A safe, effective alternative to IV

Analysis finds MKO Melt controls pain and anxiety during cataract surgery.

By Maggie Jeffries, MD

After an analysis of 610 patients, the MKO Melt was found to be an effective means for controlling pain and anxiety during cataract surgery, with the advantage of reducing the need for IV medications.

My colleagues and I at Avanti Anesthesia and the Eye Center of Texas at Kirby Glen Surgery Center designed a prospective, controlled analysis of patients undergoing cataract surgery to compare the conscious sedation efficacy of the MKO Melt (Imprimis Pharmaceuticals) to what we were already giving our patients. Of particular interest was the possibility of improving the patient experience during cataract surgery by not requiring an IV to deliver conscious sedation.

Patients were randomly assigned to one of three groups. Group 1 received oral valium (5 mg or 10 mg), group 2 received oral diazepam (5 mg or 10 mg), oral tramadol (50 mg or 100 mg) and sublingual ondansetron (4 mg) and group 3 received one to two sublingual MKO Melts. Each MKO Melt contains a mixture of 3 mg midazolam, 25 mg ketamine and 2 mg ondansetron and is administered under the tongue.

ANALYSIS FINDINGS

We found that, across all groups, additional IV medications were required 32.1% of the time, which is similar to other published studies.^1,2 Group 3, the MKO Melt group, had the lowest percentage need for IV medications at 26.5%, compared to 37.9% for group 1 and 31.8% for group 2. There was a significant difference in the need for additional IV medications between groups (P=.048), and, compared to group 1, the MKO Melt group showed a statistically significant difference in need for IV medications (P=.01). The most common reason for administrating additional IV medications was anxiety, with MKO again having the lowest percentage at 14.7% (23.3% and 18.9% for groups 1 and 2, respectively).

Furthermore, we found no significant difference between surgical or discharge times across patient groups, surgeon or patient satisfaction, or side effect profile between groups. Long axial length was not associated with a higher incidence of pain or the administration of medications for pain (P=.682). Patients with pre-existing psychiatric diagnoses and current use of narcotics or benzodiazepines did not require a statistically significant increased amount of IV medications. There were no documented cases of intraoperative bradycardia or other complications that necessitated treatment. Patients were called the day after surgery and reported high satisfaction, and no significant post-discharge side effects were reported across all groups.

CLINICAL CONCLUSIONS

Our first and perhaps most important clinical conclusion is that MKO Melt is safe. After having personally administered this drug to a few thousand patients, I have encountered no adverse events requiring the use of IV medications.

Second, it is possible to offer the MKO Melt in lieu of an IV for cataract surgery, as many centers across the country have done. We have found that there is a high chance of success with such a program if the surgeon has fast surgical times, uses intracameral lidocaine and does not mind talking the patient through the procedure if needed.

We estimate that as we gain experience with the MKO Melt, less than 15% of our patients will require IV medications after receiving it. Predicting which patients will need IV sedation is fairly straightforward. Patients with high levels of anxiety, such as those that had difficulty during their presurgical testing or do not tolerate eyedrops well, should get an IV for their surgery. After about 100 procedures, the anesthesia and nursing teams had learned the proper dosing, the timing and how to coach patient expectations. In our opinion, having an anesthesia provider present is more important than having an IV, which, in most patients, can be easily placed when needed. In fact, if you survey the nursing, anesthesia and surgical colleagues at our surgical center, MKO Melt is the preferred medication for sedation of cataract patients (as well as retina patients).

Our analysis of the MKO Melt showed that it is safe, effective and superior to diazepam in the reduction of anxiety and need for IV medications. Once integrated into daily practice, MKO Melt becomes a valuable tool for cataract surgery. OM

REFERENCES

1. Rosenfeld SI, Litinsky SM, Snyder DA, Plosker H, Astrove AW, Shiffman J. Effectiveness of monitored anesthesia care in cataract surgery. Ophthalmology 1999;106: 1256-1261.
2. Pecka SL, Dexter F. Anesthesia provider’s interventions during cataract extraction under monitored anesthesia care. Journal of the American Association of Nurse Anesthetists 1997;65: 357-360.

MicroStat produces positive Phase 3 results for mydriasis treatment

Eyenovia shares results from MIST-1 study of its microdose therapy.

By Robert Stoneback, associate editor

MicroStat demonstrated a superior mydriatic effect compared to other formulations, according to the MIST-1 study results released by MicroStat developer Eyenovia. MicroStat is a combination formulation of phenylephrine 2.5% and tropicamide 1%. In the MIST-1 study, 64 subjects were treated with MicroStat compared to formulations of tropicamide and phenylephrine.

At 20 minutes, 57% of the MicroStat group achieved 6 mm dilation or greater, compared to 38% of the tropicamide group and 0% of the phenylephrine group. At 35 minutes, 94% of eyes in the MicroStat group had 6 mm or greater dilation, compared to 78% and 1.6% in the tropicamide-only and phenylephrine-only groups, respectively. All the treatments were administered using Eyenovia’s Optejet, which uses piezo-print technology to deliver a microdose of 6 μL to 8 μL of drug to the eye.

MICRODOSING VALIDATION

MIST-1 is a pivotal study for Eyenovia, says Sean Ianchulev, MD, MPH, the company’s CEO and chief medical officer, as it helps validate not just MicroStat but also the microdosing delivery platform. With MicroStat and Optejet, medication can be delivered to the eye with much greater precision and a lower chance of drug overdosing, says Dr. Ianchulev. “We’ve been using the eye dropper paradigm for about 100 years … We’re using grandparent technology today when we have much better tools.”

Eyenovia expects results from the soon-to-be-completed MIST-2 study to be similar to those of MIST-1; the endpoints of both studies are very similar, says Dr. Ianchulev. Within 12 months of the MIST-2 results, Eyenovia plans to submit an NDA to the FDA. Hopefully, says Dr. Ianchulev, MicroStat will be available in the United States in the next 12 to 18 months.

Dr. Ianchulev added that these Phase 3 results help validate the platform for additional ophthalmology indications. In February, Eyenovia announced that the FDA accepted its IND application for its Phase 3 CHAPERONE trial, which will study the MicroPine treatment, a microdosed version of atropine used to treat myopia progression. The CHAPERONE study is scheduled to start in the first half of this year. Also, Eyenovia has a Phase 3 trial scheduled for MicroProst, a microdose treatment to lower IOP in chronic angle glaucoma patients — for which there are currently no FDA-approved treatments, Dr. Ianchulev says. OM