PMA P030028

QUESTIONS FOR PANEL DISCUSSION

In a paired analysis, the percent change calculated between baseline and 3 years postop was -4.76% with a standard deviation of 7.8%. When analyzed by interval one can see that losses appear to be higher between the second and third postoperative years at -2.37% as compared to the interval between years one and two, -1.12%. The sponsor has presented the following endothelial cell loss data:

Overall Endothelial Cell Density Results

Cell Count Means

Least Squares Means
Visit	N	Estimate	Standard Deviation	Standard Error	95% Confidence Limits
PreOp	183	2754.2380	357.770	26.4471	2702.4020	2806.0730
6 Months	188	2747.5960	373.622	27.2492	2694.1890	2801.0040
1 Year	240	2711.3210	412.006	26.5949	2659.1960	2763.4460
2 Years	285	2680.1730	445.398	26.3831	2628.4630	2731.8830
3 Years	248	2605.2770	429.856	27.2959	2551.7780	2658.7760

Percent Change from Baseline

Least Squares Means
Visit	N	Estimate	Standard Deviation	Standard Error	95% Confidence Limits
6 Months	139	-0.0036	0.068	0.0058	-0.0149	0.0077
1 Year	134	-0.0106	0.068	0.0059	-0.0223	0.0011
2 Years	135	-0.0255	0.074	0.0064	-0.0379	-0.0130
3 Years	107	-0.0476	0.078	0.0075	-0.0623	-0.0328

Percent Change by Period

Least Squares Means
Period	N	Estimate	Standard Deviation	Standard Error	95% Confidence Limits
1Y-6M	149	-0.0117	0.062	0.0051	-0.0217	-0.0017
2Y-1Y	198	-0.0112	0.058	0.0041	-0.0192	-0.0033
3Y-2Y	216	-0.0237	0.063	0.0043	-0.0322	-0.0153
6M-BL	139	-0.0039	0.072	0.0061	-0.0158	0.0080
3y-6m	111	-0.0475	0.073	0.0069	-0.0610	-0.0341

Recount Sub-Study: All Data

Average Loss Over Time	-49.76 Cells/Year 95% CI = (-60.69, -38.83)
Projected 10 Years	2267.43
Projected 20 Years	1769.81
Projected 30 Years	1272.18

The endothelial cell loss results for the overall analysis stratified by Anterior Chamber Depth is presented in the following table:

Overall Endothelial Cell Density Results By Anterior Chamber Depth

Percent Change From Baseline

Least Squares Means
Visit	ACD	N	Estimate	Standard Deviation	Standard Error	95% Confidence Limits
6 Months	3.0 to 3.2mm	8	-0.0234	0.027	0.0095	-0.0421	-0.0048
6 Months	> 3.2 to 3.4mm	20	-0.0288	0.076	0.0171	-0.0623	0.0047
6 Months	> 3.4 to 3.9mm	67	-0.0028	0.059	0.0072	-0.0170	0.0113
6 Months	> 3.9	44	0.0113	0.062	0.0093	-0.0068	0.0295
1 Year	3.0 to 3.2mm	4	-0.0264	0.017	0.0083	-0.0428	-0.0101
1 Year	> 3.2 to 3.4mm	24	-0.0461	0.061	0.0125	-0.0705	-0.0217
1 Year	> 3.4 to 3.9mm	63	0.0031	0.065	0.0082	-0.0131	0.0192
1 Year	> 3.9	43	-0.0087	0.056	0.0085	-0.0254	0.0079
2 Years	3.0 to 3.2mm	8	-0.0076	0.037	0.0131	-0.0333	0.0182
2 Years	> 3.2 to 3.4mm	22	-0.0373	0.076	0.0163	-0.0694	-0.0053
2 Years	> 3.4 to 3.9mm	67	-0.0272	0.068	0.0083	-0.0434	-0.0110
2 Years	> 3.9	38	-0.0197	0.066	0.0107	-0.0406	0.0012
3 Years	3.0 to 3.2mm	6	-0.0916	0.024	0.0098	-0.1108	-0.0725
3 Years	> 3.2 to 3.4mm	21	-0.0572	0.073	0.016	-0.0885	-0.0259
3 Years	> 3.4 to 3.9mm	52	-0.0412	0.079	0.0109	-0.0627	-0.0198
3 Years	> 3.9	28	-0.0471	0.060	0.0113	-0.0692	-0.0249

Overall Endothelial Cell Density Results By Anterior Chamber Depth

Percent Change By Period

Least Squares Means
Period	ACD	N	Estimate	Standard Deviation	Standard Error	95% Confidence Limits
1Y-6M	3.0 to 3.2mm	7	-0.0171	0.018	0.0068	-0.0304	-0.0039
1Y-6M	> 3.2 to 3.4mm	23	-0.0187	0.060	0.0125	-0.0432	0.0058
1Y-6M	> 3.4 to 3.9mm	74	-0.0038	0.066	0.0077	-0.0190	0.0113
1Y-6M	> 3.9	45	-0.0195	0.054	0.0081	-0.0355	-0.0035
2Y-1Y	3.0 to 3.2mm	5	0.0255	0.036	0.0162	-0.0062	0.0573
2Y-1Y	> 3.2 to 3.4mm	30	-0.0046	0.055	0.0101	-0.0245	0.0152
2Y-1Y	> 3.4 to 3.9mm	100	-0.0182	0.051	0.0051	-0.0282	-0.0082
2Y-1Y	> 3.9	63	-0.0056	0.062	0.0078	-0.0210	0.0097
3Y-2Y	3.0 to 3.2mm	5	-0.0774	0.042	0.019	-0.1147	-0.0401
3Y-2Y	> 3.2 to 3.4mm	39	-0.0326	0.072	0.0115	-0.0551	-0.0100
3Y-2Y	> 3.4 to 3.9mm	116	-0.0177	0.058	0.0054	-0.0282	-0.0072
3Y-2Y	> 3.9	56	-0.0242	0.061	0.0081	-0.0401	-0.0083
6M-BL	3.0 to 3.2mm	8	-0.0344	0.048	0.017	-0.0678	-0.0010
6M-BL	> 3.2 to 3.4mm	20	-0.0302	0.110	0.0245	-0.0781	0.0178
6M-BL	> 3.4 to 3.9mm	67	0.0018	0.052	0.0064	-0.0108	0.0143
6M-BL	> 3.9	44	0.0057	0.066	0.0099	-0.0136	0.0250
3Y-6M	3.0 to 3.2mm	7	-0.0899	0.047	0.0177	-0.1246	-0.0552
3Y-6M	> 3.2 to 3.4mm	22	-0.0295	0.068	0.0145	-0.0580	-0.0010
3Y-6M	> 3.4 to 3.9mm	51	-0.0411	0.068	0.0095	-0.0597	-0.0225
3Y-6M	> 3.9	31	-0.0637	0.061	0.011	-0.0853	-0.0421

Change in ECC : Subjects with both 3 & 4 Year Follow-Up

Mean ECC at Preop = 2550

N=27

	% Loss/Gain
PreOp to 3 years	2.12%
PreOp to 4 years	0.47%
3 years to 4 years	-1.63%

Do the endothelial cell data presented above in the overall analysis, stratified

by anterior chamber depth and the extrapolations over time provide

reasonable assurance of safety of the Artisan myopia lens?

2. Do the data presented in the PMA provide reasonable assurance of safety?

3. The proposed statement of indications reads: “The reduction or elimination of myopia in adults with myopia ranging from greater than –5 to less than –20 D with less than 2D of astigmatism at the spectacle plane; Patients with documented stability of refraction for the prior 6 months, as demonstrated by a spherical equivalent change of less than or equal to 0.50D.”

Does the panel recommend any modifications to the proposed statement of indications with respect to:

a). minimum anterior chamber depth (ACD’s of <3.2 mm were excluded in the study),

b). maximum pupil size (the 2 models of Artisan are intended for patients with pupil sizes up to 5.0 mm and up to 6.0 mm); and,

c). minimum preoperative endothelial cell density? The outcomes of ECC changes reported in number 1 above could be used to determine acceptable minimum endothelial cell densities.

Do the panel members have any additional labeling recommendations?