The journey of a topical glaucoma medication is a complicated one. First, the doctor must prescribe the medication. Then, the prescription is sent to the pharmacy, and it must be filled as written or perhaps substituted for a similar medication, which may require a phone call for clarification. Next, the patient has to get to the pharmacy to pick up the medication. Some patients can take their own vehicle; others rely on friends or family or public transportation. Once the patients have the medication in their hands, they have to remember to take it, sometimes up to 4 times a day, and they have to remember to continue taking it each day for an extended period of time. After they remember to take it, they must be able to instill the medication in their eye. This seems like an easy task until you ask one of your family members to put in a drop and watch as they struggle. Alas, the prescription medication has been delivered, but the journey does not end. The medication lingers on the surface, usually not the intended target because most medications need to work inside the eye and can cause issues with the ocular surface and surrounding tissues. This can lead to conjunctival injection and pigmentary changes of the adnexa.

Given this treacherous journey, it should come as no surprise that nontopical options are becoming more available. Options include intravitreal, intracameral, subconjunctival, and intracanulicular approaches; drug-eluting rings; and contact lenses. We are able to literally take the medications out of patients’ hands and simplify their medication regimen. These simplified medication regimens can make a world of difference.

Nontopical Glaucoma Treatments

Surgeons are becoming more comfortable with nontopical options, likely due to the success of intracameral antibiotics around the world and in the United States.^1,2 But when it comes to intracameral steroids, surgeons are a bit more hesitant. A major reason for avoiding intracameral steroids is the risk for steroid-induced ocular hypertension. While anyone can develop a steroid-induced rise in intraocular pressure (IOP), patients with glaucoma are at higher risk.³ And once a medication is placed inside the eye, it is not as easy to stop compared to topical medications. As with any decision, we need to balance the efficacy with the safety. Below, we will review some of the options available to replace topical steroid drops.

Dextenza (Ocular Therapeutix) is a sustained-release intracanalicular dexamethasone insert that is placed in the canaliculus around the time of surgery. It contains 0.4 mg of active pharmaceutical product and delivers a sustained and steady dose of drug over the course of 30 days. In the phase 3C study in which patients underwent cataract surgery and either received the Dextenza implant or took topical prednisolone acetate 1%, 7% of patients in the Dextenza group had an IOP increase following surgery.⁴ However, according to the investigators, the IOP increase was due to cataract surgery and not the implant. Three percent of patients in the topical prednisolone group had IOP increases following surgery, and again this was attributed to the cataract surgery and not the steroid. In patients who received an intervention for the elevated IOP, a paracentesis or topical medication was given, or a combination of both was administered. No patient in either group had sustained IOP elevation during the study or needed further surgical intervention.

Available intraocular steroids include dexamethasone and triamcinolone, and they can be placed in the anterior or posterior chamber or in the vitreous in the posterior segment. One study compared dexamethasone to triamcinolone in 60 eyes of 60 patients who underwent cataract surgery.⁵ Eyes in group 1 (30 eyes) were injected with 0.4 mg/0.1 mL dexamethasone into the anterior chamber, and eyes in group 2 (30 eyes) were injected with 2 mg/0.05 mL triamcinolone acetonide into the anterior chamber. All eyes received a topical prednisolone acetate taper following surgery. Preoperative IOP in both groups was less than 21 mmHg. Mean IOP values at the postoperative first day were significantly higher in group 2 (19.2 mmHg) than in group 1 (16.1 mmHg). The mean IOPs on days 7 and 30 were 14.2 mmHg and 14.0 mmHg in both groups, respectively. Given these results, both steroid options seem to be safe following cataract surgery in normal patients, with dexamethasone having slightly lower IOP on day 1.

Dexycu (EyePoint Pharmaceuticals) is a dexamethasone intraocular suspension that is indicated for the treatment of postoperative inflammation. It is typically placed just behind the iris at the completion of cataract surgery. In the phase 3 clinical trial evaluating the safety and efficacy of Dexycu compared to topical prednisolone acetate 1% in patients who underwent cataract surgery alone, 11% of the Dexycu patients had an incidence of elevated IOP, and 1 patient required additional treatment with resolution by 8 days postoperatively.⁶ In all patients with increased pressure, the IOP measured 1 day postoperatively was less than 21 mmHg.

But what about patients who have glaucoma? As mentioned earlier, they are at greater risk for steroid-induced IOP spikes. A retrospective study performed in 2009 looked at intracameral injection of 0.1 mL of 4 mg/mL dexamethasone compared to topical prednisolone acetate 1% following cataract surgery.⁷ There was a significant increase in IOP of 2.3±0.7 mmHg (preoperative IOP was 15.8±0.9 mmHg) 1 day after cataract surgery that returned to near-baseline levels after 1 month, independent of treatment group or diagnosis of glaucoma. In the nonglaucomatous patients, IOP was reduced following cataract surgery at 30 days postoperatively in both the intracameral and topical groups. In the glaucomatous eyes with topical steroid, the IOP was reduced at 30 days postoperatively (15.2±1.1 mmHg preoperatively and 14.1±0.7 mmHg postoperatively) but was increased slightly in the intracameral dexamethasone group (15.1±0.6 mmHg preoperatively and 16.3±1.3 mmHg postoperatively). It is notable that in 2009 the currently available minimally invasive glaucoma surgery devices did not exist, so all of these patients underwent cataract surgery alone. Also, the level of severity of glaucoma was not noted. Assuming it was mild, an IOP of 16 mmHg is probably reasonable. And because patients were only followed for a month, the IOP could have returned to baseline at a longer interval. Overall, it seems reasonable to use intracameral dexamethasone in patients with glaucoma who undergo cataract surgery alone.

A retrospective study by Kindle et al looked at patients with open-angle glaucoma who had concurrent cataract surgery and implantation of a trabecular microbypass stent (iStent; Glaukos), divided into 2 groups.⁸ The first group received a standard topical regimen of postoperative medications consisting of an antibiotic (moxifloxacin 0.05% 4 times a day for 1 week), a nonsteroidal anti-inflammatory drug (NSAID) (bromfenac 0.07% or nepafenac 0.3% once daily for 4 weeks), and a steroid (difluprednate 0.05% or prednisolone acetate 1.0% tapered over 4 weeks). The second group of patients had a 0.2-mL pars plana intravitreal injection of triamcinolone, moxifloxacin, and vancomycin (15 mg/1 mg/10 mg/mL concentration; Tri-Moxi-Vanc; Imprimis Pharmaceuticals) at the time of surgery and a topical NSAID drop daily for 4 weeks after the procedure. There were 483 eyes in the study, 234 in the intravitreal injection group, and 249 in the standard topical group. Mean preoperative IOP was 17.78±5.29 mmHg in the intravitreal group and 19.00±6.04 mmHg in the topical group. At 3 months postoperatively, the mean reduction in glaucoma medications was 0.24 in the intravitreal group and 0.80 in the topical group, and the mean IOP reduction was 2.59 mmHg in the intravitreal group and 3.63 mmHg in the topical group. The difference in IOP reduction was not statistically significant between the 2 groups. The difference in glaucoma medication reduction was statistically significantly different, however. Pressure spikes were detected at 54 (5.7%) of 936 postoperative visits in the intravitreal group and at 37 (3.7%) of 996 visits in the topical group. The majority of IOP spikes in both groups happened at the 1-day visit. This study showed that intravitreal steroid medications can safely be used in patients with glaucoma who undergo cataract surgery plus trabecular meshwork bypass stenting, although glaucoma medication reduction is slightly less than with topical steroid.

The same group studied patients with glaucoma who received intracameral antibiotic, steroid, and NSAID (Dex-Moxi-Ketor; Imprimis Pharmaceuticals) following cataract plus trabecular meshwork bypass stent.⁹ One hundred thirty-two eyes received an injection of Dex-Moxi-Ketor in the anterior chamber followed by once-a-day topical combination prednisolone, antibiotic, and NSAID for 1 month. Three months postoperatively, the mean reduction in glaucoma medications was 0.69, and the mean reduction in IOP was 2.0 mmHg (preoperatively 17.5±4.0 mmHg, postoperatively 15.3±3.7 mmHg). Spikes in IOP occurred in 14% of patients who had intracameral injection, with 85% of spikes happening on postoperative day 1. When compared to the above study, there was no statistically significant difference between the groups in any category.

Another study of patients with glaucoma who underwent cataract surgery plus supraciliary stents (Cypass; Alcon) compared intracameral antibiotic, steroid, and NSAID to intracameral antibiotic plus topical steroid.¹⁰ Both groups took a topical steroid for 1 month postoperatively. Preoperative IOP in the topical group was 16.91±4.27 mmHg, and in the intracameral steroid group, it was 19.70±7.27 mmHg. At 6 months postoperatively, IOP was 15.15±4.13 mmHg in the topical group and 13.77±2.01 mmHg in the intracameral steroid group. The difference was not statistically significant. In the intracameral steroid group, the number of glaucoma medications was reduced from 1.28±1.07 preoperatively to 0.27±0.67 postoperatively, and in the topical group, the number of glaucoma medications was reduced from 2.46±1.07 preoperatively to 1.15±1.18 postoperatively. There were no IOP spikes recorded in either group during this study.

Summary

There are a variety of options available to replace topical medications, and there is growing evidence that they are safe and effective for patients with glaucoma. Taking medications out of patients’ hands and putting them in the eye will be a huge advantage and improve quality of life. GP

Michael Greenwood, MD, is a cataract, glaucoma, refractive, and corneal surgeon at Vance Thompson Vision in Fargo, North Dakota. He reports consultancy to Ocular Therapeutix and Alcon. Reach him at michael.greenwood@vancethompsonvision.com.

References

1. Herrinton LJ, Shorstein NH, Paschal JF, et al. Comparative effectiveness of antibiotic prophylaxis in cataract surgery. Ophthalmology. 2016;123(2):287-294.
2. Haripriya A, Chang DF, Ravindran RD. Endophthalmitis reduction with intracameral moxifloxacin in eyes with and without surgical complications: results from 2 million consecutive cataract surgeries. J Cataract Refract Surg. 2019;45(9):1226-1233.
3. Becker B, Mills DW. Corticosteroids and intraocular pressure. Arch Ophthalmol. 1963;70:500-507.
4. Tyson SL, Bafna S, Gira JP, et al; Dextenza Study Group. Multicenter randomized phase 3 study of a sustained-release intracanalicular dexamethasone insert for treatment of ocular inflammation and pain after cataract surgery. J Cataract Refract Surg. 2019;45(2):204-212.
5. Gungor SG, Bulam B, Akman A, Colak M. Comparison of intracameral dexamethasone and intracameral triamcinolone acetonide injection at the end of phacoemulsification surgery. Indian J Ophthalmol. 2014;62(8):861-864.
6. Donnenfeld ED, Solomon KD, Matossian C. Safety of IBI-10090 for inflammation associated with cataract surgery: Phase 3 multicenter study. J Cataract Refract Surg. 2018;44(10):1236-1246.
7. Chang DT, Herceg MC, Bilonick RA, Camejo L, Schuman JS, Noecker RJ. Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma. Clin Ophthalmol. 2009;3:345-355.
8. Kindle T, Ferguson T, Ibach M, et al. Safety and efficacy of intravitreal injection of steroid and antibiotics in the setting of cataract surgery and trabecular microbypass stent. J Cataract Refract Surg. 2018;44(1):56-62.
9. Evans JA, Greenwood MD, Ibach MJ, Sudhagoni RG, Berdahl JP. Safety and efficacy of intracameral vs intravitreal vs topical steroid, antibiotic, and NSAID after cataract and trabecular bypass surgery. Presented at ASCRS Virtual Annual Meeting; May 16, 2020.
10. Greenwood MD, Brubaker JW. Safety and efficacy of intracameral steroid, NSAID, and antibiotic vs topical medications for cataract surgery and supraciliary microstent. Presented at ASCRS Virtual Annual Meeting; May 16, 2020.