The Value of TobraDex ST in Daily Practice

Blepharitis/meibomian gland dysfunction is commonly seen on the front lines of practice. Consider using a drug with a lower concentration of steroid – without compromising efficacy

Ocular inflammation is a problem commonly seen in practice, and blepharitis is a particularly vexing challenge. A published survey indicates that eye care professionals encounter blepharitis frequently – ophthalmologists said they observe it in more than one-third of their patients, while optometrists report seeing it in nearly half of the patients they see.

During the recent Ophthalmology 360 Virtual Summit, Joseph Kavanagh, MD, explained how he tackles this challenge, and why the approach makes practical sense. Dr Kavanagh, a cataract and LASIK surgeon who practices at Eye Associates of South Texas, described the problem, outlined a solution, presented clinical data backing up the solution, and described what success looks like in practice.

The solution, he said, involves tobramycin/dexamethasone ophthalmic suspension (TobraDex ST), which uses a lower concentration of steroid without compromising efficacy. In fact, he noted, efficacy is improved due to the drug’s unique suspension properties. “When I need to fight ocular inflammation, I turn to TobraDex ST because it has the pedigree of original TobraDex and suspension technology that offers consistent drug deliver,” said Dr Kavanagh in a recent interview with Ophthalmology 360.

The Problem
Ocular inflammation with risk for bacterial overgrowth is a common problem seen in eye care practice. Patients typically present with lid margin disease, described as an inflammatory condition that encompasses the anterior and posterior lid margins where bacteria can play a role in the physiological process. Those with lid margin disease present with either anterior blepharitis, comprising folliculitis, erythema and edema, scaling of formation of collarettes, and loss/misdirection of lashes; or posterior blepharitis/meibomian gland dysfunction (MGD), comprising erythema and edema, meibomian glands compromised by oil or thick secretions, telangiectasia, and eyelid scarring.

Bacterial overpopulation on the eyelids can lead to a number of unwanted consequences:

• Bacterial release of lipases can break down and interrupt the healthy, smooth oil layer
• Lipases can break up lipids into froth and free fatty acids
• Bacterial release of inflammatory toxins can contribute to inflammation
• Bacteria can lead to both anterior and posterior blepharitis

This unwanted activity prevents the meibomian glands to sufficiently product oil, and alters the normal lipid composition of oils.

In addition to lid margin disease, patients can experience:

• Bacterial conjunctivitis, in which they present with conjunctival redness and swelling, purulent discharge, ocular discomfort/foreign body sensation, tearing, and/or lid crusting.
• Contact lens acute red eye, in which they typically have unilateral eye pain, photophobia, epiphora, and or conjunctival redness and swelling.

Beyond these clinical conditions, there is the practical issue of providing the optimal amount of drug for maximal benefit.

The Solution
Enter TobraDex ST, which, Dr Kavanagh explained, “was designed with a purpose – to be better than TobraDex. It is made with half the concentration of dexamethasone, but includes a vehicle that will increase the viscosity of the topical agent. It increases the retention time on ocular surfaces which in turn increases the bioavailability.”  Developers accomplished this by adding xanthan gum to TobraDex. “It creates a unique interaction when it mixes with tears, increasing viscosity and retention time,” he noted, adding that there is no therapeutic or generic equivalent to the medication.

The so-called XanGen technology introduced with the ST version of TobraDex has been demonstrated to result in consistent delivery. Specifically, an analysis found that nearly all (97%) of dexamethasone remained suspended after 24 hours with ST versus just 39% for the non-ST formulation.  With the non-ST solution, “a lot of dexamethasone settled to the bottom of a graduated cylinder in much the same way it would in a bottle at the patient’s bedside.”

The Data
Improved bactericidal activity

TobraDex ST’s suspension formulation can make a significant difference in practice, as evidenced by the results of a preclinical study that assessed bactericidal activity in rabbit eyes treated with ST or the non-ST formulation. Even though the ST formulation contains 0.05% dexamethasone, compared with 0.1% in the non-ST formulation, researchers observed a more than 12-fold increased concentration of the drug in tears that had received ST, compared with the non-ST formulation, following administration of a single drop.

Increased concentration of steroid even with less steroid in the bottle

In a pharmacokinetic study involving participants requiring cataract surgery who received either the ST or non-ST formulation investigators found that the concentration of dexamethasone in the aqueous humor 2 hours after instillation was 33.7 ng/mL in patients receiving ST, versus 30.9 ng/mL in those receiving the non-ST formulation.

“That’s the really great news,” explained Dr Kavanagh. “We can give a lower dose dexamethasone and see a higher dose of dexamethasone in the anterior chamber.”

How it compared with alternative therapy

How does TobraDex ST compare with alternative therapies? Dr Kavanagh pointed to a multicenter, randomized, investigator-masked, active-controlled 15-day study involving 122 individuals. Participants with moderate to severe blepharitis/blepharoconjunctivitis were randomized to receive either TobraDex ST 1 drop 4 times a day for 2 weeks (n = 61) or azithromycin 1 drop twice a day for 2 days and then once daily for 12 days (n = 61). Investigators evaluated patients at baseline and then on days 8 and 15, looking at lid margin redness: bulbar conjunctival redness: palpebral conjunctival redness; ocular discharge; and lid swelling, itchy eyelids, and gritty eyes.

After 1 week, those treated with ST experienced a significant reduction in all evaluated signs and symptoms when compared with patients who received azithromycin. Moreover, no intraocular pressure spikes were seen in the first week in those taking ST. At the 2-week follow-up, 3 of 61 ST patients had an increase in IOP, but only 1  was >10 mmHg. Neither group experienced serious adverse events.

Success in Action
Chronic blepharitis

The value of TobraDex ST readily translates to common clinical situations. Take, for instance, the case of a 41-year-old female referred to an ophthalmologist after complaining about redness in her right eye. She has been diagnosed previously with pingueculitis. Prior to referral, she was treated for recurrent red eye with topical steroids, which she used for 5 days and stopped after her condition resolved. Unfortunately, the condition returned after steroid discontinuation.

Upon examination, the ophthalmologist observed lid erythema and MGD in both eyes. Pinguecula was seen nasally and temporally in both eyes, and sectoral episcleritis was seen nasally in the right eye. The cornea was clear and the anterior chamber quiet. The patient was diagnosed with anterior and posterior blepharitis/MGD with presumed bacterial overgrowth. Her right eye was treated with TobraDex ST, 1 drop twice a day for 2 weeks. She was seen 1 month later. The episcleritis resolved after treatment. The exam showed markedly improved blepharitis/MGD; no recurrent episcleritis in her right eye since discontinuing the medication 2 weeks earlier; and no folliculitis.

Going forward, the patient was instructed to use lid wipes for bacterial overgrowth; start TobraDex ST if her condition re-occurs; use erythromycin in both eyes at bedtime the first week of each month to control for staph; and to obtain blood work if episcleritis returned.

Staph marginal ulcer and chalazion

The second case involved a 59-year-old male complaining of pain and photophobia in the left eye for the previous 2 days. He reported a history of eyelid infections, including crusting in the morning, and no previous ocular history or surgery. Upon examination lid erythema and MGD were observed in both eyes, along with collarettes, folliculitis, and “toothpaste-like” secretions, also in both eyes. There was also a chalazion in the left upper lid. The right cornea was clear, and a 1 to 2 mm marginal ulcer with no epithelial defect was seen on the left cornea. The right anterior chamber was quiet, and rare cell was seen in the left.

The patient was diagnosed with marginal ulcer, presumed to involve staph, in the left eye, as well as anterior and posterior blepharitis/MGD with presumed bacterial overgrowth. He was treated with TobraDex ST, 1 drop in each eye 4 times daily, and instructed to use warm compresses twice daily in both eyes and hot compresses to the chalazion several times a day. He returned 1 week later with marked improvement. The chalazion was better but not resolved. Staph marginal infiltrates were less dense, and no cells were seen in the anterior chamber. MGD was improved but not resolved, and collarettes and folliculitis had decreased.

At this point, TobraDex ST was decreased to twice a day in both eyes, with continued warm compresses. Three weeks later the patient reported no further symptoms. The chalazion was almost fully resolved. Staph marginal infiltrates had almost resolved, MGD was markedly improved, and no collarettes or folliculitis was seen. The patient was instructed to use lid wipes for bacterial overgrowth, TobraDex ST once daily for a week in both eyes before stopping, and erythromycin in both eyes at bedtime for the first 2 weeks of each month.

These cases, said Dr Kavanagh, demonstrate the value of TobraDex ST, due mainly to:

• Greater bacterial activity than TobraDex
• Rapid relief, longer retention, with half the amount of steroid compared with TobraDex
• Consistent drug delivery with minimal settling, even after 24 hours