P050034The Implantable

Miniature Telescope (IMT™)

Presented by Bernard P. Lepri, OD, MS, MEd

FDA/CDRH/ODE/DOEDJuly 14, 2006

Special Thanks!

Gene Hilmantel, OD, MS – the Rosetta Stone of biostatistics

Bruce Drum, PhD – the walking guide to visual science and contributor of the visual science slides of this presentation today.

The proposed indication reads:

The IMT™ is indicated for use in adult patients with bilateral, stable, untreatable, moderate to profound central vision impairment due to macular degeneration as determined by fluorescein angiography, and cataract in patients who

Indications (continued)

are 55 years of age or older;

Have BCDVA of 20/80 to 20/800;

Have Adequate peripheral vision in the nonoperative eye; and

Demonstrate a minimum 5 letter improvement on ETDRS chart with an external telescope

Study Design

• prospective, multicenter clinical trial

• 28 clinical sites

•conducted in the U.S. under IDE

•218 consecutive patients were enrolled

•206 patients were implanted and evaluated

•Mean age was 75.4 years ± 7.2

•followed over a 24-month period 1 day, 1 wk, 1-, 3-, 6-, 9-, 12-, 18- and 24-month postoperatively.

Effectiveness Endpoints

≥2 lines BCDVA/BCNVA in 50% of eyes @ 12 mos. Postop – primary endpoint.

Quality of Life surveys (ADL and VFQ-25) - secondary measurements of procedure success.

Safety EndpointsEndothelial cell loss: Mean % ECD loss ≤17% at 1yr. postop – primary– average ECD loss; large-incision cataract surgery;

reported in literature

≤10% eyes lose ≥2 lines BCDVA or BCNVA without a gain of ≥2 lines in BCVA – secondary

Adverse events and complications – no preset targets.

Clinical Safety

•Preop ECD ≥ 1600 Cells/mm2

•Minimum ACD ≥2.5mm

•Minimum Age ≥55

Mean Decrease in ECD (overall cohort)

• 25.3% at 1 year • 28.2% at 2 years. • 12.5% (CI: 7.6% to 19.0%) of eyes available at 2 years

had ECD counts of <1000 cells/mm2 • 90th percentile @ 2 years (10% with greatest loss)

was:

·         60% ECD loss - IMT-implanted eyes

·         12% ECD loss - fellow eyes.  

Endothelial Cell Density Loss

0%10%20%30%40%50%60%70%80%90%

100%

EC

D lo

ss >

20%

3 mth 12 mth 18 mth 24 mth

IMT eyesFellow eyes

ECD Considerations

No morphometric data on ECD was presented by the sponsor.High ACD loss – due surgical order; first three casesEyes with ACDs of < 3mm had the greatest losses at all time periods and especially at 24 months, where approximately 1/3 of ECD has been lost. Surgical specialty – corneal surgeons had the lowest surgical loss rates

ECD Considerations (continued)

60 years old - 22 more years (82 years old)90 years old - 5 more years (95 years old) Minimum acceptable level of ECD for future cataract surgery is 1500 cells/mm²800 cells/mm² - potential corneal edema

Percentage of Eyes with Predicted ECD ≤1000

0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

2 years 3 years 4 years

IMT

Fellow

ECD Loss Stratified by ACD

Postop Interval

Anterior Chamber Depth

3.00mmMean loss

>3.00-3.50mm(∆ Mean loss as

compared to ACD 3.00mm)

>3.50mm(∆ Mean loss

as compared to ACD

3.00mm)

3 months 22.1% 19.3%(2.8% less)

16.2% (5.9% less)

6 months 26.3% 20% (6.3% less)

18.8% (7.5% less)

12 months 27.0% -25.0% (2.0% less)

22.3% (4.7% less)

24 months 31.7% 26.9%(4.8% less)

24%(7.7% less)

ACD & Corneal Clearance

IMT is designed for a 2mm corneal endothelial clearanceMinimum ACD was ≥2.5mmNo substudies or data presented to establish suitability of minimum ACD for the established minimum clearance

Haptic Placement

N %

Superior Loop Bag 198 96.1

Sulcus 8 3.9

Inferior Loop Bag 201 97.6

Sulcus 5 2.4

Posterior Capsular Opacification

1/174 (0.6%) @18 months

2/147 (1.4%) @ 24 months.

Zero (0) YAG Capsulotomies

Needling - two patients with visually

significant PCO.

PCO Management

YAG capsulotomy can damage the IMT lenses.

Capsulotomy through the

periphery of the telescope » No patient data available

» Rabbit studies performed

Potential Problems with YAG Procedures

Can only be done around the periphery of the IMTIncreases the # of bursts and total amount of energy delivered to the eyeIncreases risk of Retinal DetachmentPosterior movement of the IMT

Clinical Effectiveness

Visual Acuity

Quality of Life

Categories of Vision Loss

Visual impairment – – BCDVA ≤ 20/40 but better than 20/200.

Legal blindness – BCDVA ≤ 20/200 – visual field diameter < 10 degrees.

Low vision < 20/60 in the better eye.

Preop VA Values - IMT

The preoperative Acuity range was 20/80 - 20/800mean preop BCDVA - 20/312mean preop BCNVA

–@ 8 inches - 20/315 –@ 16 inches was 20/262

Implantation profile

115 eyes were implanted with the

2.2X

91 eyes were implanted with the

3.0X

Improvement in Vision

Improvement of ≥ 2 lines BCDVA or BSNVA = 85% to 90%Improvement of ≥ 2 lines BCDVA and BSNVA = 67% to 73%52.8% (102/193) gained ≥ 3 lines BCDVA and BCNVA

VA Improvements ≥2 lines

90.1% of implanted eyes were reported to have had an improvement of ≥2 lines in either BCDVA or BCNVA at 12-months postop.

Refractive devices – baseline ≥20/40

Reliability of Low Vision Measures - Russell Woods and Jan Lovie-Kitchin

HCVA logMAR

LCVA logMAR

PRC log contrast units

METlog contrast units

Young Normal .07 0.15

Normal Uncorrected

0.17 0.15

Normal Optically degraded

0.17-0.27 0.18-0.34 0.22-0.36

Moderate Ocular Disease

0.09-0.19 0.19 0.39

LV in Laboratory

0.17

LV in Clinic 0.29 0.25 0.38 0.38

BCDVAChange from

Baseline

Moderate Impairment

(20/80 to 20/160)

Severe Impairment(20/161 to

20/400)

Profound Impairment(Worse than

20/400)

n % n % n %

Gain 3 lines 4 23.5% 46 55.4%

36 76.6

%

Gain 2 lines but <3 lines

4 23.5% 13 15.7% 5 10.6%

Gain 1 line but <2 lines

2 11.8% 10 12.0% 4 8.5%

Other 7 41.2% 14 16.9% 2 4.3%

Gain 2 lines 8 47.1% 59 71.1% 41 87.2%

N 17 83 47

Not reported/IMT removal

0 1 0

Total 17 84 47

Predicted EffectivenessDistance Visual Acuity

IMT Model Mean Preop

BCDVA

Predicted Postop BCDVA

24 Months Postop

3X (2.7X)

20/312 ~20/115(~3 line

improvement)

Mean

BCDVA

20/1502.2X 20/312 ~20/142

(~3 line improvement

)

Predicted EffectivenessNear Visual Acuity

Near Distance

Mean Preop BCNVA

Predicted Postop BCDVA

Mean BCNVA @

24 Months Postop

8 inches 20/315 ~20/105(~3 line

improvement)20/190.2

16 inches 20/262 ~20/87(~3 line

improvement)20/157.6

Adjusted vs. Actual Acuities?

IMT measured acuity will theoretically

increase by ~3.4 or ~4.3 lines,

respectively for the 2.2 & 3.0X

2 line loss = 5.4 or 6.3 lines

improvement of <1.4 or 2.3 = a loss of

>2 lines

Safety & Effectiveness

Vision Rehabilitation

• Functional Vision

• Orientation & Mobility

• Reading

VFQ-25 - Items 5, 6, 7, 8, and 9

Independent mobility,

Reading street signs and names of

stores,

Negotiating steps and curbs, and

Reading ordinary print in newspapers.

VFQ-25

PMA reports mean scores and mean changes

FDA requested a frequency analysis for each rating within each category.

Summary of Frequency Analysis of Items # 5, 6, 7, 8 & 9

Subjects reporting extreme difficulty with the items pertaining to visual function decreased in number by one year postop.

Subjects reporting little and moderate levels of difficulty increased at one year.

It is unclear from the data reported whether some of the subjects who initially reported extreme difficulty subsequently reported moderate difficulty.

VisionCare’s Rehab Program

Implemented by the patient with assistance from the family

Professionally directed Orientation and Mobility - not provided.

LV Reading Specialist Training – not provided.

No validated methods of measuring the outcomes of training.

What is successful rehabilitation?

A reduction in the level of difficulty in performing a particular task or goal, or the reduction in the importance of that task by teaching the patient alternative strategies to achieve the goal.

Massof,RW. A system model for low vision rehabilitation. I. Basic concepts. Optom Vis Sci. 1995 Oct; 72(10): 72-36.

Is professional vision rehab necessary? Failure rate decreased from 22% to 3% with training according

to Langman et al. 1944

A survey (@ 12 and 24 months) of 200 veterans using 740 low

vision aids found that 85.4% of devices were still in use.

85.4% of 200 Veterans were found to still be using their

optical assistive devices 2 years later - Watson et al. 1997

77% of 261 cases used optical devices successfully - Van Rens et al. 1991

Improves patient independence, performance of ADLs, and

quality of life – Fletcher et al. 1991, 1994

VISUAL LOSS AND FALLS

Nevitt et al reported a threefold risk for multiple falls with poor vision.

• 25% to 35% annually of older persons fall• >40% result in hospitalization.

Beaver Dam Eye Study

– ≥60 years of age• 11% (943) of 2365 with acuity < 20/25• 4.4% with normal visual acuity had experienced a

fall in the prior year.

Adverse events - Falls

8 non-ocular adverse events 8 non-ocular adverse events occurred during this trialoccurred during this trial

Effects of Magnification

magnification alters proprioceptive senses: – judgment of relative distances – location objects in the visual space – ability to walk and to read – judgment of depth of steps and curbs

Central & Peripheral Vision

IMT implanted eyes – CentralFellow eye – Peripheral

No direct performance measures for shifting binocular suppression from one eye to the other.

Binocular Performance

Non-correspondence of overlapping fields forces binocular rivalry and suppression

Severe visual field restriction in the (dominant) IMT eye

Motion discrepancies in magnified and unmagnified fields

Possible suppression of entire fellow eye

Normal Monocular Field (OD)

Inferior

Superior

Left Right

10°

20°

30°

40°

50°

60°

70°

80°

90°

Normal Monocular Field (OS)

Inferior

Superior

Left Right

10°

20°

30°

40°

50°

60°

70°

80°

90°

Normal Binocular Field

Inferior

Superior

Left Right

10°

20°

30°

40°

50°

60°

70°

80°

90°

Binocular Field for Macular Degeneration Patients

Inferior

Superior

Left Right

10°

20°

30°

40°

50°

60°

70°

80°

90°

SC

Subjective Field of IMT Eye

Inferior

Superior

Left Right

10°

20°

30°

40°

50°

60°

70°

80°

90°

SC

Objective Field of IMT Eye

Inferior

Superior

Left Right

10°

20°

30°

40°

50°

60°

70°

80°

90°

Monocular Field - Fellow Eye

Inferior

Superior

Left Right

10°

20°

30°

40°

50°

60°

70°

80°

90°

SC

Objective IMT Binocular Field

Inferior

Superior

Left Right

10°

20°

30°

40°

50°

60°

70°

80°

90°

IMT Objective Binocular Field Fellow Eye Overlap Suppressed

Inferior

Superior

Left Right

10°

20°

30°

40°

50°

60°

70°

80°

90°

Motion Discrepancies Magnified/ Unmagnified Fields

Object motionHead motionConsensual eye movementsMotion through the environment

No symptoms were reported for IMT subjects.

Suggests suppression – the IMT image, or – the entire fellow eye image.

IMT Binocular Field with Entire Fellow Eye Suppressed

Inferior

Superior

Left Right

10°

20°

30°

40°

50°

60°

70°

80°

90°

Risks vs. Benefits

The discussion of this device warrants careful

consideration of the reported improvements in visual

acuity with respect to the postoperative risks of ECD

loss, potential perceptual adjustment problems and

unknown problems with examination and treatment of

an IMT implanted eye. .