Published in Cataract

The Ophthalmology Resident's Guide to Dropless Cataract Surgery

This is editorially independent content
18 min read
Review recent advancements in dropless cataract surgery ophthalmology residents can keep in mind to ensure optimal surgical outcomes.
The Ophthalmology Resident's Guide to Dropless Cataract Surgery
Cataract surgery is the most commonly performed surgery in the United States, with 3.7 million procedures performed annually.1
Surgical techniques have advanced significantly over the past several decades, from the advent of phacoemulsification to the improvement of implantable lenses.
These advances have significantly improved patients’ visual outcomes and have decreased costs and reduced complication rates for tens of millions of patients.

The burden of a post-operative protocol

As with any surgical procedure, cataract surgery requires that patients follow a prescribed post-surgical treatment plan designed to optimize the healing process and prevent post-operative infection and inflammation.
Though the specifics of post-operative medical management vary between practices, most post-operative treatment regimens consist of a combination of topical eye drops, including antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and steroids.2 Notably, while operative technology and techniques have improved dramatically in the past several decades, in the US, these post-operative regimens have remained largely unchanged for the past 50 years.3
These drop regimens can present serious burdens, especially with patients that rely on caregivers for medication management, as is the case for many pediatric and geriatric patients. Fortunately, with recent advances in drug delivery providing treatment options with more favorable pharmacokinetic properties, surgeons now have the ability to provide post-operative infection and inflammation prophylaxis with the use of fewer or even no eye drops.
This advancement has the potential to provide numerous benefits to both patients and providers, improving surgical outcomes, improving adherence, decreasing costs, and boosting patient satisfaction while streamlining post-operative medical management at the same time.

What’s currently available in cataract surgery?

The primary risks being medically managed following cataract surgery are infection, inflammation, pain, and cystoid macular edema (CME). In today’s diverse practice environment, there are a variety of options that surgeons can use to cut down on patients’ drop burden while also managing these risks in the post-operative period.

Topical antibiotics

Bacterial infection prophylaxis has historically been accomplished by using topical antibiotic eye drops, commonly fluoroquinolones or cephalosporins. However, in recent years, alternatives to eye drops have been developed which have greater intraocular penetration and longer duration of effect than is achievable using topical drops. Intracameral antibiotics can be easily administered toward the end of cataract surgery and have been associated with significant declines in rates of postoperative endophthalmitis in several large studies in the EU, the US, and Japan.4-6
The most robust of these studies was a prospective, randomized trial assigning 16,603 patients across Europe to receive intracameral cefuroxime, topical levofloxacin, or both. The absence of intracameral cefuroxime was associated with a nearly 5-fold increase in endophthalmitis rates, an effect size that was so large that the trial was stopped early by the ethics committee.7
The use of topical antibiotic drops in addition to intracameral antibiotics did not add any additional benefit in risk reduction in any of these studies. Intravitreal antibiotics delivered via pars plana or transzonular injection have also been shown to be effective in preventing post-operative endophthalmitis, with several studies indicating noninferiority with topical drop therapy.8,9

Anti-inflammatories

Anti-inflammatory medications are also typically used following cataract surgery in order to prevent post-operative pain, inflammation, and CME. This is usually accomplished using a tapering regimen of topical steroid drops, sometimes with the addition of topical NSAID drops. However, there are now other formulations of these medications available which can reduce the drop burden while sustaining therapeutic drug levels.
One approach is to use a dexamethasone-eluting punctal insert which is able to deliver a tapering dose of corticosteroid to the ocular surface for up to 30 days before biodegrading. This punctal insert can be placed before, during, or after an operation and is able to be easily visualized or removed throughout its lifetime.

Compounded formulations

Another approach is to use a compounded formulation of intracameral phenylephrine and ketorolac intra-operatively in order to prevent excessive miosis during the operation as well as to prevent post-operative pain and CME.10
Also available for post-operative inflammation control are intravitreal injections of corticosteroid suspensions. These suspensions are designed to be delivered into the posterior chamber at the end of cataract surgery either through a pars plana or transzonular approach and are usually compounded along with antibiotics.
Table 1 outlines examples of products with compounded formulations.
Intraocular FormulationsCorticosteroidAntibioticNSAIDAlpha-agonist
INTRACAMERAL
Dex-Moxi0.1% dexamethasone phosphate0.5% moxifloxacin
Dex-Moxi-Ketor0.1% dexamethasone phosphate0.5% moxifloxacin0.4% ketorolac
Phenylephrine-ketorolac0.3% ketorolac1% phenylephrine
Cefuroxime1.0mg/0.1mL
Moxifloxacin0.15-0.5mg/0.1mL
Vancomycin1.0mg/0.1mL
INTRAVITREAL
Tri-Moxi1.5% triamcinolone acetonide0.1% moxifloxacin
Tri-Moxi-Vanc1.5% triamcinolone acetonide0.1% moxifloxacin + 1% vancomycin
Table 1: Courtesy of authors.

Benefits of dropless cataract surgery

Dropless cataract surgery is a paradigm shift that offers numerous benefits for both patients and providers, including reduced complication rates, improved adherence, decreased costs, and improved patient satisfaction.

Reduced rates of endophthalmitis

Post-operative endophthalmitis is a rare but vision-threatening risk of cataract surgery. The use of intracameral antibiotic therapy has been associated in numerous studies with decreased rates of postoperative endophthalmitis when compared with drop therapy alone.
In the 2021 American Academy of Ophthalmology (AAO) Cataract in the Adult Eye Preferred Practice Pattern, the authors of the report concluded that, “There is substantial evidence that intracameral antibiotic administration reduces the risk of postoperative bacterial endophthalmitis. Increasing evidence also suggests that topically applied antibiotics do not add to the benefit of intracameral injection.”11
In many developed countries outside the US, such as France, the UK, Sweden, and Denmark, intracameral antibiotic administration has become the standard of care.12 Intravitreal antibiotic administration is another promising approach for infection prophylaxis, though it has not been studied in trials as large and comprehensive as those conducted with intracameral antibiotics.

Decreased incidence of human error

By making infection and inflammation prophylaxis a matter of management by the surgeon, dropless cataract surgery obviates the risk of human error in scheduling and administering eye drops correctly.
There is a significant unmet need for this, given that in one study of patient eye drop administration technique, over 90% of patients observed showed an improper administration technique, whether contaminating the bottle tip, contacting the ocular surface directly with the bottle tip, or even missing their eye completely.13
Additionally, dropless cataract surgery presents an opportunity to reduce caregiver burdens for patients that are unable to administer eye drops themselves, such as patients with a tremor, dementia, or arthritis.

Increased efficiency

Dropless therapy can be convenient for practices to implement, helping surgeons save on scarce time and resources. The complexity of post-operative drop therapy can present a daunting challenge to patients and caregivers, who often need to call a medication helpline for advice on dosing schedules, guidance about irritation from eye drops, or troubleshooting problems with pharmacies. By removing drops from routine post-operative management, busy surgical practices can improve their efficiency and prevent negative patient experiences after otherwise successful surgeries.
Dropless techniques are also designed to be easy to implement, using routes of administration that are familiar or easy to access for most practicing ophthalmologists. In one physician survey studying the implementation of the intracanalicular dexamethasone-eluting insert across 23 US surgical sites, physicians reported feeling comfortable administering the insert after a mean of three placements, with a majority of physicians indicating that they preferred the implant over drops to manage post-surgical pain and inflammation.14

A more economical approach to cataract surgery

Dropless therapies can be significantly cheaper for both patients and payors. In a cost-effectiveness analysis, intracameral therapy was found to be significantly more cost-effective than topical fluoroquinolones in preventing endophthalmitis.15
A 2015 report commissioned by Cataract Surgeons for Improved Eyecare (partially funded by Imprimis Pharmaceuticals, a manufacturer of some intravitreal antibiotic suspensions), determined using Centers for Medicare and Medicaid Services (CMS) data that universal adoption of dropless therapy would cost as much as 77% lower than traditional drop therapy, with overall savings by CMS of approximately $7.1 billion over a 10 year period.16
By eliminating the need for patients to purchase eye drop medications from the pharmacy, dropless treatment modalities would also eliminate the copay that patients with Medicare would be expected to pay.

Potential drawbacks of dropless cataract surgery

As with any new treatment modality, dropless cataract surgery comes with a set of risks and drawbacks that are important to be aware of so that individual patients can be matched with their ideal personalized treatment plan.
Both the dexamethasone-eluting intracanalicular implant and the intravitreal steroid suspensions were compared in their phase 3 trials with placebo. As a result, there is a paucity of data comparing these sustained-release anti-inflammatory products with topical steroid therapy. This makes it difficult to draw definitive conclusions regarding their comparative efficacy.
To date, there is no FDA-approved antibiotic specifically formulated for intracameral use in the United States.11 As a result, antibiotics intended for intracameral use must be compounded either by strictly regulated 503B outsourcing facilities, by more loosely regulated 503A compounding pharmacies, or on-site. Compounding using less standardized means may result in dilution errors which could potentially result in toxicity or insufficient concentration, so the use of pre-prepared medications is recommended.

Hemorrhagic occlusive retinal vasculitis

In several instances at different medical centers, intraocular vancomycin has been associated with occurrences of hemorrhagic occlusive retinal vasculitis (HORV), a rare ischemic retinal condition leading to hemorrhage and vision loss.17 Due to this risk, the routine use of intraocular vancomycin is discouraged following cataract surgery according to AAO practice guidelines.11

Retinal detachment

Regardless of the benefits of cutting down on drop burdens, intravitreal injections are not without risk. Pars plana intravitreal injections have a small risk of causing retinal detachment and hemorrhage, and using a transzonular approach risks damaging the zonules and causing subsequent lens decentration following cataract surgery, especially in patients with pseudoexfoliation syndrome.18

Increased intraocular pressure

There is also a risk of increased intraocular pressure (IOP) from the use of some dropless cataract surgery techniques, both from the direct injection of medication into the globe and from the effect of potentially higher and longer-lasting intraocular concentrations of steroid compounds.
Data is encouraging regarding IOP increases; in one retrospective review of intravitreal injections of triamcinolone-moxifloxacin-vancomycin (TMV) following cataract surgery, the authors found that 0.9% of cases resulted in a 10mmHg increase either at days 14 to 21 or day 90 following injection.19
Low-dose (3mg) triamcinolone acetate intracameral and intravitreal injections following cataract surgery resulted in fewer patients experiencing IOP spikes than with post-operative steroid drops.20 A preliminary investigation of the dexamethasone-eluting intracanalicular insert was also encouraging regarding IOP increases, with only one patient in 30 experiencing an IOP elevation of more than 10mmHg, a rate comparable to that of the placebo group.21

Toxic anterior segment syndrome

Toxic anterior segment syndrome (TASS) is a sterile post-operative inflammatory reaction that can occur after the introduction of an offending substance in the anterior segment. The appearance of TASS can be dramatic, with diffuse corneal edema, significant cell flare, and hypopyon.
The exact agents that cause TASS are unknown, but the syndrome tends to occur in clusters, at least one of which was associated with the use of intracameral cefuroxime.22 To date, there is no known systematic association of intracameral cefuroxime with TASS despite widespread international use, but it remains a risk to be cognizant of when administering intracameral medications.

Cost considerations with dropless contact surgery

Current CMS reimbursement policy may also contribute to the slow adoption of dropless cataract surgery in the United States.16 Presently, CMS pays a set amount to providers for a given surgery, with which they are expected to pay for staffing and materials. With traditional drop therapy, patients purchase their medications from pharmacies and are expected to pay a 20% copay for Medicare patients and a $1 copay for Medicaid patients, with the remainder being paid for by CMS.
With dropless therapy, there is no need for these medications to be used, and patients are not required to pay for them. Rather, the cost of acquiring these medications is attributed to facility costs incurred during the surgery and is expected to be covered by the medical provider, without additional reimbursement by CMS. This may have a deleterious effect on the adoption of dropless techniques, as they are more expensive for providers under the current CMS policy, even though they may reduce costs to the medical system overall.15,16
If CMS changes its policy to reimburse physicians for costs incurred for procurement of dropless therapies, this barrier to use would be rendered obsolete and further adoption of dropless techniques may be more easily encouraged in more financially vulnerable practices.

Conclusions

Dropless cataract surgery represents an evolving and exciting opportunity for cataract surgeons to improve the post-operative experience of their patients. The US marketplace has numerous options to choose from in order to provide the optimal solutions to meet the needs of individual patients, with no clear choice being superior to all others. These options are diverse, including intracameral antibiotics and anti-inflammatories, intravitreal suspensions of antibiotics and anti-inflammatories, and an intracanalicular anti-inflammatory insert.
Dropless therapy has the potential to provide numerous benefits to patients and providers, including reduced adverse events, improved convenience, improved medication adherence, and lower costs for payers and patients. Challenges still remain before dropless therapy is more widely adopted in the US, including a lack of definitive data comparing different anti-inflammatory treatment modalities, the existence of several rare complications associated with the use of some intraocular drug formulations, and the structure of current CMS policy surrounding reimbursement for cataract surgeries.
As new data emerge and regulatory practices continue to evolve, it will be important for cataract surgeons to remain up to date with new developments which could help improve the post-operative medical management of their patients.
  1. Rossi T, Romano MR, Iannetta D, et al. Cataract surgery practice patterns worldwide: a survey. BMJ Open Ophthalmol. 2021;6(1):e000464.
  2. Zafar S, Wang P, Schein OD, et al. Prescribing Patterns and Costs Associated with Postoperative Eye Drop Use in Medicare Beneficiaries Undergoing Cataract Surgery. Ophthalmology. 2020;127(5):573-581.
  3. Assil KK, Greenwood MD, Gibson A, et al. Dropless cataract surgery: modernizing perioperative medical therapy to improve outcomes and patient satisfaction. Curr Opin Ophthalmol. 2021;32 Suppl 1:S1-s12.
  4. Endophthalmitis Study Group, European Society of Cataract and 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.
  5. Herrinton LJ, Shorstein NH, Paschal JF, et al. Comparative Effectiveness of Antibiotic Prophylaxis in Cataract Surgery. Ophthalmology. 2016;123(2):287-294.
  6. Matsuura K, Miyoshi T, Suto C, et al., Efficacy and safety of prophylactic intracameral moxifloxacin injection in Japan. J Cataract Refract Surg. 2013;39(11):1702-1706.
  7. 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. Journal of Cataract & Refractive Surgery. 2007;33:978–988.
  8. Nassiri S, Hwang FS, Kim J, et al. Comparative analysis of intravitreal triamcinolone acetonide-moxifloxacin versus standard perioperative eyedrops in cataract surgery. J Cataract Refract Surg. 2019;45(6):760-765.
  9. Kuriakose RK, Cho S, Nassiri S, et al. Comparative Outcomes of Standard Perioperative Eye Drops, Intravitreal Triamcinolone Acetonide-Moxifloxacin, and Intracameral Dexamethasone-Moxifloxacin-Ketorolac in Cataract Surgery. J Ophthalmol. 2022;2022:4857696.
  10. Visco DM, Bedi R. Effect of intracameral phenylephrine 1.0%-ketorolac 0.3% on postoperative cystoid macular edema, iritis, pain, and photophobia after cataract surgery. J Cataract Refract Surg. 2020;46(6):867-872.
  11. Miller KM, Oetting TA, Tweeten JP, et al. Cataract in the Adult Eye Preferred Practice Pattern. Ophthalmology. 2022;129(1):P1-p126.
  12. Javitt, J.C., Intracameral Antibiotics Reduce the Risk of Endophthalmitis after Cataract Surgery: Does the Preponderance of the Evidence Mandate a Global Change in Practice? Ophthalmology, 2016. 123(2): p. 226-231.
  13. An JA, Kasner O, Samek DA, et al. Evaluation of eyedrop administration by inexperienced patients after cataract surgery. J Cataract Refract Surg. 2014;40(11):1857-1861.
  14. Matossian C, Stephens JD, Rhee MK, et al. Early Real-World Physician Experience with an Intracanalicular Dexamethasone Insert. Clin Ophthalmol. 2022;16:2429-2440.
  15. Sharifi E, Porco TC, Naseri A. Cost-effectiveness analysis of intracameral cefuroxime use for prophylaxis of endophthalmitis after cataract surgery. Ophthalmology. 2009;116(10):887-896.
  16. Cataract Surgeons for Improved Eyecare. Analysis of the Economic Impacts of Dropless Cataract Therapy on Medicare, Medicaid, State Governments, and Patient Costs. October 2015. http://www.improvedeyecare.org/CSIE_Dropless_Economic_Study.pdf.
  17. Witkin AJ, Chang DF, Jumper JM, et al. Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: Clinical Characteristics of 36 Eyes. Ophthalmology. 2017;124(5):583-595.
  18. Kumar BV, Harun S, Prasad S. Trans-zonular delivery of intravitreal triamcinolone acetonide in the management of pre-existing macular oedema during cataract surgery. Acta Ophthalmol Scand. 2006;84(3):438-440.
  19. Tyson SL, Bailey R, Roman JS, et al. Clinical outcomes after injection of a compounded pharmaceutical for prophylaxis after cataract surgery: a large-scale review. Curr Opin Ophthalmol. 2017;28(1):73-80.
  20. Gills JP, Gills P. Effect of intracameral triamcinolone to control inflammation following cataract surgery. J Cataract Refract Surg. 2005;31(8):1670-1671.
  21. Walters T, Endl M, Elmer TR, et al. Sustained-release dexamethasone for the treatment of ocular inflammation and pain after cataract surgery. J Cataract Refract Surg. 2015;41(10):2049-2059.
  22. Çakır B, Celik E, Aksoy NA, et al. Toxic anterior segment syndrome after uncomplicated cataract surgery possibly associated with intracamaral use of cefuroxime. Clin Ophthalmol. 2015;9:493-497.
Brian Nazareth, MS
About Brian Nazareth, MS

Brian Nazareth is a fourth year medical student at the Boston
University School of Medicine in Boston, MA. He graduated summa cum laude at the University of Florida with a bachelors degree in
biomedical engineering and a concentration in neural engineering. He discovered a passion for ophthalmology while in medical school and is currently conducting research with the BUSM Department of
Ophthalmology and the Lions Eye Institute for Transplant and Research.

Aside from his medical interests, Brian enjoys wilderness backpacking, road biking, SCUBA diving, and exploring new restaurants and cafes in Boston.

Brian Nazareth, MS
Robin K. Kuriakose, MD
About Robin K. Kuriakose, MD

Dr. Robin Kuriakose is a board-certified and fellowship-trained cornea, cataract, and refractive surgeon. He completed his residency training at Loma Linda University Health in southern California and his fellowship training in Cornea and Refractive Surgery at Northwestern University in Chicago, where he was named Fellow of the Year. Dr. Kuriakose is passionate about mentorship, technology, and innovation. He has developed mobile applications and websites to aid fellow ophthalmologists as well as patients. Dr. Kuriakose is a New York native, but now practices in the Bay Area in California where he enjoys teaching local ophthalmology residents and other eye care providers.

Robin K. Kuriakose, MD
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