Regardless of the type of procedure, inflammation after intraocular surgery occurs and must be managed to prevent potential vision-limiting complications. This is the case with vitreoretinal surgeries, including vitrectomies, even though they are now performed with smaller-gauge instruments, higher-frequency vitreous cutters, and improved adjunctive agents.¹ To address inflammation following cataract surgery, there is a growing trend toward the use of postoperative anti-inflammatory treatments that are intended to replace topical eyedrops.² One such treatment is dexamethasone intraocular suspension 9% (Dexycu; Eyepoint Pharmaceuticals), which is formulated as a drug-encapsulating sphere in the anterior chamber (AC) that dissolves over the course of a few weeks, slowly releasing the drug and alleviating postoperative inflammation. Figures 1 and 2 present 2 methods for injecting Dexycu in phakic patients undergoing vitreoretinal surgery. In Figure 1, a paracentesis is made, and Dexycu is injected under the iris via 27-gauge cannula. In Figure 2, Dexycu is again injected under the iris but this time using a 27-gauge needle.

In a randomized, placebo-controlled, phase 3 trial, Donnenfeld and Holland showed that dexamethasone intraocular suspension, or intracameral dexamethasone (ICD), was safe and efficacious in the treatment of inflammation associated with cataract surgery.³ In vitreoretinal surgery, while all surgeons want excellent outcomes, these patients tend to have very different expectations than those who have paid out of pocket for a femtosecond laser-assisted cataract surgery with a premium intraocular lens. Still, thinking that a sustained-release intraocular steroid could provide inflammation control for patients undergoing vitreoretinal surgery and reduce their need for topical anti-inflammatory drops, the author initiated a retrospective case-matched chart review in patients undergoing various kinds of initial vitreoretinal surgery (Table 1).⁴

STUDY DESIGN AND DRUG DELIVERY

The population consisted of 2 groups with 27 patients (27 eyes) in each group: patients who received ICD at the time of vitreoretinal surgery were matched with historical controls who had received generic topical prednisolone acetate postoperatively. The primary endpoint was the proportion of study eyes with complete clearance of AC cells (ACCs) (0 cells) at postoperative day (POD) 7. The secondary endpoints were ACC clearance rates at PODs 1, 30, and 90. Safety signals were evaluated throughout the 3 months following surgery.

In the group receiving ICD, an AC paracentesis was created at the end of surgery, and ICD was injected using a 27-gauge bent cannula, which was gently inserted into the AC. The ICD was administered under the iris at approximately 180° from the paracentesis. A slight sweeping motion with the cannula helped the spherule of drug to detach from the end of the cannula and remain under the iris. In some cases, the drug migrates into the AC, where it can remain to dissolve over about 2 weeks. It is worth noting that surgeons performing this procedure should use caution to avoid iatrogenic trauma to any of the AC structures, especially when injecting under the iris where the tip of the cannula is not visible.

All patients in this study were undergoing first-time vitrectomy due to a range of intraocular pathologies, such as vitreous hemorrhage due to proliferative diabetic retinopathy, retinal tears, retinal vein occlusion, epiretinal membrane or macular holes, or retinal detachments. Some patients had comorbidities that may have predisposed them to excess inflammation unrelated to the surgical procedure. However, the surgeries in this study were less than an hour in length and relatively uncomplicated. A larger prospective study is warranted in patients who may be more prone to inflammation, such as those with a history of uveitis or those requiring a longer, more complicated surgery.

STUDY RESULTS

At POD 7, the ICD group showed significantly greater ACC clearing compared with the control group, thereby meeting the primary endpoint of the study. The ACC clearing was observed in 18 (66.7%) eyes treated with ICD compared with 10 (37%) of those treated with topical prednisolone. No eyes in the ICD group had AC inflammation requiring rescue medication at any time.

For the secondary endpoints, at POD 1 there was a statistically significant difference in ACC clearance: Those in the ICD group showed no cells in the AC at rates of 44.4%, further increasing to 85.1% by postoperative day 30 and 92.5% by postoperative day 90. The control group treated with topical corticosteroids showed ACC clearance rates of 22.2% on POD 1, which increased to 74% on POD 30 and 81.4% on POD 90. The difference between test and control treatment groups was significant after POD 1 and POD 7, but not significant at PODs 30 and 90.

Up to POD 90, adverse events (AEs) occurred in fewer patients treated with ICD (12 [44%] vs 19 [70.3%]). An increase in intraocular pressure (IOP) from baseline of any amount was recorded in 17 (62.9%) patients in the ICD group and 18 (66.6%) patients in the prednisolone group. The mean IOP did not exceed 21 mmHg in either treatment group at any visit. IOP increase of 10 mmHg or more from baseline was observed in 2 (7.4%) patients treated with ICD and 3 (11.1%) patients in the prednisolone control group. Cataract progression in phakic eyes was common: 33% in the ICD group and 75% in the control group. Other treatment-emergent AEs reported in at least 10% of eyes in either group were eye pain, foreign body sensation, vitreous floaters, corneal edema, and cystoid macular edema (CME) as determined by optical coherence tomography (OCT). Patients who received ICD responded positively, and reported that they were generally pleased at the prospect of not having to use steroid eye drops for a month after surgery.

IMPLICATIONS FOR THE PATIENT EXPERIENCE

A single administration of ICD following vitreoretinal surgery removes the onus from the patient of having to instill drops up to 4 times per day for a month, which is likely to improve inflammation control without relying on patient adherence. In observational studies of patients using eye drops, between 18.2% and 80% of patients contaminate the bottle by touching their eye or face, 11.3% to 60.6% do not instill exactly 1 drop, and 6.8% to 37.3% miss the eye altogether. Factors associated with poorer technique include older age, arthritis, and more severe visual field defect.⁵

Additionally, there may be out-of-pocket costs associated with eye drops as well as delays in obtaining drops if, for example, what is prescribed is not covered by the patient’s insurance. The many variables that impact patient adherence can be eliminated by the surgeon by administering anti-inflammatory medication at the time of surgery.

ADDITIONAL ALTERNATIVES TO TOPICAL EYEDROPS FOLLOWING VITREORETINAL SURGERY

The compound steroid-antibiotic drug, triamcinolone acetonide/moxifloxacin (Tri-Moxi; ImprimisRx), is injected transzonularly or through the pars plana after intraocular lens placement and before viscoelastic removal during cataract surgery. A retrospective analysis reviewed vitrectomized eyes that underwent cataract surgery with intraocular lens placement using either intravitreal Tri-Moxi injection along with postoperative NSAID eye drop or a standard eye-drop regimen. A total of 61 consecutive eyes (Tri-Moxi: 16, standard: 45) of 58 patients were included in the study. Considering the noninferiority margin of +0.5 grade, Tri-Moxi was shown to be noninferior to the standard intraocular inflammation control regimen at postoperative week 1 (difference of -0.042 in mean AC grade [95% confidence interval [CI] -0.483 to 0.399]) and month 1 (difference of -0.301 in mean AC grade [95% CI -0.631 to 0.030]).⁶ Tri-Moxi may not be appropriate for every patient — for example, patients who are still phakic would not be candidates for a postzonular injection of a depot antibiotic–steroid combination. However, it may be a viable alternative to eye drops for many patients.

Dexamethasone ophthalmic insert 0.4 mg (Dextenza; Ocular Therapeutix) is a corticosteroid ophthalmic insert indicated for the treatment of ocular inflammation and pain following ophthalmic surgery.⁷ Sustained release of dexamethasone is achieved through the use of a polyethylene glycol (PEG)-based hydrogel depot that expands on contact with fluid so that it is secured in the canaliculus, allowing for sustained and tapered release of preservative-free dexamethasone to the ocular surface for up to 30 days. The device softens over time and is eventually cleared through the nasolacrimal duct without the need for removal. The depot illuminates when viewed with a blue light source and yellow filter so that its presence in the canaliculus can be confirmed.⁸

A retrospective, single-center review of 20 macular surgeries performed with a dexamethasone ophthalmic implant and subconjunctival antibiotic found that only 2 patients of 20 (10%) required supplementation with topical steroid drops (both had combined phacovitrectomy). Additionally, there was no significant IOP elevation or macular edema observed on OCT at 1 month. All (7/7) patients having a second-eye surgery preferred the dexamethasone ophthalmic insert over a drop regimen.⁹

CONSIDERATIONS DURING THE COVID-19 PANDEMIC

Exposure to COVID-19 is a major concern to both patients and surgeons. In elderly patients who may be undergoing vitreoretinal or cataract surgery, options other than eye drops may be safer than leaving their home to obtain medication. Additionally, for certain types of emergent vitreoretinal surgeries, ICD offers the surgeon greater control over the possibility of postoperative inflammation, which may otherwise lead to complications that could be challenging to treat during a pandemic.

CONCLUSION

The case-control, retrospective study of dexamethasone intraocular suspension 9% showed that ICD placed in the AC at the conclusion of vitreoretinal surgery was more effective in controlling inflammation than a standard corticosteroid eyedrop regimen. The nature of the AEs recorded was consistent with the profile expected following these posterior segment surgeries. Treatment of postoperative inflammation with this ICD suspension may offer significant clinical benefits to retinal surgeons and their patients, especially those undergoing an uncomplicated vitreoretinal surgery. As always, consulting with the patient’s insurer prior to use is recommended before choosing any replacement for topical anti-inflammatory eye drops. RP

REFERENCES

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