Glaucoma: what my doctors never told me that could have saved my vision
By Steve Kirsch
If you are being treated for glaucoma by a glaucoma specialist, yet still
losing your vision, the information on this page might save your eyesight.
As of 10/2014, my visual fields reversed and now some of the black area is
gone. Doctor said, “that’s VERY rare." What I did that caused this is I went on a ketogenic diet. Now have super low blood pressure and my blood
sugar is now under control (I had been diabetic for 7 years and nobody knew). I
think my high blood sugar caused by my diabetes was contributing to my glaucoma,
but I cannot prove this.
This page describes the vision loss in my left eye due to glaucoma. Thanks to
a dumb treatment regimen recommended by a a respected glaucoma specialist, I
have lost almost 1/4 of the vision in my left eye and it has now also affected on my
central vision (known as "fixation"). This was avoidable if you read
the information on this page.
Unfortunately, if you rely on what most ophthalmologist will tell you
and the consumer information currently being distributed by well-intentioned
organizations (such as the highly Glaucoma Research Foundation), you will remain
in the dark, and the same thing that happened to me could be happening to you
right now if you have glaucoma that is not under control.
Here's the synopsis of what I learned (and unfortunately, you will RARELY
find anyone who will tell you all this):
- If you have visual field loss, you should take serious action
IMMEDIATELY to stop it from progressing. By the time you get loss in a
visual fields test, it means you've already lost a shitload of vision
PERMANENTLY and it is now so bad it is starting to show up in tests. If you
don't believe me, get an OCT done and look at the RNFL heat map. It will
show massive vision loss. At this early stage, you can use the visual fields
and the OCT RNFL heat map to see your progress. If you continue to lose
vision, the RNFL will eventually become so sparse that the only way to track
the little vision you have left is the visual fields test.
- All vision loss test are noisy. So you have to be careful in
interpreting them, but they give you an objective measure of where you are.
Take two OCTs one right after the other and compare them and even though
they are taken at the same time, they will look different... it will look
like you just either lost or regained vision! So you have to be careful
because your eyes typically are getting worse at a slow rate and it's going
to be really hard to see such small changes over time because the tests
themselves are noisy. Even the latest OCTs that compensate for motion (and
I've tried them all) are still noisy so small changes in your vision are
hard to track. Tracking your average RNFL thickness in each quadrant seems
to be a less noisy measure of loss since these are relatively stable between
scans done at the same time. The best way to verify stability of the testing
device is on the machines measuring you so try two scans right after the
other and you'll get an appreciation for the noise level. Generally, if you
do 4 tests and take the average RNFL of all quadrants (usually the top
number on the printouts), you will get a reasonably stable value that you
can compare with other scans. DO NOT JUST TAKE ONE SCAN PER VISIT. That is
way to too noisy. It's like taking blood glucose measurements...any
individual test is within 10% of the mean so by taking several measurements,
you get the true mean value. So you'll find the same thing with RNFL
thickness measurements. About 4 measurements per visit will reduce the
- Even if you are losing your vision at a very rapid pace, it may take 3
months or more for this to overcome the measurement noise of the
instruments. That is a big reason you should move aggressively when you see
any vision loss... you'll try things and won't know for months whether it
worked or not, and in the meantime you are permanently losing vision.
- Your objective is to stop the vision loss. The only two proven ways to
do this are: 1) lower your eye pressure (IOP) and 2) avoid like the plague
any drugs that lower your blood pressure (such as Timolol and Combigan both
of which were prescribed to me by supposedly competent physicians).
- Your doctor only measures your IOP during daylight hours. He typically
just takes a single measurement and has no idea how your pressure fluctuates
over a 24 hour cycle. Lots of people have dramatically higher IOP at night
(around 5am in the morning is peak for many people). My IOP doubled at 5am
from the value taken in the doctors office at 10am. This is likely the cause
of vision loss that is "inexplicable" but nobody can really know for sure
because we have no way to measure vision loss on small time scales (of
- Unfortunately, it is not so easy for people to accurately measure IOP at
night. I did a sleep study at UCSD to find out. If you want to be safe,
assume your IOP doubles at night so even though you think it is really low
that's because you are getting reading from your doc in the daytime. Most
docs never tell you what happens at night.
- You want to ramp up the treatment to stop the vision loss ASAP. I'd go
aggressively on the eye drops since that is easy, low cost and low risk.
Then if you stop progressing you can back off. This is better than going
less aggressively and finding you are still permanently losing vision. There
is really no disadvantage to starting aggressively on drops. Unfortunately
my original glaucoma doc took a "let's try one drug" approach which is
simply terrible advice in my opinion because there is no real downside in
the triple drug combo that I'm now on (other than slight inconvenience of
doing drops 3x/day). My original doc followed the typical "standard of
care." But there are way too many examples of how the traditional standard
of care is simply wrong and stupid. Look at diabetes. The standard of care
is horrible. It will take years for the ADA to change its recommendations.
And look at the American diet. Most of the stuff they've been telling you
for decades about fat, carbs, etc. is just plain wrong. Only decades later
is this starting to get serious attention (cover story of Time on "butter"
in June 2014).
- NEVER EVER assume that the medical standard of care is what you want.
This stuff, like the medical profession in general, changes incredibly
slowly. It is really hard to change people's beliefs once they believe
something. I have diabetes and I can tell you that the standard of care is
absolutely horrible and will make your diabetes worse.
- Check for diabetes. I had diabetes for years and none of my doctors
picked it up despite the fact I had blood tests every few months for my
cancer. It's simple to test. If you ever have a random blood sugar above 140
mg/dl, you likely have diabetes. Ask a diabetic for a test strip and a new needle to
prick your finger and look at your blood sugar 1 hour after a meal
containing about 50g of refined carbs (drinking apple, orange, grape, or
other fruit juice is a good way to do this test). For normal people, their
blood sugar will move hardly at all. If you are above 140mg/dl, you're
likely in trouble. That's the simplest, cheapest way to test for diabetes. You can also have a blood test and look at A1c to see if it is
below 5.7%. If you don't pass, you should get on a low carb, high fat diet
as soon as possible (with about 70gms of protein/day) to stop your diabetes
from getting worse and keep your blood sugar under control. I'd recommend
this diet to everyone. The more carbs you consume, the more likely you will
be to develop diabetes and then you REALLY need to cut back on your carbs .
So a modest change in eating habits today by reducing your carb intake to 50gms/day or less, the more likely you will be to avoid getting
- Check your blood pressure especially at night. If it is low, this could
be your problem. In general, you want your diastolic BP - IOP >50. If it is
less than this, you will likely still have vision problems where IOP is your
worst case IOP (which could be at 4am). My BP is 75 and my IOP at 5am is
around 25 (even though it is 12 in the daytime), so 75-25 (at 5am) so I'm
just above the 50 danger mark. Note that my daytime IOP can go as low as 10
to 12, but I think it is might high nighttime IOP that is the problem.
- Starting with eyedrops is the safest and easiest approach. The best
medications are Alphagan-P (morning and afternoon, Azopt (3X/day), and
Xalatan (at bedtime). There are lots of reasons for this combo and the
timing. Alphagan lowers your blood pressure, so don't use it at night. And
it doesn't work at night either. Azopt is a great drug and works at night.
Xalatan also works at night and into the next day, but has strongest effect
within hours after you take it so that's why you want to take it at night
because your highest eye pressure will likely be at 4 or 5am in the morning.
Basically, you want to time these drugs for peak effectiveness around 4am to
6am. So that's why the regimen.
- Never assume that just because the FDA approved a drug that it will be
helpful. I had a friend on Timolol who was losing her vision. That drug
lowered her blood pressure which increases your risk of vision loss. She
switched to Lumigan (which doesn't lower your blood pressure) and no more
vision loss. I can make the same argument about Januvia for diabetes...it is
very popularly prescribed by physicians, yet there is strong evidence it
causes irreversible damage to your pancreas.
- If the three drop regimen doesn't stop your progression, then SLT
surgery is really quick and easy and you can try that.
- If that doesn't do the trick, then you can try Trabectome surgery if you
can find someone who is SKILLED at it. This is pretty effective and a lot
less problematic than trabeculectomy surgery which is the surgery of last
resort due to risk and complications.
- I use a Reichert 7cr at home that I spent about $7,000 to buy so I could
make sure my IOP is under control 24x7 so i can get up and test my eye
pressure at night. But that is likely overkill since the treatment protocol
is the same even if you don't have a home tonometer. The Reichert uses "air
puff" to measure your IOP and unlike the gold-standard Goldmann tonometer,
the Reichert corrects properly for cornea thickness (it isn't the thickness
of the cornea that matters but the elasticity and the Reichert measures
this). Some papers claim the Reichert is the more true/accurate measure of
IOP. I don't know enough to comment on that, but the papers I read were
- Bob Weinreb at UCSD is the smartest guy I know in the glaucoma space.
Because I failed a visual fields test, my optometrist suspected I had
glaucoma, and referred me to a respected glaucoma specialist. After five years
under his care, I lost nearly 1/4 of my vision in my left eye. I went to get a
second opinion and discovered two things that really surprised me: 1) I was
given drugs that not only didn't help, but probably made the problem worse and
2) I was recommend a surgery that was much more risky that safer alternatives.
Why did this happen?
- never told me that eye pressures can rise dramatically outside of office
hours and that he lacked a complete picture of what is going on,
- never told me that there are inexpensive ways (such as using an iCare
tonometer) available for me to measure my eye pressure over a 24 hour period
(and there of course wasn't an iCare tonometer I could borrow for a night to
find out what was happening)
- never had any clue what my eye pressures were outside of office hours,
- observed that I was progressing rapidly, yet my "checked in office" eye
pressures were "normal", but yet never suggested that the problem might be
that my IOP was peaking outside of office hours
- never told me that the drugs he was giving me were not effective at
night (I later learned that my eye pressure can rise nearly 3 fold to over 30 when I am asleep) and might increase the rate of progression because it might lower my
blood pressure. His drug regimen, in my case, according to one of the
world's best glaucoma doctors, was worse than giving me a placebo because Timolol can lower your blood pressure by 15 points or more (which is huge
because it impacts ocular perfusion pressure).
- never measured my blood pressure, despite putting me on Timolol
- never suggested that I should take a carbonic anhydrase
inhibitor, despite the fact that many experts believe that the best
option for controlling IOP are prostaglandin analogs and carbonic
anhydrase inhibitors (See
question of IOP).
- never mentioned to me that it may not just be the high IOP that is bad,
but also having low blood pressure and having
diurnal IOP fluctuation (normal is 3, over 4 is a red flag, and mine is
- never mentioned that there is a surgery called
that is low risk with an
success rate and a mean IOP reduction of 40% that would be appropriate
in my case to control the IOP in hopes of stopping the progression. Instead,
he suggested the more risky trabeculectomy.
Had I been given this information and effective drugs to match my IOP
pressure curve, I might not have lost the vision I did. Am I upset about the
treatment I received? Absolutely. I totally trusted this doctor due to the
opinions of other doctors. For something as serious as
your vision, it pays to do the research as soon as possible.
I have a few ideas for what might be causing my vision loss. It could very
well be combination of factors, rather than a single factor:
- High IOP at night (as high as 29)
- Low blood pressure at night (low 70s)
- Sleeping position putting pressure on the eye (if face up is baseline,
face down is +4, and on your side is +2 in the lower eye)
- Sleep apnea/CPAP mask that has high re-breathing amount leading to lower
O2 saturation. If I don't "seal" the mask perfectly, the air I breathe feels
- Waldenstrom's (may or may not impact; the number of WM patients with
glaucoma I don't think is above average)
- I have undiagnosed diabetes that spikes my blood sugar to nearly 250 (I
just found this out in May 2014, but I have been having it for years)
- Low CSF (you can have this without headaches). See
- Autoimmune disease attacking my RGCs (Marty Wax's favorite theory)
Marty Wax thinks it is anti-retinal ganglion cell antibodies that are killing
my vision related to my WM. So the following approach is suggested:
- Have Gulgun Tezel, Jeff Goldberg, and/or Ben Barres test my blood to see
if retinal ganglion cells survive. This is the shotgun approach to see if
there is anything in my blood that might be causing premature cell death of
my retinal cells.
- Have my blood analyzed by
Alan Pestronk. This can be done remotely, without a physical office visit.
Longer version of my story
- At first signs of Glaucoma, I was referred to a well respected glaucoma
specialist in my area
- The specialist never measured my pressures over a 24 hour cycle to
determine the proper medications to prescribe and to determine the severity
of the problem. He never informed me that this was possible or recommended
or that I could buy an iCare or Reichert tonometer and do it myself at home.
- The specialist prescribed medications, then halted them for 1.5 years,
then prescribed medications that were known in the literature to have no
impact at night which is when I have my highest pressures (over 30).
Furthermore, the drug combination I was prescribed (Combigan) also lowers
blood pressure which can accelerate the damage. So what I was given was
worse than a placebo...in all likelihood it actually accelerated the damage!
- Virtually all of my vision loss was during the times that I was only "no
drug" or "drugs that only work in the daytime and lower your blood pressure"
(Combigan) regimens (see fields test result below). My IOP was never
measured except during office visits. The doctor had no clue my IOP peaked
in early morning when the drugs he prescribed would have little to no
- I was then told I needed major eye surgery (trabeculectomy) if I wanted
to save my vision.
- I decided to get a second opinion.
What happened when I saw one of the world's best glaucoma doctors (Weinreb
- I was immediately switched to a drug regimen using a two drug
combination (Prostaglandin analog and carbonic anhydrase
inhibitor) each of which is shown in peer reviewed studies to be
effective at night and would be
providing the maximum impact.
- I was sent to the sleep lab to have a 24 hour IOP measurement. I
discovered that my IOP was low during waking hours, and peaked at over 30
overnight even though I was now taking two different "best in class" drugs
to lower pressure at night. I can't imagine what my pressure would be on no
medication or medications that only work in the daytime
- Because even when I was using drugs that worked at night my IOP was
still too high and my central vision was now impacted, he recommended
trabectome surgery, which is far less risky and life changing than the only
surgical option I was offered by my initial physician
- I had the surgery done and my eye pressure after the operation was 9 in the operated
My best advice to preserve your eyesight no matter who you are is this: Get a
Cirrus OCT once a year and take a look at the RNFL thickness map and track this
over time and look for changes in the color map. You'll see if you have a
problem way before you start losing your eyesight so you can stop it before it
permanently takes your vision. By the time your vision loss shows up on a
"visual fields" test, that vision is already permanently gone. So if you want
the best chance to protect your vision for the rest of your life, get an RNFL
thickness map on an annual basis and take any progression very seriously.
Six things everyone should know (that you probably
are not already aware of)
Most people have peak IOP early morning while in
bed. So the IOP your physician measures (during office hours) can be largely
irrelevant. While we know that lowering IOP slows progression, we cannot
prove yet that most of the RNFL damage is being done at night. However, this
is the most logical conclusion.
That peak IOP can be huge. I am 12.4 during the
evening and 30.5 12 hours later. Make sure you know by using an Icare or
Reichert tonometer at home (e.g., buy or get one on loan from your
The risk of disease progression within 5 years was
six times higher for patients who had a diurnal IOP range of 5.4 mm Hg than
for those with a diurnal IOP range of 3.1 mm Hg. So you want to control your
peak pressure to keep the range down.
Drugs do NOT work evenly over 24 hours. Some drugs
have virtually no impact during the night (when pressure is highest). Some
drugs work for days, others for hours. Know
the 24 hour effectiveness profile of each of your medications. You may
discover that your drugs do virtually nothing at night.
There is a bunch of data suggesting that OPP is more
important than IOP. This can't be proved yet. But if you believe it, then
drugs that lower your blood pressure (such as Timolol) are really bad for
you. If you are not sure, it may be much safer to simply to avoid drugs that
lower your blood pressure.
Get regular OCT measurements and look at the RNFL
heatmap. This will tell you if you are losing your vision. Take steps to
stop it before it starts impacting your visual fields test. Your RNFL losses
are permanent so the sooner you stop/control your progression, the better.
Try different meds to stop. If that doesn't, then do a surgery.
Trabectome, done by a skilled surgeon,
is effective 84% of the time and is much safer than trabeculectomy. 40% drop
in IOP is typical.
The average person (without glaucoma) loses about 1-2 microns in RNFL
thickness in a decade. People with glaucoma can lose >1 micron/month. So
this is a pretty good measure of progression.
Suggestions I have for glaucoma specialists
Had my doctor followed these recommendations, I would
likely not have suffered any noticeable vision loss.
It's fine try different medications, but try each
medication for a week, then look at IOP at various times against the target
IOP range objective, and if it is not achieved, try different drugs (adding
or switching). Do not leave someone on a medication without confirming that
the peak IOP was reduced by the medications. Once all medication
combinations have failed to reduce IOP, clearly explain that the
alternatives of surgery vs. further vision loss.
Offer to loan out a self tonometer (such as the
iCare) for free to patients
Offer to explain why each drug was prescribed for
the patient based
on the IOP profile and the drug diurnal profile.
If prescribing any drug that can make the glaucoma
worse, such as Timolol, clearly explain this to the patient and the
rationale for prescribing this.
If prescribing a drug regimen (such as mono therapy
Combigan) that do not work at night to address high IOP at night, clearly
explain to the patient that there is no scientific basis to believe that
that such a regimen would be effective.
Tell your patients all the viable surgical options,
even the ones you do not do, e.g., trabectome has an 84% success rate (yet
was never offered as an option for me by 2 doctors I saw).
All patients should be given a Glaucoma Information
Sheet that covers these points:
Your IOP may be much different at night. To
ensure the best outcome, we recommend you use a tonometer at home and
get a 24 hour profile.
Once vision loss shows up in fields test, that
is permanent functional vision loss. If we are effectively treating you,
the rate of loss in a fields test should be very minimal.
The best way we have right now to objectively track progression is
the OCT RNFL thickness map. Glaucoma will show up in the OCT far sooner than
it will show up in the fields test so if we are effectively treating
you, you shouldn't see much variation in this map. So treating you very
early and stopping progression as seen on the OCT can prevent any
functional vision loss and it gives us the most amount of time to study
your rate of progression and to try different drugs.
All of the drugs we give you have a very short half
life. So after you've been taking a set of drugs for a few days, we
can measure your IOP and see if we are controlling both the peaks and
the range. If not, we should switch drugs and/or add drugs until we
bring your pressure under control
It is advisable for the IOP to be relatively
stable (within 3mmHg over a 24 hour cycle). Huge swings, such as from 12
to 30, mean we have not done our job of controlling your glaucoma
Different drugs have different diurnal profiles.
Our job is to look at your IOP profile and match the drug effectiveness
profile to your IOP profile.
There are three things we can do to reduce
chance of progression: lower your peak IOP, lower the dirurnal IOP
variation, make sure you are not on a drug that might lower your blood
Certain glaucoma medications, such as beta
blockers, might make your glaucoma worse. In particular, beta blockers
can lower your blood pressure and may increase your risk of progression.
If a beta blocker is prescribed, we should carefully measure the impact
on your blood pressure to make sure it is not being lowered.
My risk factors
The key to managing glaucoma is to eliminate as many risk factors as you can
and see if
My IOP with aggressive pressure drugs has been as high as 29
at 5:30am. Only one doctor figured this out: Weinreb.
My diastolic pressure was professionally measured
during the day to be as low as 58. That is a huge risk factor. So my DPP has been <<50 at times due to high IOP
+ low diastolic blood pressure.
Waldenstrom's macroglobulinemia, but currently under
control with LBH-589 which is an HDAC inhibitor (see
Kirsch Waldenstrom's Macroglobulinemia Diary).
I don't know if the LBH-589 lowers blood pressure, but that is one of the
first things to check to see if any medication lowers blood pressure.
sleep apnea (I use CPAP every night). CPAP in
general raises IOP by a few points. This could have put me over the edge. So this may be the
difference right there. But only 1 doctor knew this!!
The way I sleep (on side) perhaps has been suggested.
Pressure increases on the side you sleep on.
My Dad had diabetes around my age
Drance heme seen before I progressed
Gülgün Tezel, M.D.: we have already run some analysis
(called SDS-PAGE of retinal proteins followed by immunoblotting to probe with
your blood) and detected some antibodies in your serum samples which reacted to
some retinal proteins. We will now run more advanced analysis (called mass
spectrometry) to identify what specific retinal proteins your blood reacted to.
I expect that this analysis may take couple more weeks. We can not simply tell
whether these serum antibodies are normal or pathogenic, but in your case, we
can determine whether they exhibit an increase or decrease in their titer over
time with any correlation to your disease progression. I bet most of these
antibodies can be found in disease-free people as well; however, in some
predisposed individuals (like yourself) they may be the last drop that spills
the cup and contribute to disease progression. In our ongoing experimental
studies using animal models, we hope to better understand when/why/how they
might be pathogenic.
Weinreb's diagnosis: OAG, i.e., open angle glaucoma. Your presentation is typical for open angle
glaucoma - progressive bilateral optic neuropathy with excavation, beta-zone parapapillary atrophy and progressive loss of retinal nerve fibers over many
months. Moreover, your optic nerve does not have pallor exrcept in areas
corresponding to loss of retinal nerve fibers. As we discussed, there is
little that is certain in medicine. Rather we make decisions based on
likelihoods. In my opinion, it is highly likely (VERY highly) that you have
open angle glaucoma. Susceptibility of optic nerve to damage enhanced by
possible risk factors including blood viscosity/oxygenation, sleep apnea/CPAP.
glaucoma aka normal tension glaucoma (NTG) from the data you showed me. does it
matter yes and no. NTG is in general harder to manage and in people under 60 one
thinks of other things that contribute i.e. Waldenstrom's.
Wax's diagnosis: auto-immune glaucoma since I have WM and people
who are prone to diseases of the immune system are more likely to develop other
autoimmune diseases. Gülgün Tezel can test for this using blood draw. Tests for
anti-retinal antibodies including those against HSP60 and HSP27 which kill RGCs.
If I have anti-retinal antibodies, treatment options are: (1) plasmapheresis
(expensive and insurance won't cover, but lasts for 3 months), (2) chemo drugs
like cytoxan (but horrible side effects), and (3) drugs such as novel agents
such as Rituxan, Velcade, etc. (perhaps even TNF alpha
inhibitors such as Enbrel, Remicade or Humira which may be useful against WM).
Franz Grus in Germany can also do this test.
Note: Normal pressure glaucoma (often
inappropriately called "low tension" or "normal tension" glaucoma) is actually a
glaucoma with open angles, so it is technically a form of open angle glaucoma.
My game plan
Take full baselines measurements (sleep, triggerfish, OCTs, STARFISH study,
Spectralis scan, etc). Weinreb is really the “man with all the toys” here. I
was very impressed with his setup in San Diego and his team.
The sleep study showed that even after using Zioptan and
Azopt, my pressures are way too high at night. So do trabectome for left eye.
Risks: 16% of the time it doesn't work. It generally lowers pressure around
40%. You can get
post operative pressure spike right afterwards (within 24 hours which is why
they have you stay in the area overnight). May need express shunt or other
measure if that happens
I would like to try different drops, e.g., Lumigan, to see if there is any
measurable difference in IOP (absolute drop and/or daily variation). Weinreb
says all the PG analogs are pretty much the same and the Lumigan data could
be just marketing hype.
Get a Reichert 7CR to track pressure
at home. Measure impact of dosing at different times, using different
drugs, impact of exercise, CPAP, and stopping my cancer medications.
Separately, I think there is huge low hanging fruit here with
OCT data if we can make it repeatable. If we can take it so two OCTs can "line up," then we can see
progression in a month or less. The Spectralis OCT (with TruTrack) and the
latest Cirrus 6.5 software (with FastTrac)
align things better
and should give more repeatable measurements that can be used for tracking
progression. Unfortunately, I did 3 scans with the FastTrac, and they
weren't repeatable. So nothing has achieved repeatability yet. Solve this and it
The Spectralis will only do a B-scan when the eye is looking
at the dot. The Cirrus doesn't use a dot and instead takes the images and lines
them up. Since your eye is moving and your IOP is constantly changing, the data is noisy. If you took repeated A-scans in
the exact same area, some will match up, but not all. This is due to eye
movement as well as surface thickness variation since the heart and blinking is
constantly changing your eye pressure. Your eye can move a few microns
or a pressure change can mess things up. You can't even do A-scans in the
exact same place and get the same value. So the
problem is simple: Once you can do two A-scans in the same spot and get
the same data every time, that is the key breakthrough. Everyone agrees that such data be transformative.
Because then you can measure progression on a small timescale to see what is
working and what is not. You should use the full 2D RNFL thickness heatmap, and
look for pattern changes, and not just the circle. This gives you the greatest
The typical standard of care is: whoops, you failed visuals fields. Sorry
that means your vision is gone forever in those area. try this medication protocol, come back in
a month and if IOP is still high, we can try different drugs (even though
the results of those medicines are mostly known in less than a week).
However, we'll measure you during office hours rather than at 5:30am which
is when a lot of people peak, so I'm sorry but the measurement may be not so
meaningful. So hopefully we guessed right. Because if we
didn't, it's surgery for you.
Based on what we know today, if you want the best chance of stopping vision
loss, what we really should be doing is 24 hour IOP measurements and blood
pressure measurements and keeping your IOP low and stable and
keep the DPP (Diastolic – IOP) over 50 at all times.
also try different drops to see which are the most effective in their body.
Doing something as simple as switching from one eyedrop to
another has been know to completely stop progression.
an OCT regularly would also help. Standard practice is to wait for the vision to
show in a fields test. But by then, it’s too late. You can see glaucoma
coming a country mile away with an OCT and that is the time changes are MUCH
easier to measure too because there is more “signal." Had I known what I
know now, I would have done this.
I know there are practical reasons like insurance reimbursements and false
positives that are the reasons why we do it the way we do today. This is a
original doctor who came highly recommended to me, gave me Combigan. There
is credible data showing that this was worse than a placebo (see notes on
Combigan below). So if we can't educate doctors on the diurnal curve of the
various medications, at least we should be able to educate the patients.
My current advisors:
- Dr. Andrew Iwach, glaucoma specialist (San Francisco, CA)
- Dr. Maureen Hanley (Boston, MA)
- Dr. Robert Weinreb, glaucoma specialist (San Diego, CA)
Other doctors I've consulted or plan to consult:
Alon Harris at IU has ocular blood flow testing equipment.
Cantor at IU is in year 4 of a 5 year study for OPP.
Dr. Katz at Wills
Eye Institute (Philadelphia)
Tests that you can do:
- sleep study w and w/o CPAP
- 24 hour IOP
- STARFISH study
- blood test for genetic marker
- MRI thickness of optic nerve (CSF indicator)
like to look at raw spectralis OCT data and discuss in more detail with someone.
- ORA: Corneal hysteresis (CH) measurement. A low CH is correlated with
- Can I get a doppler imaging blood flow baseline measurement so I can
quantify my OPP? Yes, but company couldn't get reimbursement so couldn't
sell machine. They can do it on OCT. Not normal part of the test since no
reimburse. Not usually part of research protocol either. Using optivue.
- How can we get repeatability of A-scans in the same place? When the eye
is in the same position, the measurements are repeatable. But the problem is
the eye moves. So is there a way to measure the RNFL map in a person, wait
60 seconds, and be able to align the second scan on top of the first and get
sub-1um differences in thickness for most all spots?
- When you take new eye drops, how long does it normally take to get to
IOP equilibrium (i.e., relatively repeatable diurnal IOP measurements)? 1
week? A few days? does it depend on the medication? A: generally a few days.
- If you understand your diurnal IOP variations, can you dose optimize
your medications? i.e., is there a known diurnal efficacy curve for each
medication? or is the diurnal curve for each med different in each patient?
A: each med has a unique dirurnal curve and the curve on day 2 is different
than on day 1 if it is a long lasting drug.
- We've known for over 20 years that
tonometry is accurate and beneficial. What is the current best
instrument for this? the Reichert
PT100 or the
Pulsair intelliPuff Tonometer? The
found to be just as accurate as the Goldmann (.3mmHg mean difference) if
you have pressures in the normal range (like me). Or something simple that
uses contact like the Tono-Pen AVIA® Applanation Tonometer or the Perkins
Mk3. Maureen likes the Perkins Mk3 and it is pretty cheap (about $1500). Or
through the eyelid using a Diaton tonometer ($2750). Or the
The iCare lets you take measurements yourself and attaches to a PC. No drops
and no air! In the US you can only buy the original ICare for
Fiteyes website recommends the
Reichert 7CR ($8,200)
and specifically now
does not recommend
the iCare One (although he likes the iCare Pro version which appears
One requires user skill, unlike the Reichert. iCare guy will come train
you he's at 916-208-5784. The Reichert guy will hand deliver the unit for me
to check out and he'll beat the $8,000 price. A: I went with the Reichert
because it is fast, easy, no operator error, and very accurate.
- I've read that you can have progression in visual fields with no change
in the OCT. is that really true? A: yes, but only if it is a central nervous
system problem. So it is rarely true. .
- do the med frequencies make sense? e.g., morning and noon for
Brimonidine ? A: yes, because Brimonidine doesn't work at night.
- is it better to space 3X/day drops 8 hours between doses? or morn, noon,
evening which biases to waking hours? 8 hours between. 3 minutes. then wait
5 min. A: You should space it to keep your IOP stable, but generally 8 hours
- is dose/response curve optimized for the 3 drugs? A: ideally, but I was
given prescription before the sleep study.
- should i pinch nose or just don't blink? A: pinch your nose only for
drugs which may have a systemic impact, e.g., brimonidine.
- 3 min close or 5 min? A: keep your eyes closed for 2 to 3 minutes.
- 5 minutes between instill even if close eyes for 5 minutes? A: give it
at least 5 minutes after you open your eyes.
optic nerve stimulation? A: nobody has ever heard of it.
- repeatability of OCT measures and looking for fast changing areas? A:
people are working on this.
Learnings from patients:
Different drugs have different
IOP lowering profiles.
All drugs are not alike and you should test them on you (e.g., Lumigan is
reported to work really well in some cases)
Timolol put in your eyes may
lower your diastolic blood pressure in some people and that will adversely
affect OPP which is an important factor. See
Clinical Update: Glaucoma.
- Patients have reported
a high correlation between OPP and the damage that was noted via
tests. Making sure that OPP=diastolic - IOP is >50 is a good strategy
for minimizing damage. So lower your IOP and do not do anything to lower
your blood pressure is a good strategy.
Every patient with
glaucoma is different and what worked for one patient doesn't necessary work
for another. The fact that a patient's glaucoma has been stable
for one year or more does not necessarily mean it will remain stable. Glaucoma
progression is often not linear but can occur in spurts, so you need a longer
time frame than one year to determine whether stability has truly been
A patient in Japan reported low CSF leakage causing
vision loss in two cases from an unusual cause:
In the year 2000 I had survived a massive brain
hemorrhage, after which I was implanted a vp shunt system. The pressure of
the valve was originally set at 70mmH2O, but never changed . Last year, when
I was desperately visiting doctors for help a neurosurgeon, looking at my
head CT image, said there was nothing wrong with my head, but also said that
maybe the VP-shunt system was overdraining...At that time I didn't give so
much importance to those words but later my husband found the blog of a
Japanese man who had a similar case and was almost completely blind (failure
of drops, SLT, trabeculectomy...) and doctors recently found out that he had
had a car accident in the past and the CSF kept on leaking all those years
from his spinal cord, causing a lowering of the CSP...Now it seems he is not
losing his sight anymore, thanks to a cure called "blood patch" to stop the
fluid coming out.
drug category that can cause or exacerbate glaucoma is steroids such as
cortisone or prednisone. These are commonly used to treat many clinical
- To asses, use average RNFL thickness (early to moderate). use visual
fields after that. Can use both.
- 90% to 95% of patients will stop progressing if we lower the pressure. If that
doesn't work, you are in the 10% "hard to treat" category.
- IOP can vary greatly throughout the day and depends on what you are
doing. So lifting weights can lower your IOP and thinking can raise it. You
can see a 2:1 variance over the day. See
- It isn't your absolute DOPP that matters, but your change from baseline
(before you had glaucoma). So the DBP-IOP>50 is just a guide. Your actual
threshold number may vary from this.
- For self measurement, the Reichert 7CR seems like a safe choice since it
is easy to line you up for a perfect measurement. It also gives a confidence
score that the measurement is accurate. The problem with the portable
instruments is alignment. You get it wrong, you'll have inaccurate results.
Even smart people who have been trained, often get it wrong with a portable
- Stress and the Valsava maneuver can increase IOP. Exercise seems to
lower it, but weight lifting with heavy weights can raise it.
- Sleeping on one side can raise the IOP on the side you are sleeping on.
- Get a self tonometer like the Reichert 7CR or the Icare tonometer. Then
you can easily try different eye medications and see the impact so you can
optimize the dosing and timing.
- Tips for dosing experiments: From baseline, if you take a drug,
it generally will reach maximum effectiveness after 6 to 8 hours. It will
then slowly decline back to baseline over a period of 2 to 3 days. So you
can stop your drugs for a few days, measure your baseline, then add a drug
and see the effect in your body. Pay attention to how well it controls the
IOP peaks since that is where the problems are. Also, re-measure after 4 to
6 weeks because a drug that appears to work at first in the first week or
two, can have much lower effectiveness after you've been taking it for 4
weeks. If you are on a drug combination, you can try stopping and starting
the drug and seeing the impact. You can also experiment with changing the
time of day. CAUTION: your IOP has a diurnal cycle, so you need to make
baseline measurements and then look at your deviation from the baseline
diurnal curve, and not from a single measurement. One way to do this is to
always take measurements at the very same time each day, e.g., when you get
up in the morning which in many cases will be a high point.
- For many people, your highest IOP pressures are generally while you are
asleep, or very early in the morning. So it is often the case that all the damage you are doing might be all done at night or
first thing in the morning when your IOP is high and blood pressure is low.
and reliability of candidate tonometers for measuring intraocular pressure
reveals that Non contact tonometers are virtually the same accuracy as
GAT...within 0.24mmHg (see Figure 28). Doctors still cling to the belief
that non-contact tonometers aren't accurate though.
- Get your IOP and blood pressure measured over a 24 hour cycle so you can
see where your peaks and valley are.
- The safe zone is when at all times your diastolic blood pressure minus
your IOP is always >50.
- If you are progressing, test different drugs, even when your physician
says that they are the same. Different people react differently. Studies
show that Lumigan is the same as other drugs, but smart physicians know that
Lumigan can be slightly more effective in some people and not others. So get
those "samples" from you eye doctor and change every week and measure at the
end of the week. Find out what works for you. This simple advice may be able
to save you a surgery. This is not theory, it is fact based on real patients
who switch drugs and their progression stops cold.
- If you are progressing fast, you can see a 3um average thickness delta
in just 3 months. If you are normal, you'll lose about .2um or so per year.
Patients can lose
7um/yr in the inferior region (as in the patient in the Zeiss datasheet on
how to read an OCT). Note that this is a 3.5um overall loss, but by
limiting the averaging to a narrower region (the inferior region), you can
see much greater average change because the thickness change is NOT
uniformly distributed in glaucoma (most people will lose the inferior region
first; i lost my temporal inferior region first, for example).
- patients with low CH should undergo more careful surveillance in search
for past VF progression. Lower CH could, therefore, be (1) a marker of
increased susceptibility of the optic disc to glaucomatous damage, or (2)
may be the result of glaucomatous damage itself.
- Minimum detectable change has to be 5um or more to "see" it on an OCT
right now due to the noise in the positioning when they make the
measurements. I agree with that. That's what I found on test data. The paper
Test–retest variability in structural parameters measured with glaucoma
imaging devices concludes "Although SD-OCT systems may be currently
prevailing because of the volume of information provided and the relatively
better test–retest variability, these systems need improvement in their
test–retest variability measurement capabilities." This is really the key to
- When a neuron dies, it goes fast. A single neuron can go from alive to
dead in 1 hour.
- when a neuron undergoes apoptosis (which is really fast and can happen
over an hour), the axon dies at the same time and shrinks over 24 hours.
Since average nerve fiber thickness is 80um and a dead eye is <40um, one can
imagine that the shrinkage is close to 50% in living tissue. This is
(by how much and over what period of time).
- Blood pressure seems to jump around, part of it is you blood pressure
normally will vary quite a bit, but there can be variance in the skill of
the person taking it. The computerized devices can sometimes exactly match
the manual blood pressure readings, and other times I've seen it be 80
- Always talk to >1 doctor. I've learned different and very valuable
things from each doctor.
- Both ends of blood pressure (too high systolic or too low diastolic) can
damage the optic nerve.
- See your eye doctor regularly and get a visual fields every time at
However, an OCT will reveal loss MUCH sooner than visual fields so I highly
recommend this test for everyone. Once it shows up in a visual fields test,
your vision is permanently lost.
- My field loss likely originated from
ischemic optic neuropathy from the Rituxan treatment of my blood cancer that
caused an elevated IgM. The doctor at Stanford did not read the test results
for 1 week. Had she read the test when it came in, I might not have had any
vision loss. Learning: make sure your physician (or you) is reading your
tests as soon as they come in.
- Take any visual field loss very seriously. If it progresses faster than
"normal" take action immediately. Understand what those field tests mean,
and keep a careful eye on how fast you are degrading. If you are degrading,
try alternatives ASAP to HALT it. What happened with me is the doctor
basically only wanted to do the trabeculectomy as a last resort which is
right since it can cause cataracts and increase your eye pressure or lower
it too low. So we tried drugs. But the drugs didn't lower the IOP that much,
either because it was the wrong medications for me, I didn't keep my eyes
closed long enough, I pinched my nose, or whatever. So he just stood by as I
declined because the "cure" (the surgery) can make things worse. Had I
changed the way I administered the drugs and taken the right drugs, this
decline might have been avoided.
- Switching eye medications to drugs I take 3 times a day (see below) and
simply keeping my eyes closed for a solid 5 minutes after each drop (no
pinching like they tell you because that can make things worse) caused a
dramatic and immediate difference in my IOP (from 16 to 12). This apparently
is not well know since Dr. Tayeri still doesn't believe it.
- The SLT laser surgery further reduced my IOP from 12 to 10
- I have loss in just one quadrant of my left eye and it respects the
quadrant boundary. This suggests it might not be glaucoma but could be
neurological. The way to rule that out is an MRI of the eye and brain
(orbital and brain MRI).
Could be a
problem In the chiasm behind the eye. But my symptoms were not
consistent with a neurological cause, so I skipped the test.
- It is helpful to know my IOP and blood pressure during the night. This
can be done either with a technician using a Perkins Mk3 hand-held tonometer.
If the high IOP is happening at night, we can adjust medications, etc.
For my vision loss, doing a 10-2 field (76 points
over 10 degrees) instead of 30-2 (76 points over 30 degrees) will give a
clear indication the extent of the damage.
If your loss is only in one eye and one quadrant like
mine, it may very well be neurological.
Unilateral glaucoma is usually trauma, artery
Dr Tayeri points out that the Shiley Eye Center in
San Diego has a sleep lab where they did a lot of research on night time IOP.
I don't know whether they offer clinical IOP measurement services to private
patients, but it might be worth asking. The Shiley Center is also where they
clinical trials on the triggerfish contact lens that measures IOP for 24
Patients who are more prone to low tension glaucoma
(where the IOP is normal but you have vision loss) include patients who have
systemic hypotension, anemia, cardiovascular problems, and sleep apnea. High
serum viscosity (SV) also appears to be a risk factor.
- There are things that can possibly exacerbate the problem so you should
measure them to see where you are:
- High IgM/serum viscosity
- Low hematocrit (HCT), e.g., under 32
- Low diastolic blood pressure (50 or lower)
- Your medications (e.g., for cancer)
- CPAP (can increase IOP)
- Sleep (because IOP rises at night)
- Neurologic damage (such as a tumor in your brain or behind the eye
impinging on the optic nerve)
- Sleep apnea is a risk factor low-tension glaucoma.
- How you sleep (head raised on pillow is best)
- To measure your IOP during the night, do not get up. Have a technician
from a nursing home come to your home and use a hand-held Perkins Mk3 to
measure eye pressure.
- To measure your blood pressure at night, wake up and take it while you
are lying down. Low diastolic blood pressure is common in people with
- New medications may work at first, but may not continue to be effective
- On my optic nerve photos one shows a Drance Heme. These are common for
low tension glaucoma.
research has shown a high incidence of glaucoma and worse glaucoma on the
side you sleep on
(right eye) and 578 (left eye) cornea thickness which is thicker than
normal, which indirectly means your IOP is a few points lower than what is
Paper by Caulkins shows p38 inhibition can prevent distal axonopathy. In
terms of p38 inhibitors for FDA approved indications, doramapimod is
generically available, used for arthritis. But honestly, more work in animal
models is needed to prove efficacy and safety for eyes -- and to test the
FAR more potent experimental versions. However, right now we can ask on
arthritis groups as well as glucoma groups to find patients who have both
and see if anyone is taking doramapimod or any other p38 inhibitor (such as
VX-702) for rheumatoid arthritis. The drug they used targets mostly the
alpha isoform. According to
Inhibition of p38: Has the Fat Lady Sung? (Feb 2009) more
than 100 p38 MAPK inhibitors have been developed for the potential treatment
of inflammatory and/or cardiovascular diseases, but the majority have been
discontinued mainly due to undesirable side effects. VX-702, one of a series
of second-generation, orally active p38 MAPK inhibitors, is under
development by Vertex Pharmaceuticals Inc in collaboration with Kissei
Pharmaceutical Co Ltd, for the potential treatment of inflammation, RA and
cardiovascular diseases. Preliminary phase II results for the treatment of
RA and ACS have been reported recently. One previously heralded agent,
doramapimod (BIRB796), was thoughtfully studied in RA, Crohn’s disease, and
psoriasis. It wasn't effective. Ultimately, development of this drug was
terminated because of the development of liver function abnormalities. The
implications of this are unfortunate because it means finding someone with
arthritis and glaucoma who is taking a p38 systemic inhibitor is likely to
yield nothing. So much for the "free" clinical trial data.
There are a number of very interesting and potentially
effective neuroprotective agents for glaucoma that are being studied in our
laboratories (eg CNTF, sirtuins, HDAC inhibitors, memantine). Very often
what works in the laboratory, such as the Novartis compound tested by
Calkins, is promising, but does not make it into clinical trials.
anti-oxidants like alpha lipoic acid might help.
- Ben Barres at Stanford: We
are making the first inhibitors to a part of the immune system called the
classical complement cascade, as my lab discovered that this pathway is
killing synapses not only in the normal developing brain but gets
reactivated early in neurodegenerative diseases that involve massive synapse
loss including Alzheimers and glaucoma (in fact we published a paper not so
long ago showing that inhibition of this pathway is very powerfully
neuroprotective in a mouse model of glaucoma). We've already succeeded in
making the first therapeutic monoclonal antibodies to the classical
complement cascade and shown that these powerfully inhibit this cascade,
both in mice and humans. And we have very exciting data showing that these
antibodies completely block the disease process in two different
neurological disease models involving the actual human pathological
antibodies including neuromyelitis optica (a devastating form of MS) and
Guillain-Barre Syndrome (an often severe form of peripheral neuropathy). We
are testing them in several neurodegenerative disease models now and will
soon have that data too (preliminarily that is looking very exciting). I
strongly believe that this will be the first treatment that blocks
neurodegeneration in Alzheimers disease which is our primary interest (as
you know the recent trials with antibodies against amyloid have all failed
in humans with Alzheimers).
- John Flanagan wrote an
article "Both Sides Now: CSF and the Development of Glaucoma" that talks
about the importance of OPP and CSF. The clinical relevance of these
observations is limited by the invasive nature of CSF pressure measurement,
which currently requires a lumbar puncture. Innovative research is being
conducted to identify non-invasive ways to assess CSF pressure. One of these
may be as simple as a measurement taken in the ear. Of course, manipulating
CSF pressure may be inadvisable for reasons of systemic health. But
identifying patients at risk of glaucoma and progression by assessing
translaminar pressure differences may tell us which patients require the
most aggressive IOP reduction to protect the optic nerve and prevent visual
dysfunction in glaucoma.
- Neuro-ophthalmologists are
rare: Kim Cockerham, Richard Imes, M.D. here in San Francisco, another
specialist in Los Gatos (Dr. Iwach knows him), and Joyce Liao at Stanford.
Kinase in Axotomy-Induced
Apoptosis of Rat Retinal Ganglion Cells (2000) points out p38 inhibitors could be potentially useful for the treatment of optic nerve
trauma and neurodegenerative diseases that affect RGCs, such as glaucoma. So
very relevant in my case.
fluid (CSF) pressure is lower in glaucoma patients; so is diastolic blood
pressure taken at night in the supine position; and IOP is higher. OPP
(which is blood pressure - IOP) has been measured in NTG patients is
significantly lower than in the control group. SOURCE: Ramli N, Nurull BS,
Hairi NN, Mimiwati Z. Low nocturnal ocular perfusion pressure as a risk
factor for normal tension glaucoma. Prev Med. 2013;57 Suppl:S47–9.
Trans-laminar pressure difference (IOP-CSF) is least favorable at night as
well. (See Both Sides Now: CSF and the Development of Glaucoma, John
Flanagan, Ph.D., M.C.Optom ).
transplantation is in the realm of possibility in the next 10 or more
years. andy huberman (CFC2 group now), a previous postdoc in Barres' lab,
now in his own lab at UCSD, has shown that retinal ganglion cells that are
coaxed to grow down the optic nerve will then enter the brain and find their
correct visual neuron targets and reconnect with them.
thoughts on the p38 is the same as my thoughts on trying to save neurons
from dying. If the primary driver of the disease is synapse loss as our
data strongly indicate, it makes the most sense to focus on blocking the
synapse loss as all the other stuff (dendritic atrophy, neuron loss, and
axonopathy) is secondary.
- If DPP=Diastolic
-IOP>50, then you are normal and should not progress. No increased risk.
Doesn't work for me though. I'm 138/79 and IOP of 16.
If your DPP>50,
you should not be progressing. If you are, you should look for the cause.
However, if DPP <50 and you are seeing changes to your OCT, then
lowering your pressure should help.
changing drops can be the difference between fast progression and no
- Ganglion Cell Complex (GCC) is the collective term for the three retinal
layers associated with ganglion cells: RNFL, ganglion cell layer and inner
plexiform layer. GCC thought to be affected in early glaucoma. Optovue OCT
has a report that measures this.
- Bosentan can protect against glaucoma damage. See
http://www.ncbi.nlm.nih.gov/pubmed/18719081. These receptors are highly
expressed by astrocytes and trigger reactive astrocytosis which is a gene
expression change. We've found that reactive astrocytes start to secrete
many complement proteins so I suspect that blocking these receptors is
accomplishing much the same thing as complement cascade inhibition. See
clustering identifies complement and endothelin induction as early events in
a mouse model of glaucoma" which says, "Similarly, inhibition of the
endothelin system with bosentan, an endothelin receptor antagonist, was
strongly protective against glaucomatous damage." What's cool is Bosentan is
an FDA approved drug now on the market. However, Ben Barres points out, "Most
drugs don't get across the blood brain barrier or into retina. This one
probably doesnt. The side effects of blocking endothelin receptors in the
eye and brain are not clear to me. I worry they could be substantial."
Calkins wrote, "Hey! Yes, this could be dangerous in glaucoma, since
bosentan is primarily in clinical trials right now for things like pulmonary
hypertension, heart disease, kidney failure etc -- organs with lots of
endothelial cells. The problem with such drugs is not the
blood-brain/blood-retina barrier, but that they can "go systemic" through
the conjunctiva of the eye. That's why the first generation of IOP-lowering
drugs (b blockers) often caused cardiac infarction! "
- If you
are taking eye drops and they aren't lowering your IOP, why are you taking
- According to David Calkins,
Brimonidine is supposed to have a neuroprotective effect so even if the
drops don't lower your IOP, they might be having positive impact.
Barres writes: I do think that imaging active complement activation
at synapses would be an incredible way to image the degree of active
glaucomatous degeneration, particularly as it could be imaged long before
axons and neurons degenerated.
- In high
pressure glaucoma, loss is steady, whereas in normal tension, loss is
episodic and you can go years between losses. That suggests that things like
lowered blood pressure might cause that (I notice my blood pressure is all
over the place...see below).
DT-MRI and fMRI analysis often involves remapping 3D
voxels onto a "standard brain"--I would think mapping one patient's scan
onto their prior scan would be fairly trivial, even with angle change.
--even with gross remapping based on blood vessels
and ignoring angle/tilt, because glaucoma progression is regional, the
calculus for change should be able to filter to include only regional
--biology may be limiting, I don't think we know if
there is biological multi-micron change in retinal tissue over short or long
periods, for example with fluid shifts. This may need to be studied or
validated at least.
--we also don't know in humans (let alone the
variation among humans) the time course between axon dysfunction, axon
injury in the optic nerve, and cell body loss in the retina. If the axons go
first, which is suggested in humans and supported in animal models, I think
axons should continue to receive some attention, both for measuring disease
and promoting survival/regeneration. (Also axon regeneration is the major
issue impeding whole eye transplant, which Larry Benowitz and Jeffrey
Goldman are trying to assemble a consortium now to address directly.)
CPAP raises IOP....not sure by how much. Proven in
non-glaucoma patients. Nobody has done a study for glaucoma patients.
Sleep apnea in glaucoma patients will actually lower
IOP at night to match IOP of patients without glacoma.
Raises IOP: smoking, caffeine, supine position (by
about 4mm plus or minus 2mm), swimming (because your head is out of the water and your body
isn't), sleeping on that side will raise IOP on that side
Lowers IOP: exercise (for several hours), revasterol, marijuana (reportedly)
Current best measure of progression is RNFL thickness.
IOP actually fluctuates by about 1mm in sync with
your heart beats.
Nothing beats the reichert 7CR for true IOP EXCEPT a
direct measurement but that is against FDA rules. If you run the Reichert on
a calibration eye, it will read exactly the same (within .1mmHg) every time.
The only drawback is must be used in sitting position.
Reichert pneumatonometer is what they use at the sleep lab at UCSD
because they need to measure you in the supine and sitting position.
Pneumatonomter uses the average of IOP of 2-3 sec time period.
Pneumatonomter uses the average of IOP of 2-3 sec time period, which should
include 2-3 cyclic changes of IOP (along with the cardiovascular cycles).
Cardiovascular cycle has a minimal effect on the pneumatonometer readings,
but the breath has its effect.
In the Topcon DRI OCT, DRI stands for "deep range
imaging". It is a spectral domain OCT but has a longer wavelength for deeper
penetration. The 200 file is the one with the smaller squares - it is a
12x9mm scan (200 micron x 60 by 200 micron x 45). The 1000 file has the scan
divided into 1000micron squares. The excel csv output file goes across
first, then up and down.
The best way to adjust for alignment is to use the
reference called the fovea-Bruch's membrane opening (BMO) axis. This will be
available soon on the Spectralis.
What happens to your diurnal IOP after surgery?
Nobody knows because they couldn't run a study because someone objected
saying the data would be useless.
Does OPP matter? Makes sense, but hard to know. No
Drops. wait 5 to 10 minutes after you open your eyes
between drops. Keep eyes closed and don't move eyes. You only need to pinch
if you want to avoid systemic absorbtion (e.g., Brimonidine).
Spectralis OCT is cool. Does a B-scan, then waits
for your eye to be in position before it does the next B scan. This is the
eye tracking technology. So it takes longer, but the images are sharper.
if you want to line up your 2D RNFL heatmaps, you
can use Gimp and use the transparency
Spectralis lacks 2D heatmap images. The topcon DRI
can dump the superpixel data to a .csv file. That is cool. But you can't
line up the data for similar scans on the same eye.
Dr. John Liu discovered that IOP might be way high
at night because saw this in animals. So he had the idea to try in humans.
Different drugs have dramatically different diurnal
curves. Some drug categories last for days, other drug types last for hours.
See notes below. Also, uniformly drugs are only 50% effective at night and
many drug types have NO effect at night.
Night (especially early morning) is likely where the
most damage occurs. You are laying down (increase of 5mm) and you IOP is
also elevated. I am 16 during the day, but 29 at 5:30am lying down!
In 50% of the people, one eye progresses first
before the other eye goes.
Once you have damage, your rate of progression
Trabectome surgery can last for months or years. Be
sure you are operated on by someone with >100 surgeries under their belt
because by then they have refined their technique.
There is risk in any eye surgery. With
trabeculectomy, there a lifetime risk of infection.
I think VERY few doctors actually know the shape of
the effectiveness curves of the drugs that they are prescribing. If they
did, they would be less likely to have prescribed Combigan to anyone.
IOP is the same whether you are exhaling or
inhaling. Breathe normally when
they take your IOP measurements. Holding breath does not necessarily make
IOP go up on GAT. "Valsalva maneuvers" will. Patient position can play a
role. With GAT, you tend to be more hunched over.
I wonder if it might be better to note the full IOP range
at any given point in time rather than trying to compute an average. To
compute the average should you take all 4 readings? or average the middle
two? or average the two extremes?
David Calkins says p38 inhibitor basically makes it
harder for cells to die when under pressure. But if cells are under too much
pressure, the p38 won't save them. So the thought is that glaucoma makes
cells more susceptible to pressure and the p38 inhibitor reverses that.
No way yet to determine if Trabectome would be
effective before the surgery is done. We have been using anterior segment
OCT to try to figure out in an individual patient where the site of
resistance in the outflow pathway is located.
Doctors use GAT instead of Reichert for two reasons:
compatibility and insurance re-imbursement code.
the 200x200 on the Cirrus report means it's 200 B
scans (line scans), each with 200 A scans. It covers a 6mm2 area.
Triggerfish results proved that IOP really rises at
night, just like the measurements confirmed.
Sleep apnea can make a glaucoma person and look like
a normal person. When you add CPAP, pressures look like a glaucoma patient.
So adding CPAP in general will raise your IOP.
when taking BP and IOP readings, maintain that state
(sitting up or lying down) for 5 minutes to allow things to stabilize
BP readings should be within 5mmHg of each other,
e.g., a good automated tester will be consistent to within 5mm on each
All eyedrops can be safely stored in the
refrigerator regardless of what they say on the label. Just don't put in
Glaucoma patients have lower BP at night but same BP
during the daytime vs. normals.
FDA limits are 5 minutes per day per eye for laser
scans (like OCT).
Uveoscleral outflow drops to nearly zero at night
(reported by Dr. Sit at 2011 ARVO). That could explain why some medications
work better during the day than at night.
You want to minimize the IOP fluctuation. Mine is
18mmHg. Red flag at 4. See
question of IOP which says:
Dr. Varma calculates the difference between the highest IOP reading and
the lowest IOP reading (taken during office visits at any time of day). He
considers any variation higher than 4 mmHg—and, especially, higher than 6
mmHg—to be a red flag.
- The more advanced the glaucoma, the more narrow the range of
variation/fluctuation should be. "Long-acting drugs are better in
controlling fluctuation, such as all prostaglandins and Cosopt," Dr. Asrani
says. "The range with these eye drops is within the range of a normal eye
fluctuation." He notes that a combination of eye drops also could be used to
attempt to control the fluctuations. Dr. Stewart agrees. "Prostaglandins
absolutely are the best class that we know about for fluctuations based on
Professor Konstas's and my findings. We found the level of fluctuation to be
the best with Travatan [3.2 mmHg], and then Lumigan [3.5 mmHg]. We had the
most experience with Xalatan [range 3.8 to 4.4 mmHg]," he says. .... Peak
IOP still most often occurs during the nocturnal period. See
- The diurnal curves are quite different between individuals, but
consistent by person (across several tests). Some people have peaks first
thing in the morning like I do (which I think is the most common time to
peak), and others have peaks at 2pm in the afternoon, etc.
Why they can't seem to measure the same pressure twice in a row on a Reichert
or Goldmann tonometer (or any other tonometer):
Screen capture of approximately six seconds of the continuous IOP and ECG
signal from an awake, unrestrained nonhuman primate implanted with Dr.
Downs’ IOP telemetry sensor. Note that the high-frequency fluctuations in
IOP are due to saccades (eye movement) and blinks. But even without the blinks, you can see
that the trough IOP pressure can vary from 8 to 14 over a 3 second period!!!
This is why they always get different readings when they measure your IOP,
no matter how accurate the tonometer. This is from
question of IOP.
This also explains why a Reichert 7CR measured me at 14 and 10, just
seconds apart. I thought the machine was bad. But if you put a Reichert on a
non-human "test eye," the readings are accurate to within .1mmHg.
There is also a waveform score that tells you how confident the machine
was that it got a valid reading. Generally scores over 6 will give very
reliable measurements. Most all self-tonometers lack this important feature
(and it's really important since bad technique can give you bad measurements
for most tonometers).
The Reichert air puff interval is 20 msec, and the inward/outward
measurement of the 3mm diameter circle of the cornea is within 10 msec.
the Reichert gives essentially an "instantaneous" measurement. So you
can't take just a single snapshot on the Reichert because you might get
unlucky and catch an IOP spike due to blinking, movement, fluctuations
from the ocular pulse, and real variations in the trough IOP level that are constantly happening even over a time
interval as short as a few seconds.
So looking at the graph above, that
explains the wide range of IOP readings . Also, the Reichert is the only
non-invasive technique I am aware of that can properly adjust for cornea
properties (of which thickness is just one property) to tell you your true IOP. This is important because you cannot use cornea
thickness to "correct" a Goldmann measurement because even the direction of
the change depends on the dynamics of your cornea. So a thicker cornea might
cause your Goldmann reading to be higher or lower. The only way to know is
to use the Reichert on your eye and look at the IOPcc measurement. In
general, Goldmann is really no longer state of the art, but physicians'
habits are really hard to break. Note: you could argue that the "true" IOP
doesn't matter since your cornea tends not to change so the Goldmann IOP is
just fine as a relative measure of IOP.
Simplest IOP number when using a Reichert is to use the 3 puff average
score. It looks at the "score" (not the IOP value) to determine weighting of
If you are using a Reichert, because the peaks are really short and
can vary a lot, it seems to me it would be much better to measure the lowest IOP value taken over several measurements (as long as the "score" is high so
it is a good measurement), rather than just a single or mean value. This is
because a trough measurement is much easier to take (and more meaningful)
since it is sitting in the trough for most of the time of a measurement.
Why complement cascade is a very interesting pathway
However, in the mouse model of glaucoma, which very
very closely if not identically models human glaucoma (which is quite nice
because many animal models for other diseases do not mimic the human
disease), one can watch progress loss of optic nerve axons over the 1 to 2
year course of the disease. In this model, the loss of optic nerve axons
very closely tracks the death of retinal ganglion cells.
In case of
interest, in this model, death of retinal ganglion cells starts to happen
around 10 months of age however we have shown that complement activation at
their synapses has already begun by 2 months of age and that massive loss of
synapses is occurring already at 3 to 4 months of age (we have so far only
looked at the synapse onto the retinal ganglion cells within the retina, but
we presume the same thing is happening at the retinal ganglion cell synapses
within the brain). This suggests that axons are ultimately lost because the
synapses have degenerated. In fact, we showed in this mouse model by
measuring how much optic nerve axon loss had occurred that by 11 months of
age, the majority of control mice (with a normal complement system), had
either moderate or severe glaucoma (optic nerve axon loss) whereas in
complement knockout mice (that lacked the complement protein C1q), almost
none had any evidence of glaucoma at all (we published this a couple of
years ago). Blocking the complement system is profoundly neuroprotective
for glaucoma. I hope that Calkins target works as well, but so far no
other manipulation has come close to having such a profound effect, even the
Wlds mutation which is a powerful promoter of axon survival
Advice I've received
first in regard to your eye problem:I
don’t think there is much in non-IOP (intraocular pressure) clinical trials
yet, but there are a number of compounds moving closer. I have participated
in a few trial design advisory boards. Bob Weinreb (my chair) is very
well-connected and will be able to keep Steve in the loop too. What the
field really needs is a group to fund bringing candidates from the lab to
the clinic. As for the ischemia from hyperviscosity, as you know that’s a
principle hypothesis for etiology. There are some papers from China on
hyperviscosity association with glaucoma but I don’t think that’s gone very
far in research.
regard to Calkins drug target, in regard to your visual fields:
That kind of thing just needs to be tried. But looking at his visual fields
I wouldn’t recommend he be the first guinea pig on any of these. Relatively
speaking he is in decent shape, although I appreciate that if his functional
vision is greatly impacted he might be motivated to try things...
Sleep study 12/8/13
The operated on eye never got above 25, where as the
unoperated eye hit 29. So great news there.
The biggest delta between the eyes was sleeping on right
side. Left eye was 21, right eye was 26
Sp02 no diff with and without cpap, HOWEVER, spo2 got down
to 95 but don’t know for how long. John would have to chart it. That was the big
surprise, but in general
CPAP: no diff. you can’t really argue it raised pressures.
We did some tests at the start and there was no difference when I was under
pressure or not on these tests, nor did the overall sleep study give pressures
that we statistically significant lower. It clearly didn’t make things worse. If
anything it made it better.
Sleep study 8/17/13
sleep data. Note: They wake you up to take the measurements. For IOP,
they use a
Reichert pneumatonometer since it can measure while you are in the
Pressure in OS varied from 12.5 at 6:30pm (sitting) to 30.5 at 6:30am supine.
So that is a huge variation.
Diurnal Variation in IOP found that Risk of disease progression within 5
years was six times higher for patients who had a diurnal IOP range of 5.4 mm Hg
than for those with a diurnal IOP range of 3.1 mm Hg.
Comments from a doctor:
Independently of any other consideration, he should most definitely do a
much better job of controlling his systolic blood pressure. It’s
anomalously high for his age, especially when he’s supine-&-asleep! He
should never tolerate a systolic pressure in excess of 120 mm-Hg under any
conditions other than vigorous exercise, using an angiotensin receptor
blocker (I recommend the modern type II flavor, e.g., valsartan-taken-daily)
for long-term control, and a fast-acting peripheral vascular
resistance-reducer, e.g., nicardipine-as-needed, for suppressing
I predict a dramatic improvement in nocturnal regulation of intraocular
pressure if he steadfastly controls his systolic pressure. [He’ll also
do his cerebral and renal capillary beds a huge favor by doing so – they age
linearly more rapidly as the mean pulse pressure climbs above a threshold of
~95 mm-Hg and, while his generally-good diastolic BP ‘helps’, it can’t save
these crucial tissues from the ravages of his excessive systolic BP.] His
intraocular pressure appears to be exceptionally sensitive to local blood
pressure, as gauged by supine-vs.-sitting nocturnal measurements.
He may also benefit from seeing a cardiologist re getting active medical
management of his nocturnal pulse rate, which seems quite high for his age
and nominal health. Reducing it below ~80 BPM likely will help control
nocturnal IOP to some degree, though less so than improved systolic BP
However, the optimal level of BP at night for glaucoma is not known.
Lowering BP will have an imperceptible effect on IOP.
Trabectome surgery 8/26/13
Had trabectome surgery in my left eye. Next morning, IOP was 9 (at 8:30am). 1
week later it is 16 (at 2pm).
Medications: Prednisolone acetate is 1/hr then once every 2 hours starting on
Friday. SHAKE it before use. Pilocarpine and zymaxid are to be used 4X/day
(wake, noon, dinner, before bed).
Other: Protect eye with glasses during the day. At nigh, need to sleep with
plastic eye protection patch for 2 weeks after surgery. Do NOT get the eye wet
(lots of bad stuff in water).. Pinching is a good idea. Use dry tissue to clean debris around the
eye. Minimize lifting and straining. Keep head above your heart at all times.
sleep so that left eye is elevated. Next appt is 1 week out. No golf, situps,
etc. Minimize nose blow, valsalva, etc. No sleep study for 3 months after eye
operation. the feeling that there is something in my eye will go away in 2 days
(it did). Because
there is a hole in my eye that hasn't fully healed, it may NOT be bacteria
resistant so that's why need to keep bacteria from the eye which is why water is
a no no (it has tons of bacteria). Vision will get
progressively better. By friday, left eye was slightly less sharp than right
Safest way to clean all the junk around the eye and on eyelid in the first
two weeks after surgery: get sterile qtips saturated with sterile saline.
Side effects of pilocarpine: head and brow ache: can take tylenol.
It will also make your pupil small.
Not designed for self tonometry, but they've sold over 200 that were
purchased by glaucoma patients for use at home. You have to reach around to hit the button.
It won't show you each result indpendently. If take three measures, it will
either average them or take the highest, whereas you really want the lowest so
need to clear it between each measurement. So easiest to set up a mirror so you
can see what is going on.
Low confidence score= you are moving your eye too much or
not straight up and down. But anything above 6 is going to be pretty accurate.
If you keep you eye steady, you can get up to 9.5 score.
If you do single measurements, the Reichert will remember a
maximum of 3 measurements with waveform scores that are within 1 unit of each
other. So the new measurement goes in only if has a higher "score" than the 3
that are there. Exception: if you hit the 3 puffs button, it clears all 3 scores
when you hit the button.
So if you are using the single button alone, or after you
hit the 3 puff button (and before you hit the next 3 puff button), it works like
1) Take measurements
Maximum number of measurements in memory is 3
2) The measurement with highest Waveform Score (WS) is identified internally
by the software
3) All measurement(s) with a WS within 1.0 of Maximum WS, will be averaged
to be displayed as IOPg, IOPcc & WS
4) After three measurements have been taken, a new measurement will replace
the lowest waveform score measurement and steps 2 & 3 are repeated.
Super low IOP 1/14/2014
Measured a new low at 11pm last night: 7.5 OS 9.3
My day was unusual for many reasons: late lunch, late dinner, ate at places I
rarely eat at.
8:30am: Breakfast at Buck's restaurant: a filoli omelette (healthy version)
with salsa, english muffin, and OJ
I starved at a meeting and finally went for a LATE Lunch at 3pm a new Chinese
place in the mall I've never eaten at (it used to be Thai Orchid). I ordered the
miso soup, and the tomato beef lunch special.
Dinner when I got home at 10pm was chicken and potatoes with Jack Daniels
Master BBQ sauce on the chicken and fresh squeezed OJ to drink.
The only medication I took all day was Alphagan-P at 4pm (from a previously
unopened bottle) and Lumigan the night before. So it wasn't the drugs.
Without the home Reichert, I never would have discovered this very
I repeated the measurement just to be sure and got 8.0 and 9.9. Stunning.
Just to be sure the machine wasn't broken, I then measured at 5:30am the next
morning, immediately after hopping out of bed: 18.2 and 15.6
It appears that Something VERY interesting just happened.
IOP Test results
IOP before I started having problems with the field loss
2001: 15, 15
2004: 15, 17
2005: 14, 14
2006: 15, 13
2007: 14, 14
4/1/08: 13, 16
5/20/09: 13, 14
8/18/10: 14, 15
My visual fields and IOP measurements
glaucoma test data (everything I have)
||Probably developed sleep apnea around this time, but never knew it.
Snoring has gotten worse over time.
||Diagnosed with Waldenstrom's Macroglobulinemia.
Kirsch Waldenstrom's Macroglobulinemia Diary
is diary of drugs used and blood tests.
||Surgery to remove appendix in Boston, MA. It was caught early, doing
a routine medical exam. I was lucky.
||High IgM event caused by Rituxan infusion to treat my Waldenstrom's.
||Visual fields test at my annual eye exam shows vision loss in left
eye. Doc thinks glaucoma so refers me to Tayeri.
||Saw Tayeri for consultation because my regular eye doctor (Gary
Stocker) noticed abnormality in visual fields which was likely caused by
the high IgM event.
||Started enzastaurin trial for my WM
||Started LBH trial in Boston. Moved to Denver 10/26/10.
||Surgery to remove gall bladder due to gallstones. I am now a shadow
of my former self...no appendix, no gallbladder. Will my wife still love
Have had sleep apnea for a while, possibly a decade or more. Started
using CPAP religiously due to the Respironics System One which is a
fantastic improvement to the CPAP I used to have. So since CPAP
added very late in the game, it is likely not the cause of my glaucoma.
||Tayeri said my vision progressing too fast and I need surgery to get
the pressures under 10. Saw Iwach. Changed medications to Zioptan,
||Iwach did SLT surgery on my left eye.
||Pressure check at Iwach two-weeks post-surgery 10, 12 (left, right)
||Saw Weinreb. Pressures back at 14 to 16 on Iwach's drugs. Weinreb
told me to switch to his set of drugs which I did same day.
||Shared my data with Marty Wax. He thinks the WM is the 800 lb
Gorilla in my case.
||Sleep study. Pressure in OS varied from 12.5 at 6:30pm (sitting) to
30.5 at 6:30am supine. See
sleep data. My systolic pressure is pretty high at night (150 which
is well above the 120 it should be) and my heartrate is high as well
(should be below 80 bpm)
||Tabectome surgery in OS. IOP in OS is 9 the next morning. Will it
last? We shall see.
Visual fields loss in left eye over time
||Visual Fields (OD)
||Visual Fields (OS)
||Medications prior to this measurement
||Xalatan left eye at night
||No medications for 6 months before this test
||No medications for approximately 1.5 years prior
||In the year prior, [Brimonidine, Combigan, none] given during this
period (except for a 2 month period on Xalatan). These drugs have no
effect at night (execept Xalatan). So nighttime pressures for 1 year
were not treated except for a 2 month period.
||Combigan (which has no effect at night)
||different drugs (some of which have effect at night)
6/10/13 Cirrus OCT RNFL
||RNFL thickness (OD)
||RNFL thickness (OS)
||Xalatan OS qhs
||Xalatan OU QHS
||Brimonidine OU bid
Zioptan (before bed)
Timolol Maleate (morning)
Latanoprost .005% (green top): at bedtime
Alphagan-P .1% (purple top): morning, afternoon
Azopt 1% (orange top): 3X/day
Zioptan (Tafluprost ophthalmic solution)
|Dosed once a day, typically at night because that way
you don't see the red eye effect.
These drugs have
peak effect at 8 to 12 hours after instillation so timed to have max
effect when your IOP peaks. They last a long time (a very flat efficacy
curve and it still has impact on day 2), and they work at night.
1/8 patients respond much
better to Lumigan, but side effects are 2 to 3 times more likely with
Prostaglandin analog trio equally effective in lowering IOP) which
is why they lowered the formulation from .03 to .01%.
patients may respond differently to drugs within this class so you
really should try and see what works best for you. For example, Lumigan
in one patient lowered pressure 7mm more than Travatan plus Alphagan! In
some patients, Lumigan is very good at controlling morning peaks which can be
critically important (e.g., in people like me). So this is why it is
important to try different drugs to see how they work for you.
The expected IOP drop from baseline averages about 30% with once-daily
dosing. Reduction in peak IOP: bimatoprost (33%), latanoprost (31%),
travoprost (31%) and timolol (27%).
Reduction in trough IOP: travoprost (31%), bimatoprost (28%),
latanoprost (28%) and timolol (26%).
Travoprost caused significantly more ocular hyperemia and eyelash
changes than timolol or latanoprost and was equivalent to bimatoprost
for these events
Bimatoprost may decrease IOP slightly more than latanoprost and
travoprost, however the clinical significance of this difference is not
Side effects such as hyperemia, ocular pruritus, and eyelash
growth are reported to occur more often with bimatoprost
Doctors often prescribe prostaglandins to treat
open-angle glaucoma. These eyedrops increase the outflow of the fluid in
your eye (aqueous humor) and reduce pressure in your eye. Examples
include latanoprost (Xalatan) and bimatoprost (Lumigan). Possible side
effects include mild reddening and stinging of the eyes and darkening of
the iris, changes in the pigment of the eyelid skin and blurred vision.
Because these medications are fairly new to the market, complete, long
term side effects are yet to be documented, and in fact, there is a
newer side effect known as
Ophthalmic Prostaglandins Review for detailed comparison. Also
New drug Travatan shows excellent IOP lowering results in clinical
|Alphagan-P (Brimonidine tartrate)
Unlike Prostaglandins which have a pretty flat response curve (long
half life but 50% effective at night), Brimonidine peaks in 1 to 4 hours
with a half life of 3 hours and has minimal impact at night.
These drugs, like beta
blockers, do NOT work at NIGHT so it is stupid to take them 3X/day like
on the label. This is why smart doctors tell you to take it in the
morning, then 8 hours later. Max two doses/day.
These medications reduce the production of aqueous humor
and increase outflow of the fluid in your eye. Examples include
apraclonidine (Iopidine) and brimonidine (Alphagan). Possible
side effects include irregular heart rate, high blood pressure, fatigue,
red, itchy or swollen eyes, and dry mouth.
Pinch your nose when taking to reduce
potential for CNS systemic effects.
Note that brimonidine is
said to have neuro-protective effects as well
|Azopt (Brinzolamide ophthalmic suspension)
||This has a relatively short effectiveness profile,
peaking at around 4-6 hours. They work at night as well as during the
daytime. Because of the short effectiveness profile, it is prescribed
for use 3 times a day.
It may not lower IOP in some patients.
Experts say that "the best options [for lowering and stabilizing IOP]
would be the prostaglandin analogs and carbonic anhydrase inhibitors"
"The Question of IOP" in June 2011 issue of AAO EyeNet).
These medications may reduce
the production of fluid in your eye. Examples include dorzolamide (Trusopt)
and brinzolamide (Azopt). Possible side effects include frequent
urination and a tingling sensation in the fingers and toes.
effects in drop form includes stinging, burning, eye discomfort.
In pill form, there can be paresthesias, upset stomach, memory
problems, depression and frequent urination.
|beta blocker aka beta adrenergic blocker
agonists, these drugs do not work at night.
Timolol can lower your blood pressure
which (if you believe the OPP impacts glaucoma progression) is a really
bad thing if you have glaucoma.
Betaxolol lowers IOP without affective blood pressure much.
One patient consistently dropped 22 points (systolic) and 15 points
(diastolic) on Timolol. That can have a huge impact on glaucoma
progression. When that patient switched to Lumigan, he went from a rapid
progression to no progression. This was
likely due to two important factors: Lumigan provides 24 hour IOP
and Lumigan does not lower your blood pressure.
On the bright side, Timolol can lower
your IOP during the daytime. One person went from 30 to 16 in just 24
Ask your physician why he is doing
this if this is one of your medications and if you still do it, monitor
your blood pressure before and after.
||Combigan (brimonidine and timolol) when prescribed as a
mono therapy for glaucoma is puzzling to me. There is good evidence that
most of the damage is done at night and both of these drugs in combigan
do NOT work at night.
The drug got FDA approval because it works in the day
time, but the FDA hasn't figured out yet that IOP is highest at night.
There is no point in taking this drug at night because there is no
You should not assume that just because a drug got FDA approval, it
is a good drug to prescribe. One world expert in glaucoma I consulted
pointed out that there are a lot of these glaucoma combination drugs
that makes absolutely no sense and he never prescribes them.
For most patients (whose IOP is highest at night), taking this drug
may be worse than taking a placebo because not only is it ineffective at
night, but the timolol can lower your blood pressure which is a risk
factor for progression.
I highly urge anyone who has been prescribed this drug as a
monotherapy to ask their doctor for peer reviewed papers showing this
combination works at night because just the opposite is true (there are
papers showing it doesn't). I was prescribed this drug as a monotherapy
and some of the worst progression I had was when I was on this drug.
||Azopt + brimonidine. This isn't nearly as bad a combo as
combigan and saves time, but the brimonidine on the third daily dose is
pretty much wasted (since tiny impact at night) so you end up overdosing for
Also, the .2% brimonidine in Simbrinza has higher allergy rate and
more redness than the standard 0.1%. Moreover the 0.2% does not offer
any advantage in IOP-lowering vs. .1%.
So like Combigan, this is a drug that you really have to wonder why
physicians prescribe it (the only reason I can think of would be for
patients who have a compliance problem).
If you still end up using it, do it for Morning and afternoon only. But for just before bed, you should do a Prostaglandin and Azopt.
How to apply eye drops
diastolic OPP (DOPP)=diastolic
BP-IOP. Under 50 is risky.
reliability of candidate tonometers for measuring intraocular pressure Shows
that non-contact (air puff) tonometers agree within 0.28mmHg with GAT. This is a
surprise to most physicians.
OCT measurement consistency: this is the key. It indicates you can get very
stable numbers if the system is set up right. This is absolutely required in
order to see the small changes that happen each day for someone rapidly
progressing. It also suggests that if a reference image is made part of the
system, you should be able to determine before the scan if the image is lined up
and in focus. Done right, you can get <1um standard deviation between scans. So
there is still a question about the reproducibility of dirunal data...should you
average over the entire day? Should you take all samples at a certain time of
Distribution of Ocular Perfusion Pressure and Its Relationship with Open-Angle
Glaucoma: The Singapore Malay Eye Study. Mean ocular perfusion
pressure (MOPP) = ⅔(mean arterial pressure − IOP), where mean arterial pressure
(MAP) = DBP + ⅓(SBP − DBP), systolic perfusion pressure (SPP) = SBP − IOP, and
diastolic perfusion pressure (DPP) = DBP − IOP. Low DBP, low MOPP, and low DPP
are independent risk factors for OAG.
Is Normal Tension Glaucoma a
Clinically Distinct Entity? Talks about CSF and blood pressure
Triggerfish shows 24 hour IOP fluctuations
Reading OCT reports
Comparison of OCT devices
disk images and explanation
OPP article “In our study, we found that both ends of the blood pressure
spectrum are damaging to the optic nerve.”
WALDENSTROM AND THE
EYE by Dr. Maureen Hanley
Normal-pressure glaucoma may be autoimmune
neuropathy. Scerra, Chet // Ophthalmology Times;6/1/2003, Vol. 28
Issue 11, p16
Examines the relationship between the immune system and
glaucoma. Evidence that normal pressure glaucoma (NPG) may represent an
autoimmune neuropathy; Role played by the immune system in neuronal death among
NPG patients; Hypothesis on the association of neurodegenerative processes in
The expected IOP drop from baseline averages about 30% with once-daily dosing.
Evening dosing is preferred as the onset of IOP lowering activity for
prostaglandin analogues is slow with peak effect at 8 to 12 hours after
instillation. Compare this with the two-hour peak efficacy of the beta-blockers,
The recommended dosing regimen for Latanoprost, Travoprost and Bimatoprost is
once daily topical application preferably in the evening to reduce the early
morning dirunal spike. (p. 16)
IOP should be rechecked
at the drug's peak and trough times to see if the target IOP has been reached
and is maintained throughout the day.
beginning, OCT represented a trend-setting collaboration between engineering and
medicine that dramatically improved patient care. The first publication on this
innovative imaging technology appeared in Science in November 1991,1
following 10 years of work by Carmen A. Puliafito, MD, MBA, at Harvard Medical
School, and James G. Fujimoto, professor of electrical engineering at the
Massachusetts Institute of Technology. The goal of their work was to use short
pulse lasers to measure ocular structures.
inferotemporal (7 o’clock) sector was the most frequent location that showed
progression, suggesting that this location is not only important in
discriminating glaucomatous from healthy eyes10,11,26
but it should also play an important role in detecting glaucomatous progression.
For the global RNFL thickness, mean rate of change was −0.72 μm/year for
progressors and 0.14 μm/year for non-progressors. The rates of change were
widely variable among the eyes.
cell complex is composed of the macular nerve fiber layer, ganglion cell layer,
and inner plexiform layer. Assessment of these layers has been shown to have an
improved ability to detect glaucoma compared with using full retinal thickness.
Ganglion cell complex diagnostic accuracy for detecting glaucoma has been shown
to be similar to that of peripapillary RNFL thickness,48–52
making it potentially valuable for monitoring glaucoma progression.
New Cirrus OCT
6.0 features Ganglion
Cell OU Analysis: Macular Cube 512x128.
Diurnal Variation in IOP
Diurnal variation of intraocular pressure in suspected glaucoma patients and
about use of medications like cortisones (post surgery), drugs that lower blood
pressure (like Timolol), and drugs that dilate the pupil.
http://willsglaucoma.org You can search physician/patient q&a
conversations. Very helpful site.
study re: how fast retinal thickness (independent of glaucoma)
decreases each year with age
Retinal nerve fibre
layer and visual function loss in glaucoma: the tipping point
intersession, and interexaminer variabilities of retinal nerve fiber layer
measurements with spectral-domain OCT
Steve Kirsch home page
Comments from readers
Thanks, Rich. This man must have a lot of free time. He
did an excellent job of reviewing the topic. Some of the auto-immune and other
possible alternate therapies are under investigation and not yet accepted as
therapy. He did a nice summary and I agree mainly on three points.
a) most ophths do not do nocturnal BP (I have for many
b) almost none of us do noctural intraocular
pressures.The instruments are too expensive for patients and are hard to loan
out. Patients get confused and breakage is a problem. I'll bet going to Bob
Weinreb's sleep lab cost a fortune and probably isn't covered.
c) I agree that most ophths don't appreciate the 24h
effectiveness of these drugs.
A nice piece by a smart man.