ome individuals have had the temerity to reference the Duke ‘study’ of PNT as significant and supporting their contention that PNT is suspect. This includes QuackWatch which went so far as to publish a warning on the procedure. Some have defended the study by claiming that a place as prestigious as Duke couldn't possibly have a hidden agenda. My only response to that naive statement is that it doesn't merit comment. The facts of the matter (including their own words — see below) — in any event — are at odds with Duke's position. One has to wonder why such a ‘study’ would even be presented.

The required study protocol

In the Spring of 1997, the Duke glaucoma group were contracted to perform a study on behalf of Coronado Industries. The protocol for the study called for the following:

• recruitment of a minimum of 20 patients with POAG
• the pre-treatment IOP was to be 20 mm Hg
• two PNT treatments — 7 days apart
• complete study within 1 year
• one year follow-up
• timely progress reports

Duke agreed to this protocol.

Duke's Version of the Protocol

• recruited 8 patients at 1 year — 4 of these were faculty members
• the pre-treatment IOP was 16-18 mm Hg
• only one PNT treatment was done
• didn't start the study until after 1 year had passed
• only did a 3 month follow up
• results submitted to Coronado in 1999

Data actually gathered by Duke

 

Subject (treated) eye	Number of medications Treated (untreated) eye
JW (OD)	1 (1)
WM (OD)	1 (1)
AM (OD)	4 (4)
AR (OS)	4 (4)
DR (OD)	3 (0)
WH (OS)	2 (2)
FM (OS)	1 (1)
EH (OD)	4 (4)

 

IOP Pre- and Post-treatment
PNT eye	Pre-PNT		Post-PNT		1 day		1 week		1 month		3 months
	PNT	ctrl	PNT	ctrl	PNT	ctrl	PNT	ctrl	PNT	ctrl	PNT
JW (OD)	18	18	16	13	21	17	22	11	27	14	25
WM (OD)	16	16	14	17	20	20	18	16	18	19	16
FM (OS)	18	19	21	16	14	16	15	-	17	-	16
WH (OS)	17	19	17	18	16	15	17	18	20	20	21
DR (OD)	17	13	18	*	19	14	16	15	17	16	17
AM (OD)	24	24	24	24	26	26	25	27	23	24	24
AR (OS)	21	17	16	15	16	15	17	16	20	18	17
EH (OD)	19	19	18	19	18	19	15	14	17	17	17
Mean IOP	18.8	18.1	18.0	17.4	18.8	17.8	18.1	16.8	20.3	18.3	18.4

Conclusion(s) of the Duke Group

• procedure ineffectual because all IOP's had returned to pre-treatment levels at 3 months

• one PNT treatment is not effective — most IOP's in such cases will return to pre-treatment levels by 3 months requiring a re-treatment
• effect is greater with pre-treatment IOP's greater than 20 mm Hg
• no adverse effects, VF changes, intraocular hemorrhages, etc were seen in the preliminary studies at 1+ years

Their explanation (read excuse) was 3-fold:

1. couldn't get enough interested patients [1]
2. concerned about damaging the retina — Quote: 'after all, glaucoma eyes are susceptible to increases in IOP' — hence didn't re-treat [2]
3. ditto excuse for not recruiting eyes with higher IOP's [3] Du'oh!

Comment by item

[1] I recruited more than 300 patients within a 12 month period when I first began my study of this procedure.

[2] a conclusion/prejudice not supported by my experience nor in the medical literature; in short: glaucoma eyes are not endangered by short-term elevations of IOP.

[3] whilst eyes with sustained high IOP's show greater and more rapid VF changes over time — they are no more vulnerable to short-term IOP elevations than the others. As an aside — some eyes with OHT have IOP's approaching 25 mm Hg or more without signs of retinal damage over time.

Additionally: here's a verbatim comment by the chap who supervised the Duke Group PNT Study:

‘Our study was unable to detect a clinically significant reduction in intraocular pressure or increase in outflow facility after treatment with PNT^TM during the 3-month follow up period. However, there was a small but significant increase in outflow facility at week 1. Importantly, during the peri-operative period and the subsequent 3-month follow-up period, no significant morbidity was encountered.

It is not clear why we failed to demonstrate an effect from PNT treatment. It is possible that our sample size was insufficient to detect a small IOP reduction.

Additionally, a relatively low baseline IOP may have been a factor. Reports on PNT treatment by other investigators suggest that patients taking fewer glaucoma medications (1-2) respond more favorably than those taking more (3-4). Half of these patients (4 of 8) were taking 3 or more topical medications.

Argon laser trabeculoplasty (ALT) is a therapeutic modality that has been shown to be effective in the treatment of many open angle glaucomas. However, ALT loses effect over time, is associated with IOP spikes and other adverse effects, and the number of re-treatments are limited. A safe, relatively non-invasive procedure to reduce IOP that could be repeated could potentially be a significant advance in glaucoma treatment.

PNT offers a relatively safe alternative to ALT. Additional studies examining the efficacy of PNT using varying treatment parameters and patient characteristics are felt to be warranted.’

For some reason — no notice was taken of the fact that in the first 4 patients, the IOP dropped significantly in the first few weeks. Dr. LiVecchi performed those first 4 eyes at Duke. Could this mean that the Duke Group was ... ah ... inept?

To be fair — not necessarily. When I demonstrated the procedure in China and Italy, the doctors who followed me had difficulty in getting good adherence of the ring to the eye at first — I had to lay hands on their hands. In the Italian Study (sponsored by Novartis), the doctors there insisted that I perform the first few cases and also requested my presence for each following treatment to insure that it was done correctly. More on this latter study when the results are released by Novartis/Ciba.

I'm not excited about the measured increased facility of outflow even though such an increase is a good thing. Why? Because in our study of more than 600 eyes the increase in facility of outflow was not correlated with the IOP. That is, even in the face of an increased facility of outflow, in some cases the measured IOP may not have gone down proportionatly or at all. This is because the method used to measure facility of outflow is known to be unreliable and — as a consequence — not very useful in studying glaucoma.

As to the eight patient cohort, I know of no biostatistician worth his/her salt that would agree that a sample that small will produce any meaningful data. Nor did that notion go over very well when presented at ARVO.

Point to ponder: the FDA wants a sub-study of a group of patients who undergo only a single PNT treatment. More-or-less tongue-in-cheek, I suggested that they accept the ‘statistically significant’ Duke cohort of eight patients as proof that an additional study was unnecessary. They said: ‘Surely you jest’, or words to that effect. I wonder why? And I wonder why no one will publish the Duke report?

I rest my case. The next sections show data gathered more scientifically and with statistically valid cohorts.