T H E O P H T H A L M I C A S C | A U G U S T 2 0 1 6
OASC | CATARACT SURGERY
▲By Desiree Ifft, Contributing Editor
Experts discuss new options for drug delivery in the ASC
To Drop or Not to Drop?
CATARACT SURGERY:
6
Cataract surgery is one of the most
frequently performed medical proce-
dures in the United States, and with
that comes great interest in anything
that may further reduce complications
or improve outcomes. This includes potential modi-
fications of the perioperative medication protocol.
Currently, surgeons can consider making several
changes: switching from topical endophthalmitis
prophylaxis to intracameral; adding or removing
a nonsteroidal anti-inflammatory (NSAID) drop;
or adopting the newest drug formulations and
delivery methods designed to reduce or
eliminate the need for patients to use
pre- and/or post-op drops.
Endophthalmitis Prophylaxis
In 2007, the European Society of
Cataract and Refractive Surgeons
(ESCRS) published the results of a
prospective multicenter randomized
clinical trial designed to evaluate anti-
biotic prophylaxis for cataract surgery.1
The key finding from the study was a
fivefold reduction in the endophthalmi-
tis rate for patients who were randomized
to receive intracameral antibiotics at the end
of the procedure compared with patients who
didn’t receive intracameral antibiotics. Patients
in the four treatment arms received either 1) no topi-
cal or intracameral antibiotics; 2) intracameral cefuroxime;
3) topical levofloxacin only; or 4) topical levofloxacin and
intracameral cefuroxime. The rates of endophthalmitis (con-
firmed by culture) were 0.226% and 0.173% in the groups
that did not receive intracameral cefurox-
ime (1 and 3), and 0.049% and 0.025% in
the groups that received intracameral pro-
phylaxis (2 and 4).
Shortly thereafter, the American
Society of Cataract and Refractive Surgery
(ASCRS) surveyed its membership to
assess whether the ESCRS study had an
impact on antibiotic prophylaxis prac-
tice patterns for cataract surgery, which,
for many surgeons in the United States,
had been prophylaxis with topical fluoroquinolones. While
16% of respondents reported they had been injecting intra-
cameral antibiotics before the ESCRS study, and 7% of
respondents reported they had recently started or planned to
start injecting intracameral antibiotics, 77% did not plan to
change their protocols.2
However, since that time, a significant number of studies,
most retrospective/observational, have shown intracameral
antibiotics injected at the end of cataract surgery to be effi-
cacious in preventing post-op endophthalmitis, and in some
studies, intracameral antibiotics were shown to be superior
to drops. By the time ASCRS re-surveyed its membership in
2014, the body of evidence had apparently prompted more
significant change. According to the 2014 study results, com-
pared with 2007, the percentage of surgeons injecting intra-
cameral antibiotics increased from 14% to 36%.3 (Sixty-five
percent of the survey respondents were from the United
States; 9% were from Europe.) The percentage of surgeons
using any type of intracameral antibiotic, including those
who were adding antibiotic to the irrigating bottle (16%)
increased from 30% in 2007 to 50% in 2014. “This is a sig-
nificant increase over the results from our 2007 survey,” says
David F. Chang, MD, clinical professor at the University of
California, San Francisco and advisory member and former
chair of the ASCRS Cataract Clinical Committee.
Still, despite additional studies in favor of intracam-
eral antibiotic injections, which have involved hundreds of
thousands of patients around the world,4-7 not everyone is
convinced. A 2016 editorial in the journal Ophthalmology
pointed to the limitations of retrospective studies, the exis-
tence of data that doesn’t support the intracameral approach
as superior, increasing drug resistance, and other factors.
The editorial went on to say that “The role of intracam-
eral antibiotics remains controversial in the United States
and in many other nations. ... The use of intracameral
antibiotics should not be considered ‘standard of care’ in the
United States, and the value of this strategy remains uncer-
tain on the basis of currently available data.”8
Dr. Chang has a different view. “Although they are mostly
retrospective studies, when taken as a whole, the published
evidence that intracameral antibiotics lower the rate of endo-
phthalmitis is overwhelming, in my opinion,” he says, adding,
“I’ve used intracameral prophylaxis for more than 15 years
with no complications.”
CATARACT SURGERY | OASC
T H E O P H T H A L M I C A S C | A U G U S T 2 0 1 6 7
“ Although they are mostly retrospective studies, when taken as a whole, the published evidence that intracameral antibiotics lower the rate of
endophthalmitis is overwhelming, in my opinion.”— David F. Chang, MD, clinical professor at the University of California,
San Francisco and advisory member and former chair
of the ASCRS Cataract Clinical Committee
T H E O P H T H A L M I C A S C | A U G U S T 2 0 1 68
OASC | CATARACT SURGERY
Francis S. Mah, MD, a cataract,
corneal, and refractive surgeon with
Scripps Health in California, believes
cataract surgery in the U.S. is in the
middle of a paradigm shift toward
intracameral and away from topi-
cal prophylaxis. Currently, his peri-
operative regimen for patients not at
increased risk of infection or cystoid
macular edema (CME) is an antibiotic
drop and an NSAID drop in the pre-
op holding area; povidone iodine 5%
(around the eyelid and a drop in the
eye); a 0.15 mL intracameral injec-
tion of compounded Dex-Moxi (dexa-
methasone 150 mcg and moxifloxacin
750 mcg, Ocular Science) at the conclu-
sion of the procedure; and an NSAID
drop, Ilevro (nepafenac ophthalmic
suspension 0.3%, Alcon), once a day
for 4 weeks; and a steroid drop, Durezol
(difluprednate ophthalmic emulsion
0.05%, Alcon), once a day for 4 weeks.
(For patients at high risk for CME,
based on peak incidence data, he adds
the NSAID drop for 3 days pre-op and
extends the post-op NSAID drop to
2 months.) In addition to the research
supporting the use of intracameral
antibiotics, Dr. Mah sees costs and
compliance as reasons to change. “The
cost of medications has become oner-
ous for patients, and their compliance
with often complicated post-op drop
regimens is questionable. Delivering
antibiotics intracamerally at the end
of surgery reduces or eliminates the
number of post-op medications
patients need to purchase and use,
which lowers their costs, and we don’t
have to worry about poor compliance
adversely affecting surgical outcomes,”
he says. The cost of the compounded
steroid/antibiotic Dr. Mah injects, $20
per patient, is absorbed by the ASC.
P. Dee Stephenson, MD, FACS, pres-
ident of the American College of Eye
Surgeons and founder of Stephenson
Eye Associates in Venice, Fla., is among
the surgeons not injecting intracam-
eral antibiotics as part of their cataract
surgeries. Focused on premium refrac-
tive cataract surgery, she prescribes
Besivance (besifloxacin ophthalmic
suspension 0.6%, Bausch + Lomb)
twice a day and Prolensa (bromf-
enac ophthalmic solution 0.07%,
Bausch + Lomb) once a day for 3 days
prior to surgery. In the pre-op hold-
ing area, she uses povidone iodine
5% (around the eyelid and a drop in
the eye). Intraoperatively, she mixes
powdered vancomycin into the BSS
bottle, and, when appropriate, utilizes
Omidria (phenylephrine and ketorolac
1% / 0.3%, Omeros). Postoperatively,
she has patients use Besivance twice a
day for 14 days, Prolensa once a day
for 6 weeks, and Lotemax (lotepred-
nol etabonate ophthalmic gel 0.5%,
Bausch + Lomb) four times a day for
2 weeks, three times a day for a week,
twice a day for a week, and once a day
for a week. The $3.14 per gram cost of
the antibiotic for the BSS is absorbed by
the ASC.
Dr. Stephenson hasn’t had a case of
endophthalmitis in the past 15 years,
but says the studies showing intra-
cameral antibiotics can lower the risk
haven’t escaped her attention. Her rea-
sons for not using intracameral anti-
biotics are largely medicolegal. “Most
surgeons in my area don’t use them,”
she says. “Drops are the local standard
of care. I’m not sure I’d be backed up
medicolegally if I were working out-
side of that and a patient developed
endophthalmitis or toxic anterior seg-
ment syndrome (TASS) related to the
off-label injection.” Fluids and medica-
tions used during surgery are among
the several suspected causes of TASS.
Dr. Stephenson also says the use of
intracameral antibiotics is more wide-
spread in Europe because surgeons
there have access to an approved for-
mulation for this purpose, Aprokam
(cefuroxime, Thea Pharmaceuticals),
which isn’t the case in the United States.
Which antibiotic is best suited for
intracameral prophylaxis is another
important question, Dr. Stephenson
continues. Several properties must be
considered, including potency, dura-
tion of action, range of bacteria types
killed or inhibited, penetration and
safety in ocular tissue, and likelihood
of causing anaphylaxis. Dr. Chang and
colleagues recently published the largest
retrospective study to date that shows
the efficacy of intracameral moxi-
floxacin in reducing the rate of endo-
phthalmitis.9 According to the results
of the 2014 ASCRS survey, among sur-
geons using intracameral antibiotics,
“ Drops are the local standard of care. I’m not sure I’d be backed up medicolegally if I were
working outside of that and a patient developed endophthalmitis or toxic anterior segment
syndrome related to the off-label injection.”— P. Dee Stephenson, MD, FACS, president of the American College of Eye Surgeons
and founder of Stephenson Eye Associates in Venice, Fla.
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T H E O P H T H A L M I C A S C | A U G U S T 2 0 1 610
OASC | CATARACT SURGERY
37% overall and 52% of American sur-
geons were using vancomycin, and 33%
overall and 31% of American surgeons
were using moxifloxacin.3
However, Dr. Chang and others
have switched from intracameral van-
comycin to moxifloxacin because of
the recently published moxifloxacin
study and the emergence of increas-
ing numbers of cases of postoperative
hemorrhagic occlusive retinal vas-
culitis (HORV).10 He’s part of a joint
ASCRS-American Society of Retina
Specialists task force that was formed
following the initial report of HORV.
“Based on approximately 30 total
cases, the association with vancomy-
cin is very convincing and is probably
due to a rare, delayed Type III hyper-
sensitivity,” he explains. “Because the
retinal vasculitis and visual loss are
delayed, many of these patients are
bilaterally blind after receiving van-
comycin in both eyes following cata-
ract surgery. I now use compounded
moxifloxacin (1 mg/0.1 mL) from
Leiter’s Compounding Pharmacy, an
FDA-registered pharmacy. The com-
pounded product has a very stable shelf
life and is less expensive than a bottle
of Vigamox (moxifloxacin hydro-
chloride ophthalmic solution 0.5%,
Alcon). California is one of 33 states
that doesn’t require a written prescrip-
tion for each patient.” Dr. Chang notes
that Vigamox isn’t manufactured with
the intent of intracameral injection and
can’t be autoclaved.
NSAIDs for Inflammation Control
Controlling postoperative pain and
inflammation and preventing CME
are important goals for an increasing
number of cataract surgeons, espe-
cially those who provide premium
procedures. In a 2014 survey of ASCRS
members, 41.2% of respondents
strongly agreed that low-to-moderate
inflammation can significantly impact
variability in visual acuity and quality
results, and 40.2% reported using both
topical NSAIDs and steroids at 1 day
post-op.11 According to Dr. Mah, the
percentage of surgeons who prescribe a
topical NSAID at some point surround-
ing cataract surgery is close to 70%.
Last year, the American Academy of
Ophthalmology (AAO) published an
Ophthalmic Technology Assessment
regarding topical NSAIDs and cataract
surgery. While the report concluded
“Cystoid macular edema after cataract
surgery has a tendency to resolve spon-
taneously” and called into question the
strength of the evidence in support of
NSAID use in routine cases,12 propo-
nents of the strategy have been unde-
terred. Regarding the AAO report,
Dr. Mah says, “The authors correctly
state that NSAID use typically has
no effect on visual outcomes after
3 months; but they also correctly state
that it does make a difference prior
to 3 months. This may mean faster
visual recovery, which is beneficial for
patients, and arguably, for example, one
of the main reasons phaco overtook
extracapsular extraction as the pre-
dominant method of cataract surgery.
Many studies have shown a reduced
incidence of CME when topical
NSAIDs are used, and although Snellen
visual acuity may not be adversely
affected, I would argue that there is an
impact on aspects of vision that haven’t
traditionally been measured, such as
contrast sensitivity.”
Dr. Mah and Dr. Stephenson main-
tain that the evidence in favor of
NSAIDs is strong and in line with their
clinical experiences. They say both
confirm for them that even patients
considered low-risk can develop CME,
which adversely affects quality of
vision; NSAIDs reduce CME rates in
both low- and high-risk patients; and
NSAIDs, either alone or in combina-
tion with steroids, can prevent CME
and control inflammation more effec-
tively than steroids alone.13-18
Dr. Mah wouldn’t be surprised if
the use of NSAIDS with cataract sur-
gery, whether it be before, during, and/
or after, continues to increase. As he
sees it, “With the high expectations
for superb vision that we’re aiming to
fulfill, we really can’t afford for our
patients to have drawbacks like inflam-
mation and CME, which we know are
largely preventable.”
Finding New Options
According to Dr. Stephenson, the use of
Omidria as an integral part of cataract
surgery, especially femtosecond laser-
assisted cataract surgery, is increasing.
“ With the high expectations for superb vision that we’re aiming to fulfill, we really can’t
afford for our patients to have drawbacks like inflammation and cystoid macular edema, which
we know are largely preventable.”— Francis S. Mah, MD, a cataract, corneal, and refractive surgeon with
Scripps Health in California
T H E O P H T H A L M I C A S C | A U G U S T 2 0 1 6 11
CATARACT SURGERY | OASC
The phenylephrine/ketorolac formu-
lation, added to the intraoperative
irrigating solution, is FDA approved
for use during cataract surgery or IOL
replacement to maintain pupil size by
preventing intraoperative miosis and
to reduce postoperative ocular pain. It’s
the first commercially available prod-
uct from the Omeros PharmacoSurgery
platform, the idea of which is to
address the consequences of surgical-
site trauma (pain and the release of
prostaglandins causing miosis) pre-
emptively during surgery rather than
being forced to handle them intraop-
eratively and postoperatively. In the
setting of cataract surgery, Omidria
is a new way to improve the surgeon
and patient experience, and potentially
outcomes, via something that is under
the surgeon’s control — rather than the
patient’s. In October 2014, the Centers
for Medicare & Medicaid Services
(CMS) determined that Omidria
qualifies as a pass-through drug under
the Outpatient Prospective Payment
System. As a result, effective Jan. 1,
2015, ASCs can bill Medicare $465
per single-patient-use vial of Omidria.
This pass-through remains in effect for
2 to 3 years.
Omidria is one option following the
trend away from patient drop therapy
and toward novel methods of drug
delivery, as are the Dex-Moxi Dr. Mah
uses, and agents such as Tri-Moxi (tri-
amcinolone-moxifloxacin, Imprimis)
and Tri-Moxi-Vanc (triamcinolone-
moxifloxacin-vancomycin, Imprimis).
These proprietary compounded for-
mulations are available as single,
injectable doses to be administered
transzonularly at the conclusion of
ocular surgery. In a recent investigator-
initiated study that prospectively com-
pared rates of post-op CME between
a traditional steroid and NSAID drop
regimen and Tri-Moxi-Vanc com-
bined with a post-op NSAID drop, the
post-op CME rate was 1.5% in the tradi-
tional group (n=600) versus 0.5% in the
Tri-Moxi-Vanc plus post-op NSAID
drop group (n=600) (p=0.003).19
According to CMS policy, Tri-
Moxi and Tri-Moxi-Vanc aren’t eli-
gible for separate reimbursement for
surgeons or ASCs. Based on a recent
analysis conducted by Andrew Chang
& Co, Imprimis asserts that if the
policy were changed to allow cataract
surgery patients to choose and pay
for the dropless options, Medicare,
Medicaid, and patients would save
$2.1 to $13 billion between 2016 and
2025, with savings most likely around
$8.7 billion.20 The company says it plans
to devote time and other resources to
seeking reimbursement and patient pay
opportunities for these products. n
References
1. ESCRS Endophthalmitis Study Group, European Society of Cataract & Refractive Surgeons. Prophylaxis of postoperative endophthalmitis following cataract surgery: results of the ESCRS multicenter study and identification of risk factors. J Cataract Refract Surg. 2007;33(6):978-988.
2. Chang DF, Braga-Mele R, Mamalis N, et al.; ASCRS Cataract Clinical Committee. Prophylaxis of postopera-tive endophthalmitis after cataract surgery: results of the 2007 ASCRS member survey. J Cataract Refract Surg. 2007;33(10):1801-1805.
3. Chang DF, Braga-Mele R, Henderson BA, Mamalis N, Vasavada A; ASCRS Cataract Clinical Committee. Antibiotic prophylaxis of postoperative endophthalmitis after cataract surgery: Results of the 2014 ASCRS member survey. J Cataract Refract Surg. 2015;41(6):1300-1305.
4. Shorstein NH, Winthrop KL, Herrinton LJ. Decreased postoperative endophthalmitis rate after institution of intra-cameral antibiotics in a Northern California eye department. J Cataract Refract Surg. 2013;39(1):8-14.
5. Creuzot-Garcher C, Benzenine E, Mariet AS, et al. Inci-dence of acute postoperative endophthalmitis after cataract surgery: A nationwide study in France from 2005 to 2014.
Ophthalmology. 2016;123(7):1414-1420.
6. Herrinton LJ, Shorstein NH, Paschal JF, et al. Comparative effectiveness of antibiotic prophylaxis in cataract surgery. Ophthalmology. 2016;123(2):287-294.
7. Jabbarvand M, Hashemian H, Khodaparast M, Jouhari M, Tabatabaei A, Rezaei S. Endophthalmitis occurring after cataract surgery: outcomes of more than 480,000 cataract surgeries, epidemiologic features, and risk factors. Ophthalmology. 2016;123(2):295-301.
8. Schwartz SG, Flynn HW, Grzybowski A, Relhan N, Ferris FL. Intracameral antibiotics and cataract surgery: endo-phthalmitis rates, costs, and stewardship. Ophthalmology. 2016;123(7):1411-1413.
9. Haripriya A, Chang DF, Namburar S, Smita A, Ravindran RD. Efficacy of intracameral moxifloxacin endophthalmi-tis prophylaxis at Aravind Eye Hospital. Ophthalmology. 2016;123(2):302-308.
10. Witkin AJ, Shah AR, Engstrom RE, et al. Postoperative hemorrhagic occlusive retinal vasculitis: expanding the clinical spectrum and possible association with vancomycin. Ophthalmology. 2015;122(7):1438-1451.
11. American Society of Cataract and Refractive Surgery. ASCRS Clinical Survey 2014. Available online: http://www.globaltrendsinophthalmology.com/sites/default/files/2014%20ASCRS%20Clinical%20Survey%20supple-ment.pdf. Accessed July 7, 2016.
12. Kim SJ, Schoenberger SD, Thorne JE, Ehlers JP, Yeh S, Bakri S. Topical nonsteroidal anti-inflammatory drugs and cataract surgery: a report by the American Academy of Oph-thalmology. Ophthalmology. 2015;122(11):2159-2168.
13. Wittpenn JR, Silverstein S, Heier J, Kenyon KR, Hunkeler JD, Earl M; Acular LS for Cystoid Macular Edema (ACME) Study Group. A randomized, masked comparison of topical ketorolac 0.4% plus steroid vs steroid alone in low-risk cataract surgery patients. Am J Ophthalmol. 2008;146(4): 554-560.
14. Shorstein NH, Liu L, Waxman MD, Herrinton LJ. Compara-tive effectiveness of three prophylactic strategies to prevent clinical macular edema after phacoemulsification surgery. Ophthalmology. 2015;122(12):2450-2456.
15. McColgin AZ, Raizman MB. Efficacy of topical diclofenac in reducing the incidence of postoperative cystoid macular edema. Invest Ophthalmol Vis Sci. 1999;40:289.
16. Kessel L, Tendal B, Jørgensen KJ, et al. Post-cataract prevention of inflammation and macular edema by steroid and nonsteroidal anti-inflammatory eye drops: a systematic review. Ophthalmology. 2014;121(10):1915-1924.
17. Wielders LH, Lambermont VA, Schouten JS, et al. Preven-tion of cystoid macular edema after cataract surgery in nondiabetic and diabetic patients: a systematic review and meta-analysis. Am J Ophthalmol. 2015;160(5):968-981.
18. Wolf EJ, Braunstein A, Shih C, Braunstein RE. Incidence of visually significant pseudophakic macular edema after uneventful phacoemulsification in patients treated with nepafenac. J Cataract Refract Surg. 2007;33(9):1546-1549.
19. Imprimis Pharaceuticals. Clinical Study of Impri-mis Pharmaceuticals’ Tri-Moxi-Vanc Dropless Therapy Formulation Show Statistically Significant Reduction in Cystoid Macular Edema in Patients Following Cataract. Available online: http://imprimispharma.investorroom.com/2016-05-12-Clinical-Study-of-Imprimis-Pharmaceuticals-Tri-Moxi-Vanc-Dropless-Therapy-Formulation-Show-Statis-tically-Significant-Reduction-in-Cystoid-Macular-Edema-in-Patients-Following-Cataract-Surgery. Accessed July 7, 2016.
20. Andrew Chang & Co, LLC. Analysis of the Economic Impacts of Dropless Cataract Therapy on Medicare, Medicaid, State Governments, and Patient Costs. Available online: http://www.improvedeyecare.org/CSIE_Dropless_Economic_Study.pdf. Accessed July 7, 2016.
TO READ MORE ABOUT DROPLESS CATARACT SURGERY CODING,
SEE CODING & COMPLIANCE ON PAGE 32