Introduction
At the 2024 ASCRS meeting in Boston, esteemed colleagues and I hosted the first ever panel discussion on LACRIFILL Canalicular Gel (Nordic Pharma, Inc.), a cross-linked hyaluronic acid gel for the treatment of dry eye disease (DED). In this abbreviated version of that discussion, we explore this novel approach to treating dry eye. Read on for background on DED and lacrimal occlusion; the exciting application of cross-linked hyaluronic acid as a lacrimal filler; the results from the LACRIFILL clinical trial; and coding and billing implications for incorporating LACRIFILL into clinical practice.
— Mark Packer, MD, CPI
Lacrimal Occlusion: A Key to Treating Dry Eye Disease
Preeya K. Gupta, MD
DED is a very common condition, with prevalence estimates for people older than 50 at approximately 7.8% among women and just over half of that for men.1 Every day, we surgeons see the negative impact DED has on patients’ vision-related quality of life. Affected patients aren’t going blind, but they feel like they’re losing their vision.
We know that the central mechanism of dry eye is hyperosmolarity, which leads to tear film instability and a cascade of inflammation.2 Many factors contribute to this condition. Patients can have excessive evaporation, or they can poorly produce aqueous, or both. According to the Tear Film & Ocular Surface Society's (TFOS) DEWS II Report Executive Summary, patients can present symptomatically or asymptomatically,2 so it’s important to look for the presence of DED in both surgical patients and those who are coming in for routine exams. Chris Starr, MD, and I published a study 6 years ago in which we evaluated the ocular surface of approximately 120 patients coming into each of our clinics for cataract evaluation.3 We found that 80% of these patients had some level of dryness (an abnormal tear test or corneal staining). If you’re not diagnosing dry eye in cataract surgery candidates, you’re probably missing them.
Perioperative Patients
The American Society of Cataract and Refractive Surgery (ASCRS) Cornea Clinical Committee, which I was a part of, felt strongly that perioperative patients should be screened differently than even our general population of patients because dry eye is one of the most common reasons why patients are unhappy after cataract surgery. That is really the call to action. If we want to take advantage of these modern technologies at the time of cataract surgery, the perioperative patient must have a robust tear film. Corneal incisions, whether made during cataract surgery or laser vision correction, can worsen DED. A recent paper showed that higher-order aberrations increase over time in dry eye patients, whether it’s from aqueous deficiency or meibomian gland dysfunction (MGD).4
The ASCRS website has free, downloadable tools for identifying and treating ocular surface disease, including a preoperative diagnostic algorithm, a modified patient questionnaire that has some lifestyle questions, and also a SPEED Questionnaire (available at: https://ascrs.org/clinical-education/cornea/ascrs-preoperative-osd-algorithm).
Best-Practice Treatments for the Perioperative DED Patient
How we practitioners treat perioperative patients is broad and disparate; everyone does a little something different. These are not the patients I hand a bottle of artificial tears to—I feel strongly about treating them. Among the long list of possible treatments recommended in the TFOS DEWS II Report,2 I think punctal occlusion is one that is maybe a little underutilized as it relates to the perioperative patient. The American Academy of Ophthalmology, as part of its periodic ophthalmology assessments, looked at the safety and efficacy of lacrimal drainage system plugs for dry eye. They found that plugs improve the signs and symptoms of moderate dry eye that are not improved with topical lubrication. Plugs are generally well tolerated, and serious complications are infrequent. The report noted that, amongst all plug types, about 9% of the patients had epiphora, and 10% required removal because of irritation.5 I’ll ask the panel: how often do you remove plugs?
Panel Discussion
Darrell E. White, MD: It’s amazing how often we see scarring around the plug. Treating it involves not just removing the plug, but everything we have to do along with it to remove scar tissue. Sometimes, it’s a real honest-to-goodness skin surgery procedure.
Eric D. Donnenfeld, MD: I stopped using external plugs about 5 years ago. With lissamine green staining, you almost always see where the plug rubs against the conjunctiva and disturbs the mucin layer. It creates irritation. I only use collagen plugs right now, which also don’t work optimally. I remove older collagen plugs all the time, and they’re frequently coated with glycoprotein that’s completely infested with bacteria. It’s just not the best way of occluding a punctum.
Dr. Gupta: Absolutely. They’re not benign, for sure. I think one question that comes up for clinicians is whether punctal plugs will worsen an eye that already has inflammation. Louis Tong, MD, in Singapore, published a paper in 2018 in which he and colleagues measured tear cytokine levels in patients with punctal plugs, and they found that the cytokine levels were not altered by the insertion of plugs.6 We’re not making patients’ inflammation worse by taking the punctal occlusion approach.
External plugs are not benign, however. Clinicians have found epithelial defects, chafing, and irritation along the conjunctiva, etc., after plug insertion. If the goal of punctal plugs is to treat foreign-body sensation and irritative symptoms, then patients who experience negative reactions will likely not be pleased.
Another issue with punctal plugs can be retention. In a 2015 study, Brissette et al looked at punctal plug retention rates in patients with moderate-to-severe dry eye, and 68% of the Parasol punctum plugs (Sigma Pharmaceuticals) were retained, compared to 32% of Superflex punctum plugs (Katena).7 Sometimes plugs can migrate, and sometimes patients can get stones in their ducts. Also, the plugs can be a nidus for infection. I’ve had patients whom I’ve had to send to an oculoplastics physician to have a punctal plug flushed out and treated. Another thing to consider: mechanical stress and migration are not insignificant in this patient population; we clearly have an unmet need.
I think many of us really do believe in punctal and lacrimal occlusion as an important pathway for treating dry eye, but our wish list is to have something with high tolerability and efficacy—something that is easy for the patient and the clinician. I think LACRIFILL Canalicular Gel (Nordic Pharma, Inc.) is an exciting product that meets these criteria.
A New Approach to Lacrimal Occlusion: Cross-linked Hyaluronic Gel
Eric D. Donnenfeld, MD
Let me introduce a new, novel intracanalicular filler that I consider to be next-generation punctal occlusion. It is hyaluronic acid that has been cross-linked into a hardened state, which lets it stay in the tissue for longer periods of time (Figure 1). It is called LACRIFILL Canalicular Gel (Nordic Pharma, Inc.)
I do not use external-dwelling punctal plugs because they damage the conjunctiva, and they are niduses of infection that become coated in biofilm.8 I prefer an indwelling plug, although sizing them can be tricky because patients’ lacrimal drainage anatomy is variable. For these reasons, a form-fitting lacrimal filler makes sense. The ideal lacrimal occlusion device would be something that conforms to the anatomy of the canalicular system. It has to be comfortable, and it has to be inert so that it can’t be secondarily infected. And, it has to be removable if needed. That’s really what LACRIFILL is, a disruptive new technology that advances the field of dry eye. I’m a big believer in punctal plugs; I think that they are underutilized. To me, it’s a win-win to put a punctal plug in—it’s good for the patient and good for your practice.
LACRIFILL Material and Insertion
Cross-linked hyaluronic acid has been around for a long time. It’s very comfortable and well utilized. LACRIFILL is placed in the puncta via an inserter or cannula (Figure 2). The gel is soft but firm, and it adheres to the walls of the canalicular system so that it stays in place for long periods of time. Thus, its chemical and physical properties make it an ideal filler.
Inserting LACRIFILL is a comfortable procedure; there’s no need for more than a topical anesthetic. It’s so simple to implant that optometrists, ophthalmologists, or physician assistants can do it. And, it’s a great addition to your practice. It fills an unmet need, and it’s a wonderful revenue source.
LACRIFILL Clinical Trial Results
In a single-site, open-label, prospective study published in 2018, 74 participants with dry eye who were dissatisfied with artificial tears were fitted bilaterally with 0.2 mLs of the cross-linked hyaluronic acid in the lower canaliculus using a 23-gauge lacrimal irrigator.9 The patients were evaluated at baseline and at 1 and 3 months with a corneal slit-lamp examination, including fluorescein staining, Schirmer test, tear breakup time (TBUT), and tear meniscus height. The study concluded at 6 months with a telephone questionnaire, which 63 patients completed (mostly female, with a mean age of 67).
The results were a demonstrable reduction in corneal fluorescein staining. Schirmer scores showed an increase of 3.67 mm on average after 3 months (Figure 3), which was very significant. TBUT improved by 87% (Figure 4), and tear meniscus height increased by 57% at 3 months over baseline (Figure 5). The device was safe, with no significant side effects (there was 1 case of viral conjunctivitis that resolved at 2 months).
Whenever I evaluate a product, especially a product for dry eye, I look at three variables. The first is efficacy: Does it work? The second is rapidity of action: How long does it take before it works? The third is tolerability: Can the patient be comfortable with this? LACRIFILL checks the boxes on all three variables. It works immediately and is very well-tolerated, with essentially no side effects. This device is remarkably efficacious; the Schirmer scores almost doubled as a mean by 3 months, and TBUT and tear meniscus height both showed significant improvement in this patient cohort.
The investigators asked the patients to answer a telephone questionnaire about how their eyes felt at 6 months after LACRIFILL insertion. Out of 63 respondents, 63% reported that their eyes felt better; 57% said their eyes felt wetter; 94% stated they had had no post-implantation infections; and 83% said they had experienced no significant pain. These subjective responses coupled with the positive study results make LACRIFILL my punctal occlusion device of choice.
The LACRIFILL Pivotal Clinical Trial: The HaLF DOME Trial
Mark Packer, MD, CPI
I served as Chief Medical Officer for Visant Medical, the sponsor of the clinical trial that obtained 510(k) clearance for LACRIFILL Canalicular Gel (Nordic Pharma, Inc.). The study was a prospective, multicenter, randomized, controlled, double-masked clinical trial to evaluate the safety and effectiveness of cross-linked hyaluronic acid (HA) gel for lacrimal occlusion and improvement of the signs and symptoms of dry eye disease.10 In this study, 157 patients were randomized; 99 patients with bilateral cross-linked HA filler and 52 patients with bilateral hydrogel plugs completed the study. Subjects had at least moderate dry eye; they had to have a Schirmer score of ≤10 mm or less and a score on the Ocular Surface Disease Index (OSDI) of ≥23. Patients’ average age was mid-60s, and more often they were women. We excluded any subject who had an ocular condition that may have interfered with the interpretation of study results.
Patients’ baseline anesthetized Schirmer scores were below 10 mm or less. Our control was the only commercially available canalicular hydrogel plug, called FormFit (Oasis Medical).
The primary effectiveness endpoint was an improvement in Schirmer score at 3 months, and we also looked at the 6-month results (Figure 6).
Most interestingly, we saw no diminution of effect up to 6 months after LACRIFILL implantation, and patients’ improvement in Schirmer scores from baseline was really significant. Statistically, we saw a 63% increase (8.7 mm) of Schirmer scoring at 3 months, and an increase of 67% at 6 months (8.9 mm) compared to the mean baseline of 5.4 mm.
Our second primary endpoint was patients’ symptoms using the OSDI questionnaire, the scoring of which goes from zero (symptom-free) to 100 (incapacitating symptoms). Almost 84% of patients in both groups had significant improvement in symptoms (Figure 7). The LACRIFILL group showed an improvement from baseline (mean, 48.3) to 21.4 at 3 months (P < 0.0001) and 23.7 at 6 months (P < 0.0001). This was a tremendous improvement. Considering the OSDI score, 83.8% of the LACRIFILL patients showed a clinically meaningful improvement in symptoms out to 6 months, versus 84.6% of the Oasis hydrogel group.
We also looked at patients’ corneal fluorescein staining. Interestingly, the staining decreased from baseline to 3 months and then continued to decrease out to 6 months with LACRIFILL (Figure 8). In the Oasis hydrogel group, corneal staining started getting worse again at 6 months for reasons that are not entirely clear. This is one reason I prefer LACRIFILL.
Tear break-up time increased significantly in the LACRIFILL clinical trial, from a baseline of 3.0 secs to 3.8 secs at 3 months and 4.0 secs at 6 months (P < 0.0001). We also performed a dye disappearance test just to make sure that the LACRIFILL was still there. The immediate mean effect seen at week 1 stayed exactly the same out to 6 months, at which point the FDA told us to irrigate it out.
LACRIFILL: The Ideal Substance for Lacrimal Occlusion
The ideal canalicular occlusion device should be biocompatible, reversible, repeatable, safe, and have a low rate of complications. Synthetically cross-linked hyaluronic acid meets these criteria by creating a robust gel that resists degradation. This hydrogel is 98% water, yet its small particles stick together with enough force to remain intact. It is soft enough to conform to the delicate inner walls of the canaliculus, yet strong enough to block tear outflow.
LACRIFILL can be administered at the slit lamp or inserted using loupes as the patient reclines in the chair. Injecting LACRIFILL into the puncta is just like performing irrigation; I place the tip of a lacrimal cannula into the puncta and depress the plunger. I stop when I see the gel come back out through the opening. I like using a 27-gauge Bailey cannula. Because it has a tapered tip, I don’t have to dilate the patient most of the time.
The trial’s safety data were typical for lacrimal occlusion. There was a little bit of increased corneal staining in some patients: 7.8% in the LACRIFILL group and 16.7% in the OASIS group (NEI scale). As I mentioned, corneal staining on average continued to decrease with LACRIFILL through 3 and then 6 months, but in the Oasis group, it started to increase again.
Some patients, about 1 in 20, felt a little bit of discomfort during the insertion of the gel. When we asked the doctors to rate the patients’ pain on a scale from one to five, the average was approximately 1.2. Then, we asked the patients to rate their pain on a scale from 1 to 10, and the average was about 1.5.
LACRIFILL achieved 510(k) clearance and is available in the United States.
Adding LACRIFILL to Your Armamentarium
Darrell E. White, MD
Historically, we clinicians have approached dry eye in an “either/or” paradigm. We either treated these patients with steroids or with immunomodulators. We either plugged or we didn’t. We now know so much more about dry eye, and we’re now layering different treatments on top of one another. For us, as dry eye doctors and as cataract surgeons, LACRIFILL Canalicular Gel (Nordic Pharma, Inc.) can be the ultimate additional treatment or a standalone option. Alongside it, we can treat the ocular surface with whatever we think is necessary. We can use any type of anti-inflammatory medicine, either short-term or long-term, but we can also use an anti-evaporation medicine.
We all should be diagnosing ocular dryness perioperatively, and LACRIFILL is an ideal solution. It essentially pretreats any ocular surface dryness we may cause by other interventions. It’s biocompatible, long-lasting, and comfortable for patients. It’s both reversible and repeatable. If a patient’s relief starts to wane, there’s no reason why we can’t repeat the procedure.
Patient Profile
Who is going to benefit from LACRIFILL? The answer is any patient who has signs or symptoms of dry eye. Based on the clinical trial data, the ideal patient is one with an anesthetized Schirmer score of ≤10 mm, an OSDI score of ≥23, and mild-to-moderate corneal staining. In my opinion, however, this device should become a basic part of the blocking and tackling of treating dry eye in general. It’s ideal for the perioperative dry eye patient. Any anterior-segment procedure we perform will make a patient’s eye drier, and if we make someone symptomatic without mitigating it beforehand, it’s a problem.
Insertion
LACRIFILL is a simple, in-office procedure; I’ll perform it the same way that I do probing and irrigations. I’ll use loupes, and from a standing position, the implantation will take just a couple of seconds (Figure 9).
Preparing LACRIFILL is also quick and easy. You attach the cannula of your choice and make sure it's secure. Prime with 1/10 cc of LACRIFILL, and stop once you see gel at the tip. Inject 1/10 cc into the punctum and stop once you see reflux. Insert the cannula’s tip into the punctum in the same way you would use plugs. Most patients do not need all four of their puncta plugged. I suggest plugging the lower puncta to start.
I find LACRIFILL to be super versatile. It can be primary therapy when treating any dry eye patient with evidence of decreased tear volume, and I think it is ideally suited to the perioperative period. I predict that those surgeons who go out of their way to treat dryness are going to make LACRIFILL part of their routine protocols.
Dry Eye Disease, LACRIFILL, and Reimbursement
Kevin J. Corcoran, COE, CPC, CPMA, FNAO
Currently, there is no Local Coverage Determination (LCD) policy for LACRIFILL Canalicular Gel (Nordic Pharma, Inc.). In the absence of an LCD, we use Medicare’s reasonable and necessary criteria, which is national in scope and serves as the foundation for any coverage policy. This product meets all of those criteria.11 LACRIFILL is FDA-cleared, and it was found to be safe and efficacious in its clinical trial. In terms of duration and frequency, follow the accepted standards of ophthalmic medical practice as defined by the American Academy of Ophthalmology’s preferred practice pattern (PPP) for DED and the DEWS II report.2 It is administered in an in-office procedure, as are most punctal occlusion treatments for DED. It can be ordered and furnished by qualified personnel—ophthalmologists, optometrists, physician’s assistants, and nurse practitioners.
The Medical Necessity of Punctal Plugs
When used within accepted parameters of the PPP, LACRIFILL meets, but does not exceed, the patient’s medical need. Specifically, punctum or punctal plugs are not an initial therapeutic option for treating DED. The parameters are: “For patients with aqueous tear deficiency, punctal occlusion is a non-pharmacological treatment that can be considered when the medical means of aqueous enhancement are ineffective or impractical.”12 Thus, make sure to document in the patient’s chart the failure of your first-line therapy. Doing so sets up a defensible reason for using LACRIFILL and getting reimbursed for it.
Many insurance carriers establish policies that condition reimbursement on following the manufacturer’s directions for use, as well as the accepted standards of medical practice for using the product to treat the disease or condition. By adhering to those policies, the physician may avoid denied claims, recoupment of overpayments, and other threats from peer review. I have encountered practitioners whose therapeutic approach to treating DED was too aggressive. Ultimately, they were audited, and they had to give back their reimbursements. If you follow the PPP and DEWS II, you won’t have a problem.
The parameters describe a hierarchical approach: first, exhaust topical lubricants, eyelid hygiene, dietary modifications that may include vitamin supplements, and asking the patient if they can alter any environmental factors that may be exacerbating their DED. Once you move to the Level 2 treatment of DED that includes punctal plugs, evaluate the effectiveness of two plugs before you try four. Also, do not repeat the application of punctum plugs on a too-frequent basis. Make sure to implant LACRIFILL in an appropriate setting. Typically, that will be an office; rarely will it be an ASC. Third, you should be using a questionnaire with DED patients such as the Standard Patient Evaluation of Eye Dryness (SPEED) to track their disease’s progression over time.
How to Bill for LACRIFILL
The coding for inserting LACRIFILL is simple. These claims are reported with CPT code 68761. To support your claim for reimbursement, the documentation in your charts needs to be appropriate. When writing a diagnosis, don’t ignore the patient’s history, including the treatments you or other practitioners have tried. You must follow the payor policies, which tend to echo the AAO’s PPP. The patients you are most likely to start with as cataract surgeons will be those with compound disease. They have cataracts, they have dry eyes, and they have pretty high expectations for visual rehabilitation. Based on my years of reviewing surgical charts, comorbid dry eye disease does indeed hinder the outcomes for cataract surgery. Therefore, pretreating existing dry eye disease is probably a very good idea.
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11. Medicare Program Integrity Manual. Chapter 13–Local Coverage Determinations. Centers for Medicare and Medicaid Services. Available at https://www.cms.gov/regulations-and-guidance/guidance/manuals/downloads/pim83c13.pdf. Accessed July 18, 2024.
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