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