Cheryl Guttman Krader, BS, Pharm

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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.

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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.

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

Intraoperative aberrometry offers pros, cons for IOL surgical decisions

	Reviewed by Damien Gatinel, MD, and Nick Mamalis, MD

	For patients seeking spectacle independence after cataract surgery or refractive lens exchange, implantation of a trifocal IOL is a better option than a lens with a bifocal optic or an extended depth of focus/extended range of vision design, according to Damien Gatinel, MD.

	Whether using a bifocal or trifocal IOL, however, there are certain issues surgeons should consider in order to optimize outcomes and the likelihood of achieving satisfied patients, said Nick Mamalis, MD.

	Reviewing the attributes of the different multifocal IOLs, Dr. Gatinel explained that relative to bifocal and extended depth of focus/extended range of vision designs, trifocal IOLs provide a more continuous range of uncorrected vision.

	Furthermore, available evidence indicates trifocal IOLs deliver their benefit without increasing the risk of unwanted visual phenomenon.

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	“A bifocal IOL can provide good uncorrected vision at far and at near distances that are in the range of 30 to 45 cm, but they do not give good uncorrected vision for intermediate vision, which is important today for people who are working at a desktop computer, using a laptop, or reading a tablet,” explained Dr. Gatinel, assistant professor of ophthalmology, and head, anterior segment and refractive surgery department, Rothschild Ophthalmology Foundation, Paris.

	Even lowering the add power of a bifocal IOL does not result in good intermediate vision because a “confusion focus” remains between the near and distance foci, he noted.

	“Extended depth of focus and extended range of vision IOLs afford better intermediate vision than a bifocal IOL,” Dr. Gatinel said. “With these newer technologies, however, patients may still need to wear glasses for some near vision tasks.”

	Dr. Gatinel was involved in the design of the first trifocal IOL that became commercially available (FineVision, PhysIOL) in Europe in March 2010.

	“The idea for this implant was born in my mind when I realized patients who were implanted with a bifocal IOL would thank me for their ability to read and drive without glasses, but they noted they still needed glasses with a low add for working at the computer,” he said.

	In order to improve vision at intermediate distances, Dr. Gatinel designed an implant combining two bifocal designs-one for distance and near and other for distance and intermediate.

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	In addition, the optic incorporates apodization and step heights that maintain good distance vision. The lens is also pupil dependent so that contrast at distance is increased with the pupil is large and vice versa.

Currently, two other trifocal IOLs are also available in Europe, of which one features an optic design similar to that of the FineVision IOL (AT Lisa Tri 839mp, Carl Zeiss Meditec) while the other combines two diffractive gratings with a nonharmonic relation (Panoptix, Alcon Laboratories).

	Dr. Gatinel noted that results of optical bench testing assessing the trifocal IOLs demonstrate their benefit for providing better intermediate vision compared with a bifocal IOL. Defocus curve findings in a French multicenter study evaluating patients implanted with the FineVision trifocal IOL are consistent with the optical bench results in showing that the trifocal design provides a continuous range of clinically useful visual acuity.

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	“The defocus curve shows more of a plateau rather than a trough between the distance and near visual acuities,” he said.

	Data on visual quality measures and symptoms show that while contrast sensitivity is reduced with both bifocal and trifocal technology relative to monofocal IOLs, it is similar at near and distance comparing the two presbyopia-correcting technologies and better at intermediate with the trifocal IOL.

	The potential for halos and starburst with trifocal IOLs has also been extensively studied and found to be similar to or less than that associated with bifocal technology, Dr. Gatinel said.

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	“Our experience in clinical practice is that patients implanted with a trifocal IOL may mention they see halos,” he said. “However, these patients usually do not complain about visual symptoms and the number of individuals who say they cannot drive at night because of bothersome symptoms is very low.”

	Nevertheless, surgeons implanting a trifocal IOL should warn patients about the potential for postoperative halos and glare, he noted.

	Because trifocal IOLs are only available in countries outside of the United States, Dr. Mamalis noted that he lacks first-hand experience with these implants.

	However, the considerations for achieving success with trifocal IOL implantation are similar in many respects to those pertaining to bifocal IOLs, said Dr. Mamalis, professor of ophthalmology, John A. Moran Eye Center, University of Utah, Salt Lake City.

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	In summary, he advised surgeons to choose patients carefully and counsel them thoroughly so that they have realistic expectations regarding visual outcomes.

	In addition, he emphasized the importance of obtaining accurate preoperative measurements, minimizing residual refractive error, and achieving good IOL centration.

	If faced with a patient who is dissatisfied postoperatively, surgeons should try to identify and address potentially correctable problems.

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	“Ultimately, however, if you cannot make the patient happy, consider exchanging the multifocal IOL for a monofocal lens,” Dr. Mamalis said.

	Implantation of multifocal IOLs should be approached with caution in people with certain personality types, professions, or vision needs, as these individuals may not tolerate the trade-offs inherent in multifocal optic technology, Dr. Mamalis suggested.

	“People with type 1 personalities, anyone who is obsessive-compulsive, as well as lawyers, engineers, and people who do extensive night driving or working in dim-light conditions may be unhappy with the limitations of these IOLs, which include reduction in contrast and night-time visual symptoms,” he said.

	“That is not to say use of these lenses is absolutely contraindicated for these individuals,” Dr. Mamalis said. “Before proceeding to implant these lenses, however, surgeons would do well to think twice and counsel these patients thoroughly about the potential downsides.” 

	A comprehensive ocular examination is also critical because patients who undergo multifocal IOL implantation should have healthy eyes free of any sight-threatening pathology. Careful attention should be given to the condition of the ocular surface.

	Dr. Mamalis recommended avoiding implantation in anyone with corneal scars or dystrophies and in patients with dry eye whose tear film abnormalities cannot be corrected through preoperative treatment.

	“These patients will not do well because vision is degraded by tear film abnormalities and potentially will be further degraded by the lens,” he said.

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	Macular pathology should also be identified preoperatively because it too degrades image quality, and so surgeons may consider performing OCT to identify abnormalities that otherwise may not be visible through the cataractous lens.

	“Age-related macular degeneration and epiretinal membranes are relatively common in the population of older patients undergoing cataract surgery,” Dr. Mamalis said. “Epiretinal membrane can be treated preoperatively, but it first has to be detected, and that may be challenging looking through an opacified lens.”

	He suggested that patients who have mild glaucoma that is well-controlled remain reasonable candidates for a multifocal IOL. However, Dr. Mamalis advised exerting greater caution in anyone with more advanced glaucoma.

	Patient satisfaction after multifocal IOL surgery also depends on achieving good refractive outcomes, and so accurate biometry is critical as is astigmatic management. Dr. Mamalis noted that residual astigmatism exceeding 0.5 D or 0.75 D will considerably degrade image quality.

	“Be careful to control your ametropic and astigmatic results when putting in a bifocal or trifocal IOL,” he said.

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	Proper lens centration is also critical for optimizing postoperative visual quality with multifocal IOL technology.

	“Any significant decentration of the implant will result in a dramatic drop in quality of vision,” he said. “For that reason, if there are any complications intraoperatively that can affect lens centration and stability consider converting to a monofocal IOL.”

	Information from studies that have investigated reasons for multifocal IOL explanation and patient dissatisfaction with multifocal IOLs reinforces the advice offered by Dr. Mamalis.

	Data from an annually conducted ASCRS/ESCRS survey show that unwanted visual phenomenon, e.g., glare and optical aberrations, are the most common reasons for multifocal IOL explanation, followed by problems with dislocation and decentration.

	The most common reasons for patient dissatisfaction are blurred vision with or without photic phenomenon and photic phenomenon in general, and the common etiologies underlying these complaints are residual ametropia and astigmatism, posterior capsule opacification (PCO), and large pupil size.

	“These are all issues that interact with optical performance and accentuate potential problems with multifocal IOL technology,” Dr. Mamalis said.

	Findings of other studies were similar in showing reasons for multifocal explanation or patient dissatisfaction included decreased contrast sensitivity, photic phenomena, blurred vision, anisometropia, and dislocation/decentration, as well as incorrect IOL power and excessive preoperative patient expectations.

	“These data again underscore the need to counsel patients carefully about the outcomes and to beware of those who seem to want magic and are hoping for complete spectacle independence,” Dr. Mamalis said.

	Although vision problems that are secondary to PCO can be addressed by Nd:YAG laser capsulotomy, Dr. Mamalis cautioned that if the patient remains unhappy after the procedure, lens explantation will be more challenging in the setting of an open capsule.

	“Before performing capsulotomy, make sure first that the problem is caused by the PCO and not something else,” he said.

	This article is based on presentations given by Dr. Gatinel and Dr. Mamalis during the 2015 meeting of the American Academy of Ophthalmology. Dr. Gatinel is a consultant to PhysIOL and holds a patent and proprietary interest in the FineVision trifocal IOL.

	Dr. Mamalis is a consultant/advisor for companies that market IOLs.

Multifocal IOLs offer the potential to reduce spectacle dependence, but outcomes vary depending on optical design. Optimizing success and satisfaction depends on careful patient selection, thorough counseling, and good surgical technique.

Achieving patient satisfaction with multifocal IOLs

-Findings from a retrospective study of patients undergoing corneal collagen crosslinking (CXL) for keratoconus provide new insight on the risk of early ocular surface related complications.

The study included 206 eyes of 180 patients with keratoconus and found 23 eyes (11.2%) of 22 patients presented with 28 marked ocular surface complications. The research was conducted by Denise Wajnsztajn, MD, Joseph Frucht-Pery, MD, and colleagues from the Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, who extracted data on clinical features and early adverse events/complications of patients who underwent CXL between August 2007 and March 2012.

Compared with the 183 eyes that did not develop an early complication, the complication group was similar with respect to age and gender. However, they presented with more advanced keratoconus as evidenced by a significantly steeper mean K

 and significantly thinner mean pachymetry.

In addition, features leading to ocular surface compromise were prominent in the complication group prior to CXL. Ocular surface and external disorders were common, half of the patients were contact lens-dependent, and 17% had limited tolerance to contact lenses.

Best-corrected visual acuity (BCVA) loss of 1 to 3 lines compared with the pre-CXL level occurred in 6 eyes.

“Long-term complications of CXL, including scarring and loss of BCVA, have been well described,” said Dr. Wajnsztajn, second-year corneal fellow. “However, there is insufficient information on the early complications that can occur

 “Our data show that compromised ocular surface healing after CXL may be more common than recognized and that it can compromise final visual acuity,” Dr. Wajnsztajn added. “This information indicates that eyes should be in the best ocular surface condition before undergoing CXL in order to achieve the best outcomes.”

The patients in the study had been treated over a period of about 4.5 years beginning in August 2007. All of the CXL procedures were performed using the Dresden protocol.

Findings prior to CXL in the eyes that developed early ocular surface complications included floppy eyelids in more than half, mild superficial punctate keratitis in almost half, and allergic conjunctivitis in 13%

 The most common complications represented epithelial healing failure (19 eyes) followed by corneal infiltrates (8 eyes), of which two were associated with a positive microbial culture. In addition, one eye developed severe stromal edema that lasted for more than 1 month and led to subsequent scarring.

“The findings in this eye led us to question the development of corneal hydrops as a result of CXL,” Dr. Wajnsztajn said.

No eye went on to develop corneal melt or perforation.

Dr. Wajnsztajn proposed a model to explain the risk of early ocular surface complications after CXL treatment for keratoconus

 “These patients may suffer from chronic inflammation associated with prolonged contact lens wear and exposure to cleaning solutions, chronic allergies, blepharitis, eye rubbing, and floppy eyelids that can lead to dry eye, corneal hyposensitivity, and compromised ocular surface healing after CXL,” Dr. Wajnsztajn said.

Dr. Wajnsztajn has no financial interest in the subject matter.

A study provides new insight on the risk of early ocular surface-related complications among patients undergoing CXL for keratoconus.

Author | Cheryl Guttman Krader, BS, Pharm

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