8 minute read
Ophthalmic Inserts, Promising Alternatives to Eye Drops?
from CAKE Magazine Issue 05: The ebook version ('The Art Issue', ASCRS 2020 Virtual Edition)
by Media MICE
by Konstantin Yakimchuk
In ophthalmology, corticosteroids are widely used for postoperative control of pain and inflammation. While steroid-based supportive therapy aims to diminish ocular inflammation, it is potentially followed by a plethora of secondary complications including elevated intraocular pressure, glaucoma, slow tissue regeneration, pain and impaired vision. 1
However, traditional eye drops may no longer satisfy ophthalmologists, since only a very small volume is actually delivered to the internal eye tissues — even if application recommendations are precisely followed. 2 Moreover, liquid drainage through the nasolacrimal channel, reduced corneal permeability and blinking are natural barriers which diminish the efficiency of standard eye drops. 3 Besides, eye drops are directly diluted by the tear film.
Thus, novel methods of drug delivery to the intraocular tissues are, indeed, needed. One such technique has been described by Brooks et. al., from the Duke University Eye Center in Durham, North Carolina and University of Illinois at Chicago, Illinois, U.S., in the recent issue of Clinical Ophthalmology. 4
A comprehensive review by Brooks et. al. described the applications of
For some patients, eye drops aren’t an option.
intracanalicular sustained-release dexamethasone (Dextenza, Ocular Therapeutix, Bedford, Maine, U.S.) to reduce postoperative ocular inflammation and pain. The review strongly advocates punctal plugs as an effective method to deliver therapeutic agents; while the dexamethasone intracanalicular insert might replace eye drops in near future due to clear advantages, such as continuous drug administration into the eyes. 5
This method has been already approved by the Federal Drug Administration (FDA), especially for the suppression of postoperative inflammation. Dexamethasone has been efficiently used to inhibit postoperative inflammation and pain after ocular surgery. 6 Moreover, it is well tolerated by ocular tissues. To obtain an expert’s opinion on Dr. Brooks’ review, Dr. Harvey Uy, clinical associate professor of ophthalmology, University of the Philippines and medical director at Peregrine Eye and Laser Institute in Makati, the Philippines, was invited to comment on the study.
According to Dr. Uy, therapeutic management after cataract surgery is primarily based on the proper control of postoperative surgery. Currently, the standard care approach implements the installation of topical drops with antibiotics and corticosteroids. Although this approach proved to be highly effective, poor compliance may cause complications and insufficient outcomes.
Novel Techniques in the Management of Poor Compliance
Longer-acting transzonular triamcinolone-moxifloxacin suspension (Dropless, Imprimis Pharmaceuticals, San Diego, California, U.S.) is one of the most effective methods to diminish the troubles with poor compliance. As Dr. Uy stated, he and his colleagues “have used this method satisfactorily for several years now in selective fashion for patients who are unable to apply postoperative drops and for patients with concomitant macular edema amenable to corticosteroid therapy.”
Are there any contraindications to transzonular triamcinolone-moxifloxacin suspension? According to the expert, limitations of this method include transient postoperative errors, contraindication for eyes with zonular weakness, and the necessity of extra intraocular maneuvers.
Another technique uses sustainedrelease dexamethasone punctual plug implants (Dextenza, Ocular Therapeutix, Bedford, Maryland, U.S.). Dr. Uy noted that: “the authors of this article have extensively reviewed the literature and correctly conclude that this method achieves adequate postoperative control with no significant safety issues.” Importantly, this novel technique is easy to operate and the probability of making an error is rather low.
Preclinical Studies and Implementations in Clinical Practice
Did preclinical studies evaluate the safety of intracanalicular plugs? For decades, animal models remain a vital tool for testing novel therapeutic approaches in ophthalmology. In particular, no effects on intraocular pressure or local toxicity were observed when dexamethasone was released into the dog canaliculi using intracanalicular depots. 7 Moreover, urine and blood samples obtained from dogs treated with dexamethasone depots were analyzed for possible toxic effects of this type of corticosteroid delivery. 8 Notably, no adverse effects were detected in dexamethasonetreated dogs when compared to placebo.
Has this technique been already implemented in clinical practice? Several clinical studies have been performed. In particular, a recent randomized study applied this technique for cataract surgery. According to the study description, dexamethasone was inserted into the inferior canaliculus during operation. 9 Continuous release of dexamethasone abolished ocular pain and eliminated anterior chamber cells after one week of treatment.
Also, a recent study by Tyson et. al. has evaluated the efficacy of intracanalicular corticosteroid inserts for the suppression of inflammation following cataract surgery. The results demonstrated significant inhibition of inflammation and no difference in the adverse effects when compared to control treatment. 10
Moreover, the patients themselves strongly advocate for the intracanalicular corticosteroid insert. When the patients who received the dexamethasone intracanalicular insert following cataract surgery were questioned regarding their experience about the method, the majority of the patients characterized their experience with the technique as “very convenient” and were willing to recommend it to relatives and friends. 11
In addition to the limitations of the method, are corticosteroids completely safe?
Immunosuppressive functions of steroids are well known. In line with this, physicians should be careful prescribing these drugs for patients with acute ocular infections, since corticosteroids may suppress both antimicrobial immune response and the mechanisms of wound healing. Both viral and fungal infections might be aggravated. 12 Furthermore, treatment with topical steroids was associated with symptoms of ocular surface disease and active disease progression. 13
Are there any disadvantages of intracanalicular corticosteroid insert?
Dr. Uy emphasized:
“The main disadvantage of this approach is cost effectiveness, as the cost of a branded bottle of steroid drops is only a fraction of the cost of the intracanalicular plug. When finances permit, the sustained release approach provides improved patient compliance with no safety concerns.”
However, when available resources of the healthcare system are restricted, eye drops or the transzonular technique would be more costeffective, even considering their limitations.
Perhaps the best solution would be to prescribe the insert for patients who fail to reliably introduce eye drops and maintain follow up visits, and where there is a lack of additional care and hypersensitivity to postoperative therapeutic drugs. In particular, intracanalicular corticosteroid inserts might be applied for retinal, corneal, glaucoma and other types of surgeries, which may potentially be associated in problems with accessing the palpebral fissure to apply eye drops.
According to Brooks and co-authors, the described drug delivery technique might significantly overcome weaknesses of current delivery systems in ophthalmology, while effectively reducing the post-surgical inflammatory process. The authors suggested that intracanalicular delivery might significantly abate both the disadvantages of topical eye drops and the toxicity of preservative components in topical medicines.
To support this statement, Dr. Uy pointed out that “the introduction of the dexamethasone implant is a very welcome addition to the eye surgeon’s toolkit.” Moreover, additional studies are required to fully estimate the potential therapeutic advantages of this method.
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P, Pleyer U. Dexamethasone Intraocular Suspension: A Long-Acting Therapeutic for Treating Inflammation Associated with Cataract Surgery. J Ocul Pharmacol Ther. 2019;35(10):525-534. Renfro L, Snow JS. Ocular effects of topical and systemic steroids. Dermatol Clin. 1992;10:505-512. Driscoll A, Blizzard C. Toxicity and Pharmacokinetics of Sustained-Release Dexamethasone in Beagle Dogs. Adv Ther. 2016:33(1);58-67.
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References:
1 Chang DT, et al. Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma. Clin Ophthalmol. 2009;3:345-355. 2 Hermann MM, Ustundag C, Diestelhorst M.
Electronic compliance monitoring of topical treatment after ophthalmic surgery. Int
Ophthalmol. 2020;30(4):385-390. 3 Gaudana R, Ananthula HK, Parenky A, Mitra AK.
Ocular drug delivery. AAPS. 2010;12(3):348- 360. 4 Brooks CC, Jabbehdari S, Gupta PK.
Dexamethasone 0.4mg Sustained-Release Intracanalicular Insert in the Management of Ocular Inflammation and Pain Following Ophthalmic Surgery: Design, Development and Place in Therapy. Clin Ophthalmol. 2020;14:89-94. 5 Chen H. Recent developments in ocular drug delivery. J Drug Target. 2015;23(7-8):597-604. 6 Grzybowski A, Brockmann T, Kanclerz 9 Walters T, et al. Sustained-release dexamethasone for the treatment of ocular inflammation and pain after cataract surgery. J Cataract Refract Surg. 2015;41(10): 2049- 2059. 10 Tyson SL, Bafna S, Gira JP, et al. Multicenter randomized phase 3 study of a sustainedrelease intracanalicular dexamethasone insert for treatment of ocular inflammation and pain after cataract surgery. J Cataract Refract Surg. 2019;45(2):204-212. 11 Gira, J. P. et al. Evaluating the patient experience after implantation of a 0.4 mg sustained release dexamethasone intracanalicular insert (Dextenza): results of a qualitative survey. Patient Prefer Adherence. 2017;11:487-494. 12 Srinivasan M, Mascarenhas J, Rajaraman R, et al. Corticosteroids for bacterial keratitis: the Steroids for Corneal Ulcers Trial (SCUT). Arch
Ophthalmol. 2012;130(2):143-150. 13 Cho CH, Lee SB. Clinical analysis of microbiologically proven fungal keratitis according to prior topical steroid use: a retrospective study in South Korea. BMC Ophthalmol. 2019;19(1):207.
Contributing Doctor
Dr. Harvey S. Uy is a clinical associate professor of ophthalmology, University of the Philippines, and medical director, Peregrine Eye and Laser Institute in Makati, the Philippines. He completed fellowships at St. Luke’s Medical Center and the Massachusetts Eye and Ear Infirmary and has been a pioneer in femtosecond cataract surgery, accommodation restoration by lens softening, modular intraocular lenses, and intravitreal drugs. He has published over 50 peer reviewed articles and is on the editorial board of American Journal of Ophthalmology Case Reports. He is a former president of the Philippine Academy of Ophthalmology and current council member of the Asia Pacific Vitreo-retina Society. He received the Jose Rizal Research Award from the Philippine Medical Association, the Xavier School Exemplary Alumni Award, and Achievement Awards from the American and Asia Pacific Academies of Ophthalmology. Dr. Uy has also delivered more than 400 scientific lectures worldwide.
harveyuy@yahoo.com
