Mr. Neil Notaroberto: Good morning. I'm Dr. Neal Notaroberto. I'm in a multi specialty practice in Louisiana

Today, my discussion will be about the functional analysis of the retina, what we consider to be the missing link in the evaluation and management of retinal disease

A quote that I had used approximately two years ago when we were evolving with macular functional testing as well as understanding the real potential value in the diagnosis and management of macular disease was that I'd specified in an interview that macular function testing offers a highly specific method of identifying the true visual function of a patient's retina which may otherwise be missed if only conventional methods are used

This really dovetails with what Alan Bird [sp], Dr. Alan Bird had mentioned on Friday at the Retinal Specialty Meeting, where we really need at this point with the treatments that are evolving something more granular, something more comprehensive to evaluate macular function. We'll go over that in just a moment

So, when we're evaluating retinal patients, we have a plethora of instruments that can measure anatomy, really elegant instrumentation. Biomicroscopy's come a long way with better optics, advanced coatings [sp] and better illumination. Optical coherence tomography, which didn't exist, you know, almost a half a decade ago has advanced tremendously from time domain to spectral [sp] domain, giving you exquisite anatomic detail

Fluorescein angiography, going from film to digital, then of course being enhanced with noise reduction and software, and auto-fluorescence - and these are fantastic anatomical instruments that can reveal anatomic changes for you

But, what do we have functionally today? We have visual acuity, something that has relatively been unchanged for almost a century and by no means can give you enough detail to assess function of the macula, in an area, in an arena where changes are measured on a more microscopic level, on a more granular level, if you may

So, is there a better way to assess visual function? Well, macular function testing. And again, Dr. Alan Bird at the meeting mentioned a variety of functional testing that could be used

But, what really can meet the criteria for us to use as clinicians that is compact, small, not only relegated to the research institutions, FDA approved, affordable, reimbursable? Well, macular function testing meets all those criteria

Not only does it overlay a high resolution image with the functional data, but it allows you to pinpoint areas of pathology easily, quantifying the quality of vision with using several metrics, which are important, as you'll see in my case studies - average threshold over a greater--larger area, threshold sensitivity in specific areas, and of course fixation stability and location, things that you--two metrics that you're not really thinking about as a clinician until it's being presented to you, and then you can use that in the evaluation of the patient's progress

So, what instrument is available today that really does that quickly, effectively? Well, the MIA [sp] happens to be one of the premier instruments to do this

It's affordable. It has the lowest learning curve. It's integrated very well in a variety of practices, we'll see

Macular function testing really, besides giving you granular data at the specific points in the macula, enables you to qualify that data by comparing threshold data with age adjusted normative values and getting you a very clean reading very quickly, giving you a patient's average threshold and fixation as being normal, suspect, abnormal. So, you can quickly see this report when you're with the patient and judge very quickly whether you need to dive deeper into that data and look at the actual values, which are also presented in a linear format that's easy to read

So, the instrument actually--the MIA offers you two different ways to acquire this data. And that--the two different ways actually work really well, dependent upon the type of practice you have or how you want to implement the use of the instrument

So, the fast test, which measures 36 points over a ten degree area, is really designed as a wellness test. It's fast, takes about 2, 2.5 minutes, it's under three minutes without any doubt

There's no insurance reimbursement because of the type of test it is. But, if you may, you could see how this could be used in certain practices as a wellness test, as a value added service where patients who are being tracked or monitored for their annual or maybe their biannual examination, they opt for this test to get a better assessment of what their vision really is

Or, you could use it like we do in one of our satellites where we know we have patients with pathology, but do we really want to run the full extended test, the expert test and not know whether that data's pertinent or not, put the patient through that and not really get reimbursed

So, the fast test allows us to look at patients, you know, who have a family history of AMD that may need further evaluation, patients over the age of 45 that are at a higher linear risk for the four leading causes of blindness in the world - cataracts, glaucoma, AMD and diabetes. Explained problems, problems with subject complaints--though their visual acuity--remember, that core standard we have is relatively normal

Diabetics, okay, where we don't have the ability to look at a non prolific diabetic retinopathy population in a very detailed manner to give feedback to the primary care doctor whether that hemoglobin A1C is well, whether there's underlying nephropathy--I mean neuropathy or retinopathy that's undetected by our current functional testing methods

And in pre-op and post-op cataract patients, which I'm about to show you, it does play a part in

The fast test gives you very quick and easy to read data in terms of fixation and macular integrity. The nice thing about this is this helps a technician--it helps you very quickly know whether you should order this test, all right, so the test can be performed when the patient is getting an evaluation for a certain macular pathology, because in this country, you need to order a test to be able to have the reimbursement and to meet the auditing criteria for CMS

So, using the fast test allows you to see if there's anything that probably needs further or extensive evaluation

So, we move onto the expert test where it's full threshold. It's designed as a medical test, has CPT code associated with it, so it's reimbursable. And not only does it give you the severity of a scotoma in a certain area, but also the extent of the visual loss, again, on a granular level

And that's the static data. Not only does it give you static data, but it also gives you dynamic data. This dynamic data will help you track changes - the evolution, the progression, regression, depending upon the treatment modalities you're using for your retina macular pathology

And the data's presented very well, easy to read with specific points, able to be analyzed with that overlay over the anatomy so you can find the areas that you're looking at very quickly. Not only that, but there's toggle switches that you can see here that allow you to toggle on and off these data points so you're not overloaded with data that you may not need such as showing the preferred retina locus or maybe removing the fixation point so you're just showing the stimuli

The follow up test again goes with the dynamic nature of this test. The dynamic nature of the test allows for the exact quantification because--and qualification, because not only the data is repeated, but it's repeated in a method using eye tracking software so the data is repeated in the exact manner, in the exact location so it's verifiable. And again, the follow up test is considered a extended--part of the extended test. So, it's CPT reimbursable

And then, the software allows you to not have to flip through pages of data to look for progression or regression. It presents it in such a way so you can see dynamically--dynamic data in a linear format for easy access and really analysis

So, in our clinic, the MIA really is an integral part because almost every because almost every patient coming through has some type of maculopathy from ischemic to idemitis to neovascular

So, we utilize the expert test, and we utilize the follow up test. The expert test, of course, help us determine functionality, and you'll see case reports on how we use that specifically. But, more importantly, the follow up test helps guide our treatment plans

So, let's go over some case studies. So, this is the first case study here. It was a patient with significant CSR, induced vision lost, metamorphopsia

Patient--you know, when a patient comes in with CSR, we, you know, we always assess the patient and, you know, give them their treatment options. We give them what the standard of care is, and then we give them what other alternative treatments are

We try to educate them, because in today's world, our patients are internet savvy, they get a lot of data. And if we're not presenting the data to them ahead of time, they may feel that we're not aware of we're not capable of delivering any modality possible

So, this patient, we asked him to wait three months. But, unfortunately, he was a crane operator. So, he needed stereopsis to be able to operate the crane. He was at risk of losing his job. He had a very short time period to get better

After two months, we decided to use micro pulse laser. This was the preoperative anatomic findings here. You can see the large area of damage

And post-operatively, the patient improved to 20/40 - still below baseline. We had some old data on the patient. He was 20/20 beforehand

Patient was upset, the patient was upset. Well, first, I should quantify that. The patient was not--was able to return as a crane operator. He was able to regain stereopsis, enough stereopsis to continue his job. Yet, he was upset because he had expected his vision to return not only to normal, but the quality of his vision to return to normal

Well, the MIA really helped us to explain to the patient and the patient's family that could have been a very difficult situation for us that, you know, the pre operative and post operative sensitivities had increased by almost two-fold, a significant increase in sensitivity

But, as you can see here, there is a decreased threshold to help illustrate to the patient why the subjective complaints, why the visual was not as sharp or a little bit more hazy than it should be. He was able to understand by the visualization of the data, and the family was able to understand why there was not a return to what he considered "normal.

We were able to also prove to the patient postoperatively that the patient's postoperative fixation was much more stable, as well. And in the end, the MIA helped us, like I said, illustrate this--these points very well, and this patient and the patient's family actually became one of our biggest proponents after we were able to educate them very well

Next patient, we have a case of a teleform dystrophy and a visually significant cataract. Patient presents as a consult for a candidate for cataract surgery from a general ophthalmologist. There are simultaneous pathologies of cataract and the teleform district

The general ophthalmologist was concerned about setting the expectations and wanting to know if the--expectations for the patient and wanted to know if the surgery would make a difference for the patient. The GO also wanted to track pre and post operative results to determine the impact of cataract extraction on this patient

So, here's the patient's fundoscopic photos. You can see a large central foviolicofuse [sp] in deposits, stage five, right eye, stage two in the left eye, no ectopic lesions noted, red free [sp] image, really unremarkable

Fluorescein angiography was typical without evidence of corneal neovascularization. You can see anatomically that, over time, over a large gradient of time, from 2009 to late 2010, the patient showed excellent stability of the retinal pigment epithelium in both eyes

Some--oh, sorry--there was some mild retinal pigment epithelial atrophy, some migration, but nothing significant

So, here you can see a decline in the left eye specifically over 11 months associated with decreased sensitivity. You can see the sensitivity decreased right here, average threshold decreasing, as well

Oh, note the visual acuities, as well. And if you track the visual acuities, you're gonna note that we have noted in our--in clinic, in practice that the threshold measurements are more sensitive over time than acuity measurements. It seems that acuity tends to trail threshold measurements

You can see after surgery how the patient improved, vision improved sensitivity improved, as well. Again, the MIA helped us initially to look at the data, and we knew that through the sensitivity data, as--we knew that through looking at the fixation, that the patient's macular status was overall pretty stable, and that the depression in threshold was mostly due to the cataract. And we were able to prove that afterwards, of course, by--after cataract distraction, the patient's vision did improve significantly

The thresholds did improve off fixation. The fixation initially allowed us to tell the general ophthalmologist that he should be successful with surgery and he should move on. It was not a macular pathologic issue

The next case is--was another consult. Patient had simultaneous multifocal intraocular lens implant with a history of AMD. The patient had subjective complaints after a successful cataract surgery. They had a history of stage one dry AMD

The patient was followed by us for high risk conversion to wet AMD due to genetic testing. You can see here, the patient with mild dry AMD changes and pretty good acuity early--oh, sorry--you can see here, the patient had mild dry AMD changes and pretty good acuity early on, very small amount of RP changes

He had--prior to cataract surgery, the patient had good thresholds. You can see thresholds on both before cataract surgery was only--was still within normal limits, not significantly depressed at all

So, the patient underwent cataract surgery in the right eye. You can see that the patient's threshold remained very well. You can also see that the--and it's not listed there, but the patient did very well with good vision - so, good vision and thresholds in the right eye while the left eye had minimally depressed thresholds, and fixation was good

So, post--oh, let me go back. Interesting to know - fixation here, again, very tight, okay? This is--this eye did not have cataract surgery yet, did not have the multifocal implant, depressed thresholds but a very good fixation

This is the eye with the multifocal implant. Thresholds were elevated, but fixation was less stable

You see the same thing here - postoperatively, intraocular lens implant, thresholds was incomplete on this test, but the main feature here is, again, fixation. Fixation was depressed

Anatomy - we thought maybe there was some macular dysfunction of the RPE, maybe some subretinal pathology. There was none - maybe a little bit of increase in choroidal thickness, but nothing with the RPE inner or outer retinal nerve layer

Sorry

And so, we decided that--we did not see any anatomic changes in the macula. The multifocal intraocular lens implant was seen as the etiology for the fixation changes and that were related to the patient's subjective complaints of suboptimal vision

Despite other metrics looking good, the patient was--on acuity measurements, was 20/20. Threshold measurements were normal. Anatomic measurements all looked normal

And yet, we could see, using the MIA, why the patient was having these subjective difficulties. And once we were able to see that, the general ophthalmologist felt that the lens implant, and agreed with us, was--because it was of diffractive type of technology was the cause of this problem, did the lens exchange in one eye and is doing much better

He had called me actually a week ago before I was able to update these slides. Patient's subjective complaint in that one eye is gone, vision's still 20/20, he has a normal monofocal implant and much happier

So, we're able to help elucidate for the general ophthalmologist using the MIA that it was not his dry AMD, which everybody would like to blame. But, we brought back the quality of the patient's life by improving their vision, by delineating and really specifying what their problem was

Another type of patient we use the MIA on--in is diabetic retinopathy. So, we're involved in a--we're very fortunate, we're involved in a diabetic retinopathy trial

So, the pharmaceutical company came to us looking for some advice on functional measurements of the macula. They had already--you know, they were already relegated to using fluorescein angiography, fundus photos, you know, and OCT. And that's really a no-brainer

But, they really wanted to assess small--and this is probably the most important case. They wanted to assess small changes on a very small level, granular level of this drug's affect on non-proliferative diabetic retinopathy

The purpose of this drug is to reverse non-proliferative diabetic retinopathy changes on a microvascular level

Visual acuity in no way, okay, is gonna be able to grade this. These patients were already 20/20, 20/25. What more--how would we reach statistical significance on that metric? It would be almost virtually impossible

We had shown them some MIA studies, some preliminary studies. They decided to use the MIA for tracking functional changes in the macular region. It was beautiful, actually

Fluorescein angiography, typically what you see with micro aneurisms, nothing too--no neovascularization. You can see stable central foveal anatomy, nothing going on here. This is one patient over a five to six month period

And here, we can see the patient's MIA test in the right and left eye. This is in February. This was their baseline MIA. We were able to look at their sensitivities again. This was baseline before the drug was given. This was a stage one mild non-proliferative diabetic retinopathy patient

And this is July. After a five month period, the drug had improved the patient's thresholds in the macula with an increase in macular sensitivity. The series of patients we ran, which were 12 patients--well, 10 after two had dropped out due to non-compliance--we were able to have enough to show statistical significant difference and an improvement in threshold based upon the MIA

There's no other way this drug could have been tested to show these changes. And again, this goes with what Dr. Bird was talking about, that these new developments coming for dry AMD, these new developments that are coming in for wet AMD, but more importantly, dry AMD and even diabetic retinopathy, we're--as clinicians, we're not gonna be able to convince a patient to undergo an intravitreal injection when they have 20/25 vision unless we show them metrics that they are actually improving. And the only way we can do this is by having more refined data, and this is how we're doing it

This just summarizes what I just said

So, the next case - brain retinal vein occlusion, post micro pulse laser. So, this patient had previous treatments on and off for recurrent edema from ischemic induced edema from a BRVO

Patient after so many injections over the years wished an alternative method of treatment due to some relative contraindications that developed. So, the patient chose a micro pulse laser

Here you can see the effects of micro pulse laser. The vision had come back to about 20/80

Well, let's look at the MIA. This MIA is not--does not correlate with this anatomic change. These MIAs are taken months before that edema had occurred. This was the baseline MIA approximately six months before that macular edema occurred

You can see the patient had, you know, fair vision and pretty good sensitivities all the way around and good fixation

After treatment was induced and we remeasured the patient, you can see here that we were able to keep the patient's sensitivity statistically the same, that the actual granular points here had not changed before and after--before--I mean, after treatments

So, why is this data important? You're saying, okay, well, you know, the patient did better, you know, anatomy looks good, you know, what's the big deal? Okay

This happens to be one of the better patients. A lot of our patients, actually, they start losing sensitivity in certain areas after retreatments.

The MIA helps us set patients' expectations of what to expect. When a patient does not do well with a BRVO for whatever reason, they have recurrent ischemia with recurrent edema, these patients are under the belief that every time they get treated, they're gonna come back to where they were. That's not really always the case

Again, the MIA gives us data that precedes visual acuity loss. So, we're able to see after each treatment if there's any loss of fovial or macular sensitivity. If that's the case, despite the vision coming back to what their baseline was or is at that time, we can tell the patient, look, there is sub--there is retinal damage on a microscopic level. There is ischemic damage that's occurring

If this continues to happen, we--you know, you're gonna start losing vision. You're actually gonna start losing your acuity

This helps guide us to maybe using other treatments, maybe non-destructive treatments or alternative treatments

And I think this is one of the last cases. This was a case of central subfoveal drusen. This is a patient referred by the general ophthalmologist before LASIK surgery. The GO wanted to set the patient's expectations appropriately due to macular pathology

They felt that there may be some asymmetry due to subfoveal pathology and that possibly that the surgery would not significantly improve them

So, he noted--we also noted, over time, there was an increase in the retinal--increase in RPEDs, retinal pigment epithelial detachments. And we needed more granular or detailed assessment of this change on the patient's function

So, you can see here, I think, very faint scattered drusen throughout. You can see them better on fluorescein angiography. You see them. They absorb the dia. You see them hyperfluorsce [sp]. You can see subretinal RPE elevations due to these drusen

And what was important about that was that there was some juxtafoveal and foveal involvement, as you see there in the right eye and juxtafoveal in the left eye

So, what we did here, we ran a MIA test on both the right and left eye and we saw that, for the most part, macular sensitivity over the entire area but specifically in the area where the patient's final acuity would be was relatively normal despite these RPE detachments

And you can see here that even after surgery, despite the increase in RPED, the threshold held steady, and the overall sensitivity was unchanged. And the left eye also remained steady. Sensitivities, again, are remaining very stable

So, we used that data--I'll go back to that real quickly here. So, we use this data, again, to help evaluate changes in pathology and also the effects or sometimes non-effects treatment have on a patient's treatment protocols for certain pathologies. Thank you very much