Cheryl Guttman Krader, BS, Pharm

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For some, intraoperative aberrometry offers the opportunity for a more customized approach to IOL decisions and results in better outcomes, whereas others say it is not the optimal solution for achieving consistently better refractive accuracy.

‘Will be the future for achieving better outcomes because it uses a large dataset that can help catch outliers’

Intraoperative aberrometry will become standard in the future because it allows for a more customized approach to IOL decisions and results in better outcomes, said Robin R. Vann, MD. Results of large-scale studies from different countries show that after lens replacement surgery, surgeons are achieving a refractive outcome within 0.5 D of target only 55% to 80% of the time, he said.

“If we are going to do better, we need to think about the very long and very short eyes that are not modeled well in current IOL formulas and about eyes for which values of surgically induced astigmatism (SIA) and posterior corneal astigmatism (PCA) are far outside of the averages used for toric IOL calculations,” said Dr. Vann, medical director, Duke Eye Center Operating Rooms, Durham, NC.

“Intraoperative aberrometry will be the future for achieving better outcomes because it uses a large dataset that can help catch outliers, allows surgeons to incorporate SIA and PCA on a case-bycase basis, and enables outcome tracking and analysis for continued optimization of surgical constants,” he said.

Between 10% and 20% of eyes are outliers on the axial length distribution curve, and therefore, they represent a sizeable subgroup with which surgeons continue to struggle in trying to accurately select spherical IOL power. The ability to predictably minimize astigmatism is limited both by the use of average values for SIA and also PCA in toric IOL calculators.

“With small-incision cataract surgery, SIA can range from 0 to 1 D, but we are not measuring the actual value in each patient,” according to Dr. Vann. “Similarly, the mean magnitude of PCA has been reported to be 0.3 D, but it too can range from 0 to 1 D, and the variability is not accounted for on a case-by-case basis with the use of nomograms,” he said.

Dr. Vann reviewed two studies that showed the benefit of using intraoperative aberrometry for improving refractive surgery outcomes. A retrospective study by Cionni et al. analyzing data from more than 32,000 eyes found that the mean absolute prediction error was significantly lower with use of intraoperative aberrometry than without, 0.30 D versus 0.36 D.

Even more interesting were data from eyes in which intraoperative aberrometry recommended an IOL power different than the preoperative plan. In this subset, significantly more eyes had an aberrometry absolute prediction error of ≤0.5 D (81% versus 69%), Dr. Vann noted.

Use of intraoperative aberrometry for optimizing results with toric IOL implantation is supported by results from a study by Woodcock et al.

The study reported refractive astigmatism <0.5% D was achieved in 89% of eyes that had intraoperative aberrometry versus 76% of those for which power selection and alignment were guided by standard calculators and reference marks.

“Intraoperative aberrometry allows surgeons to adjust spherical power of the IOL before placing the implant and to customize toric IOL power and orientation to minimize the amount of residual astigmatism,” Dr. Vann said.

“In cases involving limbal-relaxing incisions, it also provides real-time feedback for adjusting the treatment and reducing astigmatism before the patient leaves the operating room,” he added.

Other benefits of intraoperative aberrometry come from the fact that it has a cloud-based database that serves as a resource for outcomes analysis.

“Surgeons who use the aberrometer can analyze how they are doing over time and compare their outcomes with those of surgeons around the world,” Dr. Vann said.

“With more than 1.2 million cases now entered, the system represents a huge database that can help surgeons improve the accuracy of their outcomes in outliers, and that is a real strength of the system,” he continued.

He also pointed out that intraoperative aberrometry is agnostic to lens model/manufacturer platforms.

“Using intraoperative aberrometry, surgeons are not tied to certain IOL technologies in order to get great outcomes,” Dr. Vann said.

‘Not the optimal solution for achieving consistently better refractive accuracy’

Intraoperative aberrometry has been shown to improve refractive outcomes after lens replacement surgery, but only in some studies. Although it may have particular value when surgeons perform more limited preoperative IOL calculations, it is not the optimal solution for achieving consistently better refractive accuracy, according to Douglas D. Koch, MD.

Defending the position that intraoperative aberrometry will not become standard in the future, he cited published reports about its performance and said that logic and practicality also argue against its routine use.

“The outcomes that can be achieved using advanced biometry on an optimized cornea and ever improving IOL formulas will always surpass those attainable with intraoperative aberrometry,” said Dr. Koch, professor and Allen, Mosbacher, and Law Chair in Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston.

Eyes with a history of laser refractive surgery present a particular challenge for achieving the refractive target after lens replacement surgery, and published studies investigating a potential benefit of intraoperative aberrometry have provided mixed results. One paper by Ianchulev et al. found that only 67% of 246 eyes achieved a postoperative refraction within 0.5 D of the predicted outcome, which is not very good, said Dr. Koch. Studies by Fram et al. and Fisher and Potvin reported that outcomes achieved with intraoperative aberrometry were neither better nor worse than those associated with the use of standard preoperative calculations.

Analyses of patients operated on at the Cullen Eye Institute also did not provide any evidence supporting the use of intraoperative aberrometry. Reviewing the data, Dr. Koch reported that in a series of 129 eyes with a history of myopic LASIK or PRK, the preoperative predicted IOL power differed from the intraoperative measurement in 97 eyes, of which 57 received an IOL based on intraoperative aberrometry and 40 were implanted according to the preoperative plan.

In the 57 eyes where the IOL was changed based on the intraoperative aberrometry, following guidance of the intraoperative tool turned out to be beneficial only about 50% of the time. In the 40 eyes where the selected IOL was not changed to follow the intraoperative aberrometry recommendation, the outcomes showed that following the preoperative plan was the better decision in about two-thirds of eyes.

“In other words, using the intraoperative aberrometry data in this subset of eyes would have hurt our results,” Dr. Koch said.

The findings were similar in an analysis of 65 eyes with a history of hyperopic LASIK or PRK. In that series, the IOL power suggested by the preoperative calculations differed from intraoperative aberrometry in 51 eyes. It was changed based on the aberrometry in 28 of the 51 eyes, but the switch resulted in an improved outcome only 50% of the time.

Looking at the 23 eyes where the results of intraoperative aberrometry and the preoperative planning differed and where the eyes were implanted according to the preoperative plan, staying with the original plan was the better decision in more than two-thirds of the cases.

“Again, our results would have been hurt had we followed the intraoperative aberrometry reading in all cases,” Dr. Koch said.

Studies investigating outcomes using intraoperative aberrometry in virgin eyes also report conflicting results, but overall their evidence weighs more against than in favor of intraoperative aberrometry, according to Dr. Koch.

Although a large retrospective study by Cionni et al. recently reported that a significantly higher percentage of eyes had an absolute prediction error ≤0.5 D using intraoperative aberrometry compared with conventional preoperative planning, 82% versus 76%, the 82% rate is lower than what can currently be achieved when surgeons use advanced biometry tools and the latest IOL formulas.

Two other studies focusing on virgin eyes found results using intraoperative aberrometry were no better than with preoperative calculations. Formulas such as the Barrett Universal 2, Hill RBF, and the Olsen ray-tracing formula are now giving us refractive outcomes that are within 0.5 D of target up to 90% of eyes or even more, he said.

The caveat, and an argument in favor of intraoperative aberrometry, is that this type of preoperative measurement requires extensive technician time and surgeon preoperative time analyzing all of the data, Dr. Koch said. Other studies of intraoperative ORA have focused on its use in guiding selection and alignment of toric IOLs.

A study by Woodcock et al. found intraoperative aberrometry outperformed standard power calculation as measured by the percentage of eyes achieving refractive astigmatism ≤0.5 D and comparison of mean residual astigmatism. In contrast, Solomon and Ladas reported a superior result using standard preoperative calculations supplemented with intraoperative markerless registration compared with intraoperative aberrometry.

The performance of intraoperative aberrometry is hampered by the fact that it is measuring a refraction on an eye that has received myriad drops with two or three incisions and sustained operative trauma. “The accuracy of our IOL calculations is still primarily limited by 1) our ability to predict the effective lens position, and 2) the accuracy of our corneal measurements,” Dr. Koch said.

“Essentially, intraoperative aberrometry is trying to predict the effective lens position on an altered eye. “We know that perfection in IOL calculation requires a pristine cornea, and without meeting that condition, intraoperative aberrometry has hit a ceiling in its accuracy, no matter how many datapoints go into its software to refine its performance,” he said.

Intraoperative aberrometry suffers from practical issues that can also serve to limit its adoption, he added.

“Intraoperative aberrometry is a wonderful tool that has served our patients well and will continue to do so for many practices,” Dr. Koch concluded. “However, it is expensive technology, and it, too, takes up surgeon time in the operating room.”

This article was adapted from Dr. Vann’s presentation at the 2018 meeting of the American Academy of Ophthalmology. Dr. Vann is a consultant to Alcon Laboratories.

This article was adapted from Dr. Koch’s presentation at the 2018 meeting of the American Academy of Ophthalmology. He is a consultant to Alcon, Carl Zeiss Meditec, and PerfectLens.

Articles

Robin R. Vann, MD, and Douglas D. Koch, MD, discuss the nuances of the procedure

Intraoperative aberrometry offers pros, cons for IOL surgical decisions

This article was reviewed by Yusen Huang, MD, PhD

Adding cefuroxime to the irrigating solution used during cataract surgery appears to be a safe and effective method for reducing the risk of postoperative endophthalmitis, according to researchers who reported their experience with this technique in a recently published retrospective study [Ma X, Zie L, Huang Y. 

The investigation included 61,299 eyes. Of the total cohort, 15,948 eyes were operated on between January 1, 2012 and December 31, 2014 using plain balanced salt solution (BSS) as the irrigating solution (control group), and 45,351 eyes underwent cataract surgery between January 1, 2015 and December 31, 2019 using irrigating solution that contained cefuroxime 1500 µg/mL. The mixture was prepared by withdrawing 10 mL BSS from the irrigating solution and injecting it into a vial of cefuroxime 750 mg. The reconstituted solution was injected back into the BSS container.

The rate of endophthalmitis was significantly decreased after the transition to intraoperative irrigation with cefuroxime. Endophthalmitis occurred in 11 eyes (0.07%) in the group that did not receive intraoperative cefuroxime and in 5 eyes (0.01%) when cefuroxime was used in the irrigating solution (

 < .01). Cultures were positive for bacteria in 4 of the 11 cases in the control group and in 1 of the 5 eyes in the intraoperative cefuroxime group (P >.05). There were no safety issues associated with intraoperative cefuroxime irrigation.

Discussing the research, Yusen Huang, MD, PhD, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, People’s Republic of China, said, “Although intracameral antibiotics are already widely accepted as a method for endophthalmitis prophylaxis in patients undergoing cataract surgery, the optimal choice of prophylactic routes and antibiotics are controversial. In European countries, commercial cefuroxime formulation (Aprokam) has been widely used and the dose administered is the same as in the European Society of Cataract and Refractive Surgeons (ESCRS) randomized prospective study demonstrating its efficacy. Elsewhere, however, surgeons have been reluctant to adopt intracameral cefuroxime because it is off-label and carries potential risks related to its two-step dilution process.”

“In our study, the manner of cefuroxime preparation was modified so that it involved only a one-step process, which makes it simpler, saves resources, and could reduce the potential risks of both preparation errors and contamination. Although the intracameral concentration achieved with our approach is estimated to be 1500 µg/mL, or only about 45% of the ESCRS recommendation, we found that it reduced the rate of postcataract surgery endophthalmitis by about seven-fold. Furthermore, during the last 2 years in our hospital where more than 25,000 cases of cataract surgery have been performed using intraoperative cefuroxime irrigation, not a single patient developed endophthalmitis. It should be noted, however, that this method is not recommended for use in patients with a history of vitrectomy considered the potential for rapid posterior segment diffusion of the antibiotic and potential macular toxicity.”

Although adding cefuroxime to the irrigating solution is still an off-label use of the medication, the authors suggested that it represents a good option for countries where there is no product that is licensed for intracameral use for endophthalmitis prophylaxis, and particularly in developing regions where the risks for both endophthalmitis and a poor outcome may be higher given a variety of contributory factors.

Throughout the entire study period, all patients received the same preoperative antisepsis with application of topical povidone-iodine. In addition, all patients started using topical levofloxacin 0.5% solution preoperatively and continued it postoperatively along with a topical steroid and topical nonsteroidal anti-inflammatory drug.

Postoperative follow-up visits were scheduled at 1 and 4 days, 4 weeks, and 12 weeks, but patients were instructed to seek care if they developed pain, redness, or loss of vision. The analyzed outcome was onset of acute-onset endophthalmitis, which was diagnosed if a patient presented within 6 weeks of surgery with eye pain, anterior chamber reaction or flare, hypopyon, and/or vitritis with causes for intraocular inflammation other than endophthalmitis excluded.

The 16 cases of endophthalmitis that were recorded during the 9-year study period developed at a median of 7.56 days after cataract surgery (range 1 to 21 days). None of the cases occurred in a patient who had an intraoperative complication or was noted to have incision leakage at the time endophthalmitis was identified.

Isolates from the culture-positive cases of endophthalmitis in the control group included 

 was identified as the causative pathogen in the culture-positive case of endophthalmitis among patients who received intraoperative cefuroxime, and the organism was found susceptible to cefuroxime.

Huang did not indicate any proprietary interest in the subject matter.

Findings from large retrospective study support intraoperative cefuroxime irrigation 

Preventing post-cataract surgery endophthalmitis

Results of a phase 2 trial suggest that dexamethasone cyclodextrin nanoparticle ophthalmic suspension 1.5% mg/mL (OCS-01, Oculis), a novel topical formulation of dexamethasone, has the potential to become the first once-daily and preservative-free topical corticosteroid for treating pain and inflammation after ocular surgery, said Eric D. Donnenfeld, MD, at the 2020 ASCRS virtual meeting.

Donnenfeld reported results from the SKYGGN study that randomly selected 153 patients 1:1:1 to treatment with OCS-01 once daily, OCS-01 twice daily, or vehicle for 14 days. The study met its primary endpoints analyzing absence of anterior chamber cells at postop day 15 and absence of ocular pain at postop day 4. There were no efficacy differences between the two OCS-01 dosing regimens and both were safe and well-tolerated.

“Inflammation and pain remain expected consequences of ocular surgery. Although available topical steroids are effective for treating these sequelae, potency and compliance with products that need to be used several times a day are major issues,” said Donnenfeld, a SKYGGN investigator who is clinical professor of ophthalmology, New York University Langone Medical Center, New York, and Founding Partner, Ophthalmic Consultants of Long Island and Connecticut, Garden City, NY. “Using a novel and proprietary nanoparticle formulation, OCS-01 was developed to deliver a potent anti-inflammatory effect and excellent safety profile with once-a-day dosing.”

Donnenfeld noted that the concentration of dexamethasone in OCS-01 is 15-fold greater than that found in commercially available topical dexamethasone suspension. In addition, the novel vehicle used for OCS-01 increases ocular surface residency time to hours compared with minutes using conventional dexamethasone 0.1% suspension. Furthermore, the proprietary nanoparticle technology enhances penetration of the active ingredient. As another benefit, the formulation is preservative-free.

A total of 20 US centers participated in the SKYGGN study. Patients were eligible for enrollment if they had an anterior chamber cell score ≥ 2 at their first postoperative visit 18 to 30 hours post-uncomplicated cataract surgery and a pin-hole ETDRS visual acuity without any other correction that was >20 letters (approximately 20/400) in the operative eye and >35 letters (approximately 20/200) in the fellow eye. Follow-up visits were scheduled at postoperative days 4, 8, 15, and 22.

The three study groups were similar at baseline in their demographic characteristics, and 148 patients completed the study. Mean age of patients across the three groups ranged from 66 to 68 years, approximately two-thirds of subjects were female, and the vast majority were Caucasian.

The percentage of patients with absence of anterior chamber cells on day 15 in the OCS-01 once daily, OCS-01 twice daily, and vehicle groups was 51.0%, 66.7%, and 19.6%, respectively (

<.0001 for both OCS-01 groups versus vehicle). Absence of pain on day 4 was achieved by 72.5% of patients treated with OCS-01 once daily and 45.1% of controls (

<.005). In the OCS-01 twice-daily group, 62.7% of patients were pain-free on day 4 (

“Data on percentage of patients with absence of anterior chamber cells from earlier postoperative visits show a statistically significant difference favoring the once-daily OCS-01 group versus vehicle was achieved on day 8. The results for the pain assessment showed the proportion of patients who were pain-free increased in all groups as follow-up continued, but the difference was statistically significant between both OCS-01 groups and vehicle at days 8 and 15,” Donnenfeld said.

One patient in the vehicle group and one patient treated with OCS-01 twice daily withdrew from the study because of an adverse event. However, there were no significant ocular or systemic adverse events. Importantly, IOP ≥30 mm Hg was not observed in any patients at any follow-up visits nor did any patient have a ≥10 mm Hg increase from baseline IOP.

“The overall adverse event rate was higher in the vehicle group than in the OCS-01 groups, probably because the adverse events were procedure-related rather than treatment-related,” Donnenfeld said.

Donnenfeld noted that the potent activity, safety, and tolerability of OCS-01 observed in SKYGGN are consistent with results of another phase 2 trial investigating the novel steroid formulation as a treatment for diabetic macular edema. The latter study enrolled 144 patients and found a statistically significantly greater decrease in central macular thickness in patients treated with OCS-01 compared with vehicle-treated controls. There were no significant ocular adverse events in the OCS-01 group.

A vehicle-controlled phase 2 study investigating once- and twice-daily administration of a novel, preservative-free topical formulation of dexamethasone as treatment for pain and inflammation after cataract surgery met its primary endpoints.



Novel dexamethasone formulation shows efficacy and safety with once-daily use

Loteprednol etabonate ophthalmic gel 0.38% (Lotemax SM, Bausch + Lomb) is a new iteration of the 

 with a number of benefits for patients, said Marguerite B. McDonald, MD.

Approved by the FDA in February for the treatment of postoperative inflammation and pain following ocular surgery, 

 with proprietary submicron technology that improves drug dissolution and penetration to target ocular tissues-resulting in treatment benefit with the convenience of twice-daily dosing.

Like its predecessor, loteprednol etabonate ophthalmic gel 0.5% (Lotemax, Bausch + Lomb), the agent is a non-settling gel in which the active ingredient remains homogenously distributed, obviating the need for patients to shake the container vigorously prior to instillation.

The submicron loteprednol etabonate gel is also gentle to the ocular surface because it contains two demulcents and is preserved with a very low concentration of benzalkonium chloride (0.003%), said Dr. McDonald, clinical professor of ophthalmology, NYU School of Medicine, and in private practice, Ophthalmic Consultants of Long Island, Lynbrook, NY.

She described submicron loteprednol etabonate gel 0.38% as “a huge step forward” in topical corticosteroid therapy. “The new submicron formulation of loteprednol etabonate gel brings the benefit of twice-daily dosing for a molecule that has a 20-year history documenting its efficacy and safety,” she said.

The submicron-sized drug particles in loteprednol etabonate gel 0.38% have a median diameter of about 0.6 Î¼m. By comparison, loteprednol etabonate gel 0.5% contains micronized drug particles that are about 3 Î¼m in diameter.

Even though the new submicron formulation contains a lower concentration of loteprednol etabonate, it is effective with just twice-daily dosing because of its better drug dissolution and drug penetration characteristics compared with the 0.5% gel formulation, Dr. McDonald said.

The efficacy and safety of submicron loteprednol etabonate gel 0.38% for the treatment of postoperative inflammation and pain was investigated in a double-masked, vehicle-controlled randomized study that included 514 patients undergoing cataract surgery [Fong R, et al.

The proportions of patients with 1) resolution of anterior chamber cells and 2) no pain on postoperative day 8 were assessed as the primary outcome measures. Statistically significant differences favoring the BID and TID submicron loteprednol etabonate groups compared with vehicle were found in the analyses of both anterior chamber cell resolution (26.9% and 28.7% versus 9.3%) and absence of pain (73.7% and 73.1% versus 47.7%).

No safety concerns emerged in the submicron loteprednol etabonate treatment groups, and the treatment was well-tolerated.

Dr. McDonald is a consultant to Bausch + Lomb and other companies that market topical anti-inflammatory medications.

New loteprednol gel reduces drop burden for treatment of postoperative inflammation, pain

Author | Cheryl Guttman Krader, BS, Pharm

Articles

Preventing post-cataract surgery endophthalmitis

Novel dexamethasone formulation shows efficacy and safety with once-daily use

Submicron formula ‘step forward’ in steroid therapy

Intraoperative aberrometry offers pros, cons for IOL surgical decisions