The proportion of Americans older than 65 years of age is growing rapidly, increasing both the incidence of age-related cataract and the demand for skilled surgeons. At the same time, cataract surgery has become increasingly safe and predictable. It’s no surprise, then, that patients and ophthalmologists alike have an interest in optimizing its efficiency and the perioperative patient experience. Two notable innovations born out of this trend include immediate sequential bilateral cataract surgery (ISBCS) and the optimization of postoperative drug delivery.
What is ISBCS?
Historically, the immediate bilateral approach was limited to patients who require general anesthesia or with physical or mental comorbidities, has been increasingly utilized nationally and internationally in otherwise routine cases.
As support for the general application of ISBCS grows, researchers have proposed detailed guidelines to establish specific protocols and ensure safety and reliability. For instance, the International Society of Bilateral Cataract Surgeons, among other professional societies, advise treating each eye as a separate and individual surgery.1 This requires surgical teams to use completely separate instrumentation trays, drapes, and personal protective equipment along with different lot numbers for pharmaceuticals and viscoelastics. Therefore, if a complication occurs in one eye, such as postoperative endophthalmitis (PE) or toxic anterior segment syndrome (TASS), the risk of bilateral presentation is reduced. A comprehensive patient selection process is also paramount.
A recent meta-analysis found that, while both ISBCS and conventional delayed sequential bilateral cataract surgery (DSBCS) improve a patient’s visual function and quality of life, ISBCS can offer additional unique benefits to the individual and the broader healthcare infrastructure.2
For the individual, ISBCS offers a faster path to visual rehabilitation. This is not simply a matter of convenience — waiting periods may increase patient’s risks of falls and hospitalizations.3 They will require less time away from work or school for both patients and their caretakers, and a reduced burden of securing transportation.
Finally, these patients benefit by avoiding the anisometropia which may otherwise occur during the waiting period between eyes. Overall, patients report high rates of satisfaction with ISBCS.4
For the provider, improved operating room efficiency and fewer patient visits to the clinic can augment an ophthalmologist’s capacity to care for patients. A 2001 publication found ISBCS only added 12 minutes to the usual cataract time of 28 minutes, proportionally increasing the amount of time spent caring for patients’ eyes.5 These improvements can be particularly impactful for underserved populations in vision services-deficient areas, allowing providers to examine significantly more patients while minimizing barriers to access for the patient population. It is not surprising that ISBCS has been described in surgical outreach camps as an effective means of expanding volume.6
However, ISBCS really shines as a potent means to reduce associated costs of ocular care. An economic cost-minimization analysis predicted a savings of nearly $522 million to the Medicare program if 75% of eligible patients selected ISBCS over DSBCS in the United States.7 If time, transportation, and lost productivity are factored in, these savings increased to $783 million.
ISBCS Pitfalls: Safety Concerns and Reimbursement
The leading safety concerns limiting widespread ISBCS adoption are well characterized by a 2018 survey study of cataract surgeons within the Kaiser Permanente Northern California health system who have the opportunity but elect not to perform ISBCS.8 The most cited concerns were the loss of postoperative refraction from the first eye to guide the second eye (80%) and risk of bilateral vision loss (73%), such as from postoperative endophthalmitis (PE) or toxic anterior segment syndrome (TASS).
The former concern hinges on the presumption that a postoperative refraction of a patient’s first eye can effectively improve the outcome for that patient’s second eye, particularly if there is substantial ametropia. This concern may be of less importance in the era of advanced ocular biometric devices and newer generation intraocular lens (IOL) power calculation formulas. In fact, a recent retrospective study compared 13,711 DSCBS and 3561 ISBCS Kaiser Permanente patients and found no significant differences in BCVA or refractive error between the 2 patient groups.9 Nonetheless, patients at a high risk of refractive surprise, and those at risk for dysphotopsia or dissatisfaction with presbyopia-correcting IOLs, may do best with DSCBS.
The latter concern – bilateral vision loss due to PE or TASS – appears to be exceedingly rare, especially with the inclusion of intracameral antibiotics. In the past 60 years, only 4 reported cases of bilateral endophthalmitis have been reported and all 4 were related to breaches in aseptic protocol.10 A recent large cohort study examining 95,606 ISBCS cases found that, when providers followed appropriate aseptic technique, the risk of postoperative endophthalmitis was no greater than in unilateral cataract surgery.10 When providers utilized intracameral antibiotics, the risk decreased substantially from 1 in 5759 to 1 in 14,352 cases.10 However, more expansive trials on this topic are needed to convince ophthalmologists of the safety of ISBCS and its viability in daily surgical practice.
Arguably the largest barrier for the widespread adoption of ISBCS in the US is the significantly lower reimbursement rate for the second eye under a traditional fee-for-service Medicare program.
Postoperative Drug Delivery – Can We Do Better?
Although cataract surgery has evolved tremendously in the recent decades, infection and inflammation management has largely remained unchanged.11 Topical formulations are considered routine, but patients frequently contend with difficulties in adherence, self-administration, and costs. The development of compounded, intraocular, and sustained release formulations can augment existing efforts to improve patient comfort and adherence. This section outlines advances for simplified delivery of antibiotics, steroid, and nonsteroidal anti-inflammatories (NSAIDs).
ICAs and Cataracts
Recently, intracameral antibiotics (ICAs) have gained significant favor among physicians globally. A recent 2021 ASCRS survey of more than 1200 cataract surgeons found nearly 66% were utilizing intracameral prophylaxis, an increase when compared with 2014 and 2007 (50% and 33% respectively).12
A prominent randomized control trial (RCT) conducted by the European Society of Cataract and Refractive Surgeons (ESCRS) randomly assigned 13,689 patients and observed intracameral cefuroxime to be of such superior benefit, they ended the study early to report the results. In groups not receiving intracameral cefuroxime prophylaxis, the incidence of endophthalmitis was nearly 5 times as high.13 These correlations were observed by several meta-analyses which found intracameral antibiotics, particularly cefuroxime, to be more effective at preventing endophthalmitis than their topical counterparts.14,15
However, there remain concerns regarding the safety of ICAs. Hemorrhagic occlusive retinal vasculitis (HORV) has been described as a rare but devastating complication associated with intraocular vancomycin usage, while toxic anterior segment syndrome (TASS) has been reported with intracameral moxifloxacin and cefuroxime.16-18 These findings, however, are difficult to extrapolate appropriately due to the inherent heterogeneity of these studies.
A standardized FDA-approved ICA formulation would go a long way to improve utilization. Eighty percent of respondents to the 2021 ASCRS survey reported that the development of a commercially approved ICA is important, and 93% reported that they would use ICAs if such a product was readily available and reasonably priced. Certainly, large scale, multicenter RCTs evaluating the efficacy of multiple ICAs are necessary to generate confidence among providers and patients alike.
Extended-Release Steroid Formulations
Two extended-release steroids applicable to patients undergoing cataract removal have been approved by the FDA; An intracanalicular insert, Dextenza (Ocular Therapeutix) and an intraocular suspension, Dexycu (EyePoint Pharmaceuticals).
Both formulations have demonstrated encouraging anti-inflammatory effects. A phase 3 trial examining Dexycu found resolution of anterior chamber cells at approximately 8 days after surgery in 66% of patients.19
Separately, 2 trials of Dextenza found AC cell resolution 14 days after surgery in 33% and 52% of enrolled patients respectively.20,21
Subconjunctival triamcinolone injections are an alternative, low-cost approach to sustained release steroid delivery, although its use remains off-label.
Omidria (Rayner), a phenylephrine 1%/ketorolac 0.3% combination, is an FDA-approved NSAID-combination drug that is irrigated through the eye with cataract surgery to limit intraoperative miosis and improve patient’s postoperative pain. A multicenter trial shows Omiridia can significantly reduce postoperative pain when compared with a placebo and noted no significant complications.22
Another combination drop formulation, LessDrops™ (ImprimisRX) – comprised of prednisolone acetate, gatifloxacin hydrochloride, and bromfenac – has shown similar efficacy to a traditional multiple drop regimen, according to a 2020 study.23 Other combination formulations such as OMNI™(OSRX) may provide similar benefits. This will hopefully be the first of many trials evaluating the potential and safety of compounded drops.
The demand for cataract surgery has been steadily increasing in recent years, exerting significant strains on medical systems, all while healthcare provider shortages loom. Our aging cataract patient population may encounter difficulty managing this present challenging and burdensome process. Ophthalmologists and their partners in industry must take deliberate and organized steps through advocacy and research to ensure both the safety and efficacy of our patients’ cataract surgical journeys. These include ISBCS, optimizing postoperative drug delivery, co-management with optometry, and utilization of telemedicine and other digital resources, amongst other strategies.
Dr Mulpuri is a corneal research fellow at Bascom Palmer Eye Institute. Dr Mulpuri has no relevant financial disclosures. Dr Tonk is a cornea, cataract, and refractive surgeon and an associate medical director and cornea fellowship co-director at Bascom Palmer Eye Institute, University of Miami Miller School of Medicine. Dr Tonk has a financial interest in LayerBio, whose lead candidate, OcuRing™, is a bio erodible sustained-release implant for use in cataract surgery.
- International Society of Bilateral Cataract Surgeon (iSBCS) SBCS General Principles for Excellence in ISBCS 2009 Spain iSBCS 2009
- Malvankar-Mehta MS, Chen YN, Patel S, Leung AP, Merchea MM, Hodge WG. Immediate versus delayed sequential bilateral cataract surgery: a systematic review and meta-analysis. PLoS One. 2015;10(6):e0131857. doi:10.1371/journal.pone.0131857
- Feng YR, Meuleners LB, Fraser ML, Brameld KJ, Agramunt S. The impact of first and second eye cataract surgeries on falls: a prospective cohort study. Clin Interv Aging. 2018;13(8):1457-1464. doi:10.2147/CIA.S164419
- Serrano-Aguilar P, Ramallo-Fariña Y, Cabrera-Hernández JM, et al. Immediately sequential versus delayed sequential bilateral cataract surgery: safety and effectiveness. J Cataract Refract Surg. 2012;38(10):1734-1742. doi:10.1016/j.jcrs.2012.05.024
- Smith GT, Liu CS. Is it time for a new attitude to “simultaneous” bilateral cataract surgery? Br J Ophthalmol. 2001;85(12):1489-1496. doi:10.1136/bjo.85.12.1489
- Giles K, Robert ES, Come EM, Wiedemann P. Simultaneous bilateral cataract surgery in outreach surgical camps. Ophthalmol Eye Dis. 2017;9:1179172117701738. Published 2017 Apr 20. doi:10.1177/1179172117701738
- Neel ST. A cost-minimization analysis comparing immediate sequential cataract surgery and delayed sequential cataract surgery from the payer, patient, and societal perspectives in the United States. JAMA Ophthalmol. 2014;132(11):1282-1288. doi:10.1001/jamaophthalmol.2014.2074
- Amsden LB, Shorstein NH, Fevrier H, Liu L, Carolan J, Herrinton LJ. Immediate sequential bilateral cataract surgery: surgeon preferences and concerns. Can J Ophthalmol. 2018;53(4):337-341. doi:10.1016/j.jcjo.2017.10.034
- Herrinton LJ, Liu L, Alexeeff S, Carolan J, Shorstein NH. Immediate sequential vs. delayed sequential bilateral cataract surgery: retrospective comparison of postoperative visual outcomes. Ophthalmol. 2017;124(8):1126-1135. doi:10.1016/j.ophtha.2017.03.034
- Arshinoff SA, Bastianelli PA. Incidence of postoperative endophthalmitis after immediate sequential bilateral cataract surgery. J Cataract Refract Surg. 2011;37(12):2105-2114. doi:10.1016/j.jcrs.2011.06.036
- Chang DF, Rhee DJ. Antibiotic prophylaxis of postoperative endophthalmitis after cataract surgery: results of the 2021 ASCRS member survey. J Cataract Refract Surg. 2022;48(1):3-7. doi:10.1097/j.jcrs.0000000000000757
- Barry P, Seal DV, Gettinby G, et al. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery: Preliminary report of principal results from a European multicenter study. 2006;32(5):709]. J Cataract Refract Surg. 2006;32(3):407-410. doi:10.1016/j.jcrs.2006.02.021
- Rana K, Bahrami B, van Zyl L, Esterman A, Goggin M. Efficacy of intracameral antibiotics following manual small incision cataract surgery in reducing the rates of endophthalmitis: A meta-analysis. Clin Exp Ophthalmol. 2021;49(1):25-37. doi:10.1111/ceo.13890
- Bowen RC, Zhou AX, Bondalapati S, et al. Comparative analysis of the safety and efficacy of intracameral cefuroxime, moxifloxacin and vancomycin at the end of cataract surgery: a meta-analysis. Br J Ophthalmol. 2018;102(9):1268-1276. doi:10.1136/bjophthalmol-2017-311051
- Witkin AJ, Chang DF, Jumper JM, et al. Vancomycin-associated hemorrhagic occlusive retinal vasculitis: clinical characteristics of 36 eyes. Ophthalmol. 2017;124(5):583-595. doi:10.1016/j.ophtha.2016.11.042
- Çakır B, Celik E, Aksoy NÖ, et al. Toxic anterior segment syndrome after uncomplicated cataract surgery possibly associated with intracamaral use of cefuroxime. Clin Ophthalmol. 2015;9:493-497. Published 2015 Mar 17. doi:10.2147/OPTH.S74249
- Donnenfeld ED, Solomon KD, Matossian C. Safety of IBI-10090 for inflammation associated with cataract surgery: Phase 3 multicenter study. J Cataract Refract Surg. 2018;44(10):1236-1246. doi:10.1016/j.jcrs.2018.07.015
- Lee A, Blair HA. Dexamethasone intracanalicular insert: a review in treating post-surgical ocular pain and inflammation. 2020 Aug;80(12):1265]. Drugs. 2020;80(11):1101-1108. doi:10.1007/s40265-020-01344-6
- Walters T, Bafna S, et al. Efficacy and safety of sustained release dexamethasone for the treatment of ocular pain and inflammation after cataract surgery: Results from two phase 3 studies. J Clin Exp Ophthalmol. Published online August 1, 2016. doi:10.4172/2155-9570.1000572
- Lawuyi LE, Gurbaxani A. The clinical utility of new combination phenylephrine/ketorolac injection in cataract surgery. Clin Ophthalmol. 2015;9(7):1249-1254. doi:10.2147/OPTH.S72321
- Solomon KD, Sandoval HP, Potvin R. Comparing combination drop therapy to a standard drop regimen after routine cataract surgery. Clin Ophthalmol. 2020;14(7):1959-1965.