreous Disorder	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Eye disorders Vitreous Haemorrhage	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Infections and infestations Eye Infection	8.3% 1/12 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/27 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Injury, poisoning and procedural complications Suture Related Complication	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	14.8% 4/27 • Number of events 4 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Investigations Intraocular Pressure Increased	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.
Metabolism and nutrition disorders Diabetes Mellitus	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	3.7% 1/27 • Number of events 1 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.	0.00% 0/12 • All patients were to be followed clinically for 18 months. Patients could have the implant removed (explanted) from the eye after 12 months or earlier in case of adverse events (AEs) or at the patient's request. Patients were followed up to 18-months post implant. No serious adverse events or study withdrawals related to the implantation procedure or the active study treatment. Although all patients experienced at least one AE during the study period, the majority were mild or moderate in severity. No severe or life-threatening AEs were considered to be related to the study treatments or study procedures. One SAE (cardiac arrest experienced by a patient in the high dose group) resulted in death. There were no other deaths during the study.