What drew you to age-related macular degeneration (AMD)?

News in ophthalmology : What drew you to age-related macular degeneration (AMD)?

Sitting Down With Master of macular degeneration, Philip J. Rosenfeld
Si t t ing Down Wi th 51
What drew you to age-related macular
degeneration (AMD)?

It was my background interest in
molecular biology and genetics. At Johns
Hopkins, I got both my MD and PhD
degrees at the same time – my research
focused on genetics and I had a particular
interest in the evolution of disease in
the back of the eye, and specifically,
retinal degenerations. 

I started with a
post-doctoral research fellowship at the
Massachusetts Eye and Ear Infirmary
(MEEI) working with Ted Dryja – who
was the first to clone the retinoblastoma
gene – and Eliot Berson. I fully intended
to pursue a career in retinal degeneration
and other vitreoretinal diseases, but I
was drawn to AMD, as Johanna Seddon
clued me in that it was a genetic disease.
I became fascinated with both her clinic
and her studies that looked at twins with
AMD, and this started me on the path
of AMD; the genetic and the clinical
aspects, and the realization that there
was a huge unmet need for treatments.
What do you find the most rewarding
aspect of working on clinical trials?

To this day, what I enjoy doing the
most is designing clinical trials with
appropriate endpoints and necessary
controls, so that at the end of the trial we
will get a definitive answer. I like asking
questions that no-one else is asking,
and I had always seen myself running a
laboratory and being involved with both
medical and surgical retinal diseases.
Starting at the Bascom Palmer Institute,
I quickly learned there was nothing
better than running your laboratory in
the clinic – it is an excellent way to blend
my research and clinical interests and
compliments both aspects of my career.
Any challenges throughout
your career?

With every study that I have participated
in, or designed, I have come away with a
better appreciation of what needs to get
done. In the photodynamic therapy trials
in the 1990s, I learned a tremendous
amount, and that set the groundwork
for my ability to design clinical trials
with anti-VEGF therapy. At the time,
coming up with a treatment for wet
AMD seemed like a herculean effort.
Now, focusing on dry AMD makes
focusing on wet AMD “low-hanging

” We have a huge unmet need in
dry AMD, but I think that everything
is positioning so that hopefully in the
next few years we are going to be able to
demonstrate unequivocally that there is
a treatment that can slow down disease
progression. It is a big area. If we can
stop dry AMD at an earlier stage, then
all the downstream vision loss that
occurs from both advanced late dry
macular degeneration and wet AMD
can be avoided.

What is exciting you at the moment?
Right now, I am currently working
with collaborators to develop the next
generation of OCT, swept source
OCT, and we really hope to move the
field forwards with this cutting edge

As for treatments, I still
believe in the “holy grail” of genetics
research, that is, if you identify the
genetic locus involved in the disease
and manipulate the gene product from
that locus, then you should alter disease
progression and improve outcomes. But
when we talk about complex genetic
diseases, like AMD, the question is how
we can manipulate pathways to improve
patient outcomes?

 AMD clearly looks
like a complement-mediated disease,
and I feel that complement inhibition,
or some form of complement regulation,
is going to be very, very important in
controlling macular degeneration at
some stage.

You were the first to inject off-label
Avastin into someone’s eye. How did
you feel?
It was nerve-wracking! That is why I
had to choose the right patient, where
there was really no other option as all
the approved therapies had failed. She
was a nurse, she understood the risks
– she was going blind. So we gave it a
shot, and to this day I see her, and she
is just so grateful because we were able
to preserve her vision.
What anti-VEGF dosing strategy do
you prefer – treat and extend, or as
needed (PRN)?

I consider myself to be the father of
PRN dosing, and that all came about
from the PrONTO study, which was
designed when we began to appreciate
the power of OCT as a technology
for following disease progression and
the need for re-treatment.

 But I have
evolved. What I have learned over the
years is that patients don’t really mind
injections, and they much prefer a
treatment regimen where they can avoid
coming in as frequently. So most of the
time I use the treat and extend strategy,
but I do still use PRN in some patients
who really don’t want the injection.
If you could go back to the
beginning of your career, what
would you tell yourself?

The best advice I would give myself is
to focus on the unmet needs of your
patients and be willing to pivot with
your research objectives and follow
where the data points. And this pivoting
strategy pertains to one of my favorite
sayings of “sacred cows make the best
hamburger” – always question what
someone thinks as dogma, and never be
satisfied unless the answers make sense.
After all, everyone knew antibodies
against VEGF wouldn’t be effective if
injected into the eye.

Not! An extended version of this
interview is available online.
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