Cheryl Guttman Krader, BS, Pharm

Cheryl Guttman Krader is a contributor to Dermatology Times, Ophthalmology Times, and Urology Times.

Results of a two-week phase III study demonstrated efficacy of loteprednol etabonate ophthalmic suspension 0.25% found the investigational treatment was well-tolerated and had a favorable safety profile. 

This article was reviewed by Elizabeth Yeu, MD


	
	Loteprednol etabonate (LE) ophthalmic suspension 0.25% (Eysuvis, Kala Pharmaceuticals) met its primary and key secondary endpoints in a third phase III clinical trial investigating the corticosteroid in a 

The LE 0.25% suspension is formulated with a proprietary mucus-penetrating particle drug delivery technology (AMPPLIFY) that improves bioavailability of the active ingredient at the target site. 

Topline results from the phase III study known as STRIDE III showed statistical superiority of LE 0.25% suspension (formerly known as KP-121) compared with vehicle for improving signs and symptoms of 

. In addition, the investigational corticosteroid was well-tolerated and had a favorable safety profile.
	
	

New techniques probed for managing dry eye disease 

Elizabeth Yeu, MD, an investigator in the LE 0.25% studies, is assistant professor of ophthalmology, Eastern Virginia Medical School, Norfolk, VA, and a partner, Virginia Eye Consultants, Norfolk, VA. 

“The results from STRIDE III showing benefit of LE 0.25% suspension for improving both signs and symptoms of 

are quite positive and replicate what was seen in STRIDE I and II,” Dr. Ueu said. “Collectively, these studies enrolled almost 3000 patients, making STRIDE the largest DED clinical trial program to date, and the results indicate that LE 0.25% suspension is a rapid-acting, safe, and effective anti-inflammatory therapy.”

Dr. Yeu added that if approved, LE 0.25% suspension will be an important therapeutic addition for the temporary relief of the signs and symptoms of 

“It is estimated that more than 17 million people in the US suffer from DED and 80% to 90% of those individuals experience flares for which a steroid can be appropriate treatment,” she said. “While eye care providers have used topical steroids to quiesce acute DED flares, we are always cautious about the potential for IOP elevations. It is noteworthy that no patients treated with LE 0.25% suspension in STRIDE III had an IOP increase >5 mmHg leading to IOP >21 mmHg.”

STRIDE III was a multicenter, double-masked study that randomly selected 901 patients 1:1 to treatment four times a day for two weeks with LE 0.25% or vehicle. 

Patients were eligible for study enrollment if they had a documented clinical diagnosis of DED in both eyes and were only randomized to treatment if they still met the study’s eligibility criteria after a two-week run-in period during which they used the investigational product’s vehicle four times a day. 
	
	

Lab tear tests aid reimbursements, clinical application of dry eye 

Using a 0 to 100 mm visual analog rating scale, patients were instructed to record Ocular Discomfort Severity (ODS) daily in a diary. Patients returned for follow-up visits on days eight and 15 after randomization for evaluations that included conjunctival hyperemia, corneal staining, and safety.

The primary endpoint looked at change in ODS score at day 15 in the overall intent-to-treat (ITT) population and in the subgroup of ITT patients with more severe baseline discomfort (ODS ≥ 68 mm). 

STRIDE III achieved both of its independent primary endpoints, demonstrating a statistically significant difference in the LE 0.25% group compared to vehicle in the overall ITT population (

 = .0002) and the subgroup (n = 602) with more severe baseline ocular discomfort (

In analyses of secondary endpoints, LE 0.25% suspension demonstrated statistical superiority for improving conjunctival hyperemia at day 15 (

=.0282), and total corneal staining at day 15 (

Instillation site pain was the most common adverse event in both the LE 0.25% suspension and vehicle groups (2.9% and 1.5%, respectively). No patients in either group experienced an IOP increase >5 mmHg that resulted in an IOP ≥21 mmHg nor did any patient have an IOP increase >10 mmHg.
	
	


	In STRIDE I, LE 0.25% suspension achieved the sign and symptom endpoints and demonstrated rapid and sustained improvement in the ODS score.  In STRIDE II, LE 0.25%  suspension achieved its sign endpoint and showed a significant benefit for reducing corneal staining and for improving the ODS score at day eight.

Kala Pharmaceuticals is working on finalizing resubmission of the NDA for LE 0.25% suspension as a treatment for the temporary relief of the signs and symptoms of DED utilizing a two-week course of therapy. 
	
	

Dr. Yeu is a consultant to and investigator for Kala Pharmaceuticals and is a consultant to and does research for other companies that market or are developing products for the treatment of dry eye.

Articles

Investigational topical corticosteroid demonstrates efficacy for dry eye 

The AcrySof IQ PanOptix trifocal IOL delivers a full range of good uncorrected vision, leads to high rates of patient satisfaction, and simplifies surgical counseling and planning. 

This article was reviewed by Cathleen M. McCabe, MD

In August, the FDA granted approval for Alcon to market the AcrySof IQ PanOptix trifocal IOL. Surgeons who are using the lens, which is available in spherical and toric versions, agree that it is an important advance in presbyopia-correcting technology.

Cathleen M. McCabe, MD, chief medical officer, Eye Health America, and medical director, The Eye Associates, Bradenton, FL, said she began using the PanOptix IOL as soon as it became available and estimates that she had already implanted it in several hundred eyes within the first six months. 

“I think PanOptix is the lens we have been waiting for in the United States,” she said. “With the PanOptix, we can actually meet patient expectations for independence from glasses at all distances.”

Dr. McCabe noted that the patients she has implanted with the PanOptix have been very enthusiastic about their outcomes, and they are sharing their experience with family and friends. 
	
	

 Changing focus of accommodating IOLs now reaching a new level

“Happy and satisfied patients build the market and practices too,” she said. “Although the PanOptix has been available for a relatively short time, I am already seeing patients asking for it through word-of-mouth referral.”

In Canada, ophthalmologists have had access to the PanOptix IOL for more than three years. 

Rosa Braga-Mele, MD, MEd, professor of ophthalmology, University of Toronto, Toronto, Ontario, Canada, has been using the lens since it came onto the market in her country and echoed the idea that the lens has benefits for patients and practices.

“Unless we did some mixing and matching or mini-monovision, traditional multifocal 

 and extended depth of focus (EDOF) IOLs had a weakness at some focal point,” Dr. Braga-Mele said. “In contrast, the PanOptix IOL delivers a blended range of vision with good vision at distance, intermediate, and near without glasses.”

Dr. Braga-Mele noted that with the toric version, ophthalmologists can correct a good range of astigmatism.

“Appropriate patient selection and education are still critical, but given that is done, patients are very, very satisfied with their outcome,” she said. “Happy patients are a source for more patient referrals.”
	
	

Performance of trifocal toric IOL highlight in tests 


	Dr. Braga-Mele said that the PanOptix has become her go-to lens for patients wanting presbyopia correction. It is her lens of choice for patients who in the past she would have offered a bifocal multifocal IOL or an EDOF IOL, and she is offering the PanOptix to a broader pool of patients because of its superior range of vision.

Dr. McCabe pointed out that she has years of experience with various multifocal and accommodating presbyopia-correcting lenses, dating back to the days of the ReZoom and first ReSTOR IOLs. 

“I have always tried to find the best solution to match each patient’s needs with the fewest side effects,” she said. “PanOptix is the first lens that gives a useable, functional range of vision.”

With the PanOptix IOL, preoperative counseling conversations with patients have changed for the better. Dr. McCabe observed that in the past she spent a lot of time explaining a variety of options to patients.

“I used to have to say that I could provide technology that would give good uncorrected vision at distance and intermediate and functional vision for near,” she said. “Or, I could offer better near vision with excellent distance vision and ‘okay’ intermediate vision.”
	
	

Light-adjustable IOL technology creates novel treatment window 

As a third choice, Dr. McCabe said she could try to mix and match technologies to achieve a full range of uncorrected vision.

“It’s a different situation now that I can use one lens that predictably gives excellent vision at distance, intermediate, and near,” she said. 

Dr. McCabe also pointed out that in her discussion, she no longer has to distinguish between the intermediate and near focal points or offer surgery with different lenses in fellow eyes. 

“I tell patients that I have a lens that will allow them to see up close without glasses and that gives them independence from glasses for their distance vision too,” she noted. 

Surgical planning is also easier with the PanOptix because it eliminates mixing and matching and adjusting refractive targets. Both Dr. Braga-Mele and Dr. McCabe say they plan for emmetropia bilaterally when using the PanOptix IOL.
	
	

Advanced toric IOL improves refractive outcomes


	Dr. McCabe tells patients that 99% of patients in the FDA trial were so satisfied after surgery with the PanOptix IOL that they would want the same lens implanted again. In her practice, the few exceptions involve cases with a small refractive miss, and those can be solved with a touchup procedure.

“We have excellent technology for accurate biometry and advanced formulas for IOL power calculation, including for toricity. Refractive predictability with the PanOptix IOL has been excellent overall,” she said. 

Dr. Braga-Mele also observed that the refractive outcomes with the PanOptix IOL are predictable. She attributed its performance, in part, to the fact that it is built on the tried-and-true AcrySof IQ platform. 
	
	

Accurate data key for planning toric IOL surgery 

Although Dr. Braga-Mele said that is almost consistently achieving her target of emmetropia, vision outcomes with the PanOptix IOL seem to have some tolerance to residual sphere and cylinder. 

There are some conditions that can impact the results of the

“Patients seem to do well with this lens if they have up to 0.5 D of hyperopia or myopia and up to 0.6 D of astigmatism,” she observed.
	 


	Because the PanOptix IOL is diffractive technology, some patients can still experience dysphotopsias. 

Dr. McCabe says she explains that because the lens has a target-like design, some patients see rings around point sources of light following surgery. She goes on to say that the symptoms are relatively common early after surgery, but by six months, most patients are not bothered by them if they notice them at all. 

“I acknowledge that a very small percentage of patients still consider this issue a problem,” Dr. McCabe pointed out. “Then, patients can decide for themselves if this is a potential compromise they are willing to accept for the benefit of having great vision at distance and near.”

Dr. Braga-Mele said that she also discusses dysphotopsias with patients, but that the PanOptix IOL seems to be associated with a little better profile than bifocal lenses when it comes to halo and glare. 
	
	

Physicians on quest to end dysphotopsias in premium IOLs

Because it splits light to different foci, reduced contrast sensitivity is another issue to consider. Consequently, Dr. Braga-Mele and Dr. McCabe exclude patients as candidates for the lens if they have glaucoma or macular pathology affecting vision now or if there is a real risk for progression.

“If a patient has early diabetic retinopathy, age-related macular degeneration, or glaucoma, I consider the potential for it to worsen over time and reach a level where I think this technology would not have been the best choice,” Dr. McCabe explained. “In that setting, I would not implant the PanOptix IOL or any diffractive presbyopia-correcting lens.”
	 


	Dr. Braga-Mele and McCabe both emphasized the importance of identifying preexisting 

“Like all multifocal IOLs, outcomes with the PanOptix are sensitive to the condition of the ocular surface,” Dr McCabe said. “I look carefully for dry eye and treat it preoperatively because dry eye affects the accuracy of surgical planning as well as quality of vision.”

SHE added that some patients may need additional encouragement and more intensive education postoperatively to maintain management for 

so that the quality of their vision is good. 
	
	

Dr. McCabe explained that when patients express some dissatisfaction postoperatively, which is rare, she has found it helpful to ask if they notice fluctuation of their vision and if it seems better sometimes during the day than others. 

“If patients report fluctuating vision, I use the information to help them understand why a healthy ocular surface is important for good quality vision,” she said.

Dr. McCabe also noted that she explains that the only thing that fluctuates during the day is the condition of their ocular surface. 

“Their observation about fluctuation helps me understand their complaint about their vision and is a sign that if they follow the recommendations for treating their dry eye, their vision will stabilize at its better level,” she said. 

Beyond dry eye, Dr. McCabe and Dr. Braga-Mele look for other ocular surface conditions/corneal pathology and determine whether they can be adequately treated preoperatively or are a reason for not recommending any multifocal 

Dr. Braga-Mele is a consultant to Alcon and Johnson & Johnson Surgical Vision.

Dr. McCabe is a consultant to Alcon, Bausch +  Lomb, Johnson & Johnson Surgical Vision, and Carl Zeiss Meditec.

Trifocal IOL a key for premium cataract surgery practice 

Strategies lead to positive outcomes in tough cases

This article was reviewed by Ken K. Nischal, MD


	
	Findings from studies investigating the efficacy and safety of corneal collagen crosslinking (CXL) for keratoconus in pediatric-age patients and developmentally delayed adults and the consequences of leaving their ocular disease untreated provide a solid base of evidence for offering CXL to these populations, according to Ken K. Nischal, MD.

“In the United States, CXL is only approved for the treatment of progressive keratoconus in patients from 14 to 65 years of age, and so it may not be offered to younger children even if indicated,” said Dr. Nischal, professor of ophthalmology and chief, Division of Pediatric Ophthalmology and Strabismus, University of Pittsburgh Medical Center, Pittsburgh, PA. 
	
	

Corneal collagen crosslinking imperative in paediatric keratoconus 

Keratoconous is not uncommon, with incidence rates reported up to 265 per 100,000 patients. 

Unfortunately, disease onset tends to be in early adolescence, and these younger patients are at risk for rapid progression and a lifelong visual disability. 

Dr. Nischal said his take on the issue is that technology should be for those who cannot advocate for themselves or who are the most vulnerable. 

“Those individuals are the children and developmentally delayed adults,” he said, “In fact, there is mounting evidence that CXL should be offered to children at presentation rather than waiting for progression.”
	
	

Keys to assessing true crosslinking outcomes 


	Several published studies demonstrate that keratoconus progresses at a rate that is much faster in children than in adults and that CXL arrests disease progression in pediatric patients, said Dr. Nischal. 

Discussing some of these papers, he cited a study by Chatzis and Hafezi that reported a progression rate of 88% after one year of follow-up in a series of 59 eyes of 42 children awaiting CXL for keratoconus.

Another study by Leon-Mesplie et al. showed that children who did not have CXL for keratoconus had a sevenfold increased risk of requiring a keratoplasty compared to adults.

“If you do not want to do CXL in a child, you certainly do not want to have to perform penetrating keratoplasty considering the extra problems that it brings in terms of operative and postoperative issues,” Dr. Nischal said.
	
	

Estimating total corneal power key in keratoconus patients 

Other papers in the peer-reviewed literature show the safety and benefit of CXL for keratoconus in pediatric patients. In what is the largest published study to date, Padmanabhan et al. analyzed data from 194 eyes of 153 children ages 8 to 18 years old that underwent CXL for documented progressive keratoconus.

Of the 194 eyes, 142 had CXL using the standard Dresden protocol and 52 were treated using hypoosmolar riboflavin.

The CXL was associated with keratometric flattening and stabilization of pachymetry during follow-up extending to 6.7 years. Of the total cohort, 59 eyes were followed for longer than 4 years, and reversal of keratometric flattening occurred in 14 (24%) of those eyes. 

“Interestingly, however, the flattening did not correlate with significant changes in vision or corneal pachymetry,” Dr. Nischal said.

Findings from a study by Mazzotta et al. suggest that regression after CXL may be more likely in patients with severe allergy who are eye rubbers.

 These investigators reported outcomes for 62 eyes of 47 patients ages 8 to 18 years who underwent CXL and represents the report with the longest post CXL follow-up for a pediatric population. 
	
	

Traversing the CXL pathway: Where do we go from here?

The outcomes were stable at 10 years in 80% of eyes. A 2 D increase in mean keratometry occurred in four eyes of two patients who had severe ocular allergy and were eye rubbers, but stability was achieved after repeat CXL. No other patients in the series needed a repeat treatment because of CXL failure.

Two papers have reported on performing CXL for keratoconus in developmentally delayed patients.

Dr. Nischal noted that the patients, who often have Down syndrome, already have challenges. 

“Not performing CXL and therefore leaving them to possibly develop hydrops from progressive corneal thinning and lose vision makes their lives and the lives of their families much worse,” he said.
	
	

Doing justice to corneal irregularities 


	Reluctance to perform CXL in children and developmentally delayed adults may be partly due to concern that they will not remain still during a procedure performed using local anesthesia. In addition, children and developmentally delayed adults may not comply with instructions to avoid eye rubbing that not only increases the risk of regression over time but also the chance for infection following the procedure. 

To overcome these problems, Dr. Nischal said that he performs CXL in most pediatric patients and developmentally delayed adults under general anesthesia with a regimen that will result in complete paralysis.

“If there is not complete paralysis, the eye may roll up during the UV light application, leaving me grabbing for forceps to try to hold the eye in place,” he said.

Dr. Nischal said he uses integrated intraoperative OCT (Carl Zeiss Meditec) to assess adequacy of the riboflavin soak. 

An OCT scan prior to the soak allows for baseline evaluation and after the soak there is a visible change in reflectivity on the OCT. The OCT is also used after UV exposure. 
	
	

OCT providing physicians with improved view of ocular surface 

“If I see a clear interface after the UV light application, I know I am going to get a good result, but I do not yet have enough follow-up to know what the outcome is in cases where I cannot see the interface,” he said.

To protect the eye in the early post-treatment period while the epithelial defect is healing, he usually places a temporary central tarsorrhaphy for two days and prescribes topical moxifloxacin six times daily to be applied at the medial canthus. 

“So far, we have not had any cases of infection, and the children seem comfortable with the tarsorrhaphy in place,” Dr. Nischal said.
	
	

Study focuses on HOA measurements in normal keratoconic eyes 

Patients who had CXL elsewhere with placement of a bandage contact lens reported much less pain and discomfort with their second eye procedure using tarsorrhaphy. 

One case involved a developmentally delayed patient whose parents were very frightened about the child tolerating the second eye procedure. 

“The parents reported that with the lids sutured shut, the child did not touch the eye and was very relaxed,” Dr. Nischal said. 

Dr. Nischal is aggressive with treatment for allergic conjunctivitis-related inflammation both pre- and post CXL as a strategy to mitigate eye rubbing. Patients are also referred for behavioral therapy to reduce eye rubbing.
	
	

CXL-LASIK pairing can enhance refractive outcomes 


	Between July 2018 and September 2019, Dr. Nischal performed CXL in 18 eyes of pediatric patients. All cases were done using the standard Dresden protocol. 

Sixteen cases were done using general anesthesia, of which 14 had a temporary tarsorrhaphy placed and two had a bandage contact lens. Eight of the cases involving temporary tarsorrhaphy were in developmentally delayed or non-verbal children. 

Topical anesthesia with post-CXL placement of a bandage contact lens was used in two eyes of healthy teenagers aged 15 years. 

This article is based on a presentation given by Dr. Nischal at the American Academy of Ophthalmology's 2019 annual meeting. He has written an editorial on this topic (Reference #7). Dr. Nischal receives honorarium from Carl Zeiss Meditec, but has no other relevant financial interests to report. 

1. Chatzis N, Hafezi F. Progression of keratoconus and efficacy of pediatric corneal collagen cross-inking in children and adolescents. 

2. Leoni-Mesplie S, Mortemousque B, Touboul D, et al. Scalability and severity of keratoconus in children. 

3. Padmanabhan P, Rachapalle Reddi S, Rajagopal R, et al. Corneal colleagen cross-linking for keratoconus in pediatric patients: log-term results. 

4. Mazzotta C, Traversi C, Baiocchi S, et al. Corneal collagen cross-linking with riboflavin and ultraviolet a light for pediatric keratoconus: ten-year results. 

5. Koppen C, Leysen I.  Riboflavin/UVA cross-linking for keratoconus in Down syndrome. 

6. S abti S, Tappeiner C, Frueh BE. Corneal cross-linking in a 4-year-old child with keratoconus and down syndrome. 

7. Lalgudi VG, Nischal KK. Pediatric corneal collagen cross-linking for keratoconus: not an experimental procedure.

CXL imperative in treatment of pediatric keratoconus 

Cataract surgeons appear to have growing confidence using presbyopia-correcting IOLs in patients with a history of keratorefractive surgery. 

This article was reviewed by Arthur B. Cummings, MD


	
	Though a history of keratorefractive surgery has generally been considered a contraindication to implantation of a presbyopia-correcting 

, the landscape appears to be changing, according to findings of a survey of surgeons.

According to Arthur B. Cummings, MD, consultant eye surgeon and medical director, Wellington Eye Clinic, Dublin, Ireland, patients who have previously undergone keratorefractive procedures and enjoyed the benefits of good vision demand similar results after

 can unmask aberrations that can be present in the

or caused by an abnormal tear film, putting these patients at risk for reduced quality of vision,” he added. 
	
	

Dr. Cummings sought to identify current practices for using presbyopia-correcting 

 in patients with a history of keratorefractive surgery by sending a survey to almost 150 colleagues regarded as experts in both keratorefractive and 

. Ninety surgeons replied, and their responses showed that approximately two-thirds were using presbyopia-correcting IOLs in this challenging population, and the majority of those users were satisfied with the outcomes.

Additional data collected in the survey indicated that greater use of presbyopia-correcting 

 in patients with a history of keratorefractive surgery was supported in part by the availability of new IOL technology and surgeon confidence gained from careful patient selection. 

“When considering whether or not a patient is a good candidate for a presbyopia-correcting 

l optics (i.e., higher order aberrations) and the state of the corneal surface were key,” Dr. Cummings said. “Patient personality, realistic expectations, and motivation also came forth as important issues.”
	
	

 Presbyopia-correcting IOLs: Expanding, improving last frontier 

Among the surgeons who were not using presbyopia-correcting

 in patients with a history of keratorefractive surgery, poor past experience was the leading reason. Comments, however, brought forth the importance of considering each case individually with particular attention to 

 optics, the condition of the ocular surface, and patient personality.

According to Dr. Cummings, opinions were mixed on whether better outcomes could be achieved in patients who had undergone keratorefractive surgery for myopia versus hyperopia.
	
	The level of correction was considered when deciding to use a presbyopia-correcting 

 in hyperopes-patients with a lower amount of hyperopia were generally preferred-whereas patients who had high myopia were not more likely to be excluded than their counterparts with low to moderate myopia. 

 Doing justice to corneal irregularities 


	Given a list of IOL design types, the surgeons’ responses indicated that their most satisfactory results overall were achieved using the pinhole optic IOL (IC-8, AcuFocus) followed by trifocal lenses. 

“The survey responses indicated that good results could be achieved with all presbyopia-correcting IOL designs,” Dr. Cummings noted. 

Corresponding with the preference for the pinhole optic 

, data from the Australian IC-8 IOL SHARE study showed that the IC-8 IOL was chosen more often than all other presbyopia-correcting IOLs combined in eyes with irregular 

“The IC-8 accounted for more than half of the presbyopia-correcting lenses implanted in eyes with irregular 

, but it was also used in 20% of all normal eyes receiving a presbyopia-correcting IOL,” Dr. Cummings concluded. 
	
	

Read more by Cheryl Guttman Krader, BS, Pharm

Author | Cheryl Guttman Krader, BS, Pharm

Articles

Investigational topical corticosteroid demonstrates efficacy for dry eye

Trifocal IOL a key for premium cataract surgery practice

CXL imperative in treatment of pediatric keratoconus

Finding an option with presbyopia-correcting IOLs