Observation of the Curative Effect of the Dexamethasone Vitreous Cavity Implant for the Treatment of Irvine-Gass Syndrome

Irvine-Gass Syndrome (IGS) is one of the most important conditions that affect visual acuity recovery after cataract surgery. Although the disease tends to heal independently, some patients still present with persistent macular edema, which eventually leads to permanent visual impairment. Most researchers consider inflammatory stimulation to be the main cause of IGS pathogenesis^[1]. The release of inflammatory mediators, including prostaglandins and vascular endothelial growth factors (VEGF), during surgery leads to blood-retinal barrier damage and increased vascular permeability, resulting in macular edema^[2]. Currently, nonsteroidal antiinflammatory drugs and glucocorticoids are used as treatment for IGS. Dexamethasone vitreous cavity implants (Ozurdex) can effectively inhibit the synthesis of various inflammatory factors, such as VEGF and prostaglandins, for long periods and reduce vascular leakage, thus reducing macular edema^[3]. The Food and Drug Administration has approved Ozurdex for the treatment of a variety of retinal diseases, including retinal vein occlusion, diabetic macular edema, and noninfectious uveitis^[3]. However, few studies have been conducted on the application of Ozurdex for IGS, and no relevant reports have been published in China. To evaluate the efficacy and safety of Ozurdex, we herein analyzed and studied the data of patients with IGS treated with Ozurdex.

Eight patients with IGS who visited the ophthalmology clinic of the Beijing Tongren Hospital between August, 2020 and June, 2022 were selected. These included six men (six eyes) and two women (two eyes). The age of the patients ranged from 55 to 87 years, with a mean of 67.12 ± 11.92 years. One patient was diabetic, two had hypertension, and no preoperative fundus-related complications were observed.

The inclusion criteria were as follows: (1) patients who had underwent conventional cataract ultrasound emulsification and posterior chamber intraocular lens implantation with smooth surgical procedures and no intraoperative complications. (2) The patient developed visual loss postoperatively, and a diagnosis of IGS was confirmed using optical coherence tomography (OCT), with or without fluorescein fundus angiography (FFA); with a best-corrected visual acuity (BCVA) that decreased by ≥ 2 lines compared to postcataract surgery using the International Standard Visual Acuity Scale^[4]. (3) Postoperative macular edema did not improve significantly after 2 months of treatment with glucocorticoids, nonsteroidal antiinflammatory eye drops, or retrobulbar injection of triamcinolone acetonide. (4) The patient had no history of glaucoma, and the intraocular pressure was normal. The exclusion criteria were as follows: (1) preoperative macular edema and other abnormalities in the macula due to various causes, such as diabetic retinopathy, retinal vein obstruction, or highly myopic macular degeneration on OCT examination; (2) history of eye surgery; (3) primary glaucoma or clinically suspected glaucoma; (4) other diseases of the eye, such as localized eye infections; and (5) serious systemic diseases.

Before injection, the affected eyes were treated with 0.5% levofloxacin drops four times per day for 3 days. Oxybuprocaine hydrochloride drops (0.4%) were used for surface anesthesia. A conventional disinfection towel was also used. The conjunctival sac was disinfected with 5% povidone-iodine and rinsed with normal saline solution. The 22G Ozurdex implantation device was inserted 3.5 mm from the corneal limbus at the 4–8 o’clock region. The needle was inserted approximately 1 mm into the sclera, turned towards the center of the eye and into the vitreous cavity until the silicone sleeve contacted the conjunctiva. The activation button was slowly pressed until a “click” was heard, and it was ensured that the button is fully pressed and locked. The needle was removed from the original path, and the puncture port was pressed using a cotton swab. After gross measurement of vision in the affected eye, tobramycin eye ointment was applied to the conjunctival sac and sterile gauze was used to cover the affected eye. Postoperative antiinflammatory drops were routinely administered to prevent infection.

Central macular thickness (CMT), BCVA, and intraocular pressure (IOP) were measured before the Ozurdex vitreous cavity injection and at 2 weeks, 1 month, 3 months, and every 3 months after implant insertion. The patients’ BCVA was checked for fractional visual acuity using the International Standard Visual Acuity Scale and then converted to logarithmic (logMAR) visual acuity at the minimum angle of resolution to calculate the mean visual acuity for statistical comparisons.

Recurrence of macular edema was defined as a decrease in BCVA of ≥ 2 rows or an increase in CMT of ≥ 100 µm from the patients previous measured value. If macular edema recurred, the Ozurdex treatment was repeated.

The Statistical Package for the Social Sciences (version 23.0; IBM-SPSS, Chicago, IL, USA) was used for statistical analysis of the data, and quantitative data were expressed as mean ± standard deviation (x ± s). Preoperative and postoperative BCVA, CMT, and IOP of the patients were compared using paired t-test, and the data at each postoperative time point were compared using multifactor analysis of variance, and the difference was considered statistically significant at P < 0.05.

Among the eight patients, the time of onset of macular edema after cataract surgery was 0.5, 1, 2, 1.5, 2, and 3 months after cataract surgery. The mean was 1.4 ± 0.5 months, and the follow-up period was 3–9 months. Seven of the eight patients received one injection, and one patient received two injections (macular edema recurred 3 months after the first injection). Basic patient information is shown in Table 1.

The mean visual acuity BCVA (logMAR) was 0.81 ± 0.26 before Ozurdex implantation, and 0.20 ± 0.12, 0.13 ± 0.09, and 0.15 ± 0.13 at 2 weeks, 1 month, and 3 months after implantation, respectively. The mean visual acuity improved at all three follow-up time points after implantation compared with pretreatment, and all differences were statistically significant (P < 0.001). The improvement in visual acuity at 2 weeks after implantation compared to that at 1 month after implantation was statistically significant (P = 0.02) (Table 2 and Figure 1A).

Figure 1.  Changes in BCVA (A) and CMT (B) before and after intravitreal Ozurdex injection in patients with Irvine-Gass syndrome. BCVA, best corrected visual acuity; CMT,central macular thickness

The mean CMT was 703.00 ± 148.88 μm before Ozurdex implantation and decreased to 258.87 ± 37.40 μm, 236.25 ± 28.74 μm, and 278.00 ± 76.82 μm at 2 weeks, 1 month, and 3 months after implantation, respectively. The mean CMT decreased at all three follow-up time points after implantation compared with pretreatment, and the differences were statistically significant (P < 0.001). The difference in the reduction of CMT at 2 weeks after implantation compared with that at 1 month after implantation was statistically significant (P < 0.05) (Table 3, Figure 1B, and Figure 2A–C).

Figure 2.  Macular OCT changes before and after intravitreal Ozurdex injection in patients with Irvine-Gass syndrome. (A) is before injection, (B) is 1 month after injection, and (C) is 3 months after injection.

The patient’s mean IOP before implantation was 12.62 ± 2.87 mmHg. The IOPs at 1 week, 1 month, and 3 months after implantation were 12.75 ± 2.12 mmHg, 12.62 ± 2.72 mmHg, and 12.12 ± 2.23 mmHg, respectively. The IOPs of all patients were within the normal range at all time points after implantation, and the differences with the preoperative IOPs were not statistically significant (P > 0.05).

Only two of the eight patients had a small amount of subconjunctival hemorrhage at the injection site, which resolved spontaneously within 1 week after the surgery. No ocular complications, such as artificial lens dislocation, vitreous hemorrhage, retinal detachment, endophthalmitis, or systemic adverse events, were observed.

IGS is the most common cause of postcataract vision loss and visual distortion and can occur 4–12 weeks after cataract surgery, with a peak incidence at 6 weeks postoperatively^[2]. The disease was first proposed by Irvine in 1953, and its clinical presentation was described in FFA by Gass in 1966; hence, the name “Irvine-Gass syndrome”^[5,6]. The incidence of the disease has decreased significantly with advances in modern cataract surgery, with only 1%–2% of the patients presenting with significant visual symptoms. However, OCT examinations can reveal subclinical macular cystoid edema in up to 41% of the patients^[7]. IGS tends to spontaneously resolve within 6 months after cataract surgery in 50% of the cases and within 2 years in 90% of the cases^[8]. However, there are still some cases of chronic, persistent macular edema resulting in photoreceptor cell damage, and permanent visual impairment in 26.8% of the affected patients^[9,10].

The pathogenesis of the disease is not fully understood, and most researchers believe that the inflammatory response is the main mechanism^[11-15]. Cataract surgical manipulation leads to the release of local inflammatory mediators, including prostaglandins and VEGF, resulting in disruption of the blood-retinal barrier, dilated capillaries, increased permeability around the macula, and fluid accumulation between the retinal layers in the macula, manifesting as macular cystoid edema. In addition, mechanical vitreous traction, retinal photodamage, and low intraoperative IOP may also be associated with morbidity. Additional risk factors for IGS include diabetes mellitus, rupture of the posterior lens capsule during cataract surgery, and the preoperative presence of ophthalmic diseases, such as macular epiretinal membrane, uveitis, and retinal vein obstruction^[15].

There is no standard or uniform protocol for the treatment of IGS. Commonly used initial treatments, such as topical nonsteroidal antiinflammatory drugs or steroid drops, oral carbonic anhydrase inhibitors (e.g., acetazolamide), and triamcinolone acetonide peribulbar injections, have shown some efficacy^[16]. However, there are still cases of refractory, persistent macular edema that do not respond well to these initial treatments, and previous studies have used vitreous cavity injections of antiVEGF drugs or triamcinolone acetonide in these cases^[17]. Although antiVEGF drugs can reduce edema, their effectiveness only lasts for approximately 1 month, and patients often require multiple injections owing to the recurrence of edema^[18]. Although triamcinolone acetonide vitreous chamber injection can inhibit the release of inflammatory factors and relieve macular edema, it also causes an increase in IOP of up to 53.2%^[19]; hence, it is not an ideal drug in terms of safety.

Several studies have reported the efficacy of Ozurdex in the treatment of cystoid macular edema in IGS^[20-23]. Meideros et al. treated nine cases of postoperative refractory macular edema with Ozurdex, and patients showed improvement in BCVA and CMT compared to baseline^[24]. Sharma et al. reported that the visual acuity of eyes treated with Ozurdex was better than that of eyes treated with antiVEGF at 1 year of follow-up, and the number of injections required was significantly less than the antiVEGF treatment injections required^[25]. Williams reported that 54% of the patients had an increase in visual acuity of at least 15 Early Treatment Diabetic Retinopathy Study letters after 3 months of Ozurdex injections^[26]. Of the eight patients in the present study, only one patient received two injections, and the remaining seven received only one injection within the 3–9 months of follow-up period. Additionally, no recurrence of macular edema was observed. At the three time points after injection, the patient's visual acuity and CMT were significantly improved compared to pretreatment measurements, which was consistent with the results of previous studies.

The safety of Ozurdex for IGS has also been widely demonstrated. Sharma et al. reported that only 3 of the 45 patients who received Ozurdex injections experienced elevated IOP^[25]. David et al. reported mild-to-moderately elevated IOP (22–33 mmHg), which were all controlled within 2 months of diagnosis by topical eye drops of 1–2 IOP-lowering drugs, without the need for filtration surgery^[12]. There have been no reports of endophthalmitis, medically induced retinal detachment, or systemic adverse events associated with IGS treated with Ozurdex injections. No ocular or systemic complications associated with the injectable drugs were identified in this study.

A multicenter study showed that 73.4% of clinicians currently choose Ozurdex for vitreous injection in IGS, suggesting that Ozurdex is the vitreous injection of choice for this disease^[25]. Although most physicians prefer to use Ozurdex as a second-line treatment option when conservative treatment has failed, a recent study showed the benefit of early intervention, as eyes treated with early Ozurdex (i.e., within 4 weeks of diagnosis) showed better benefits in terms of retinal structure and visual function than those treated with Ozurdex after 14 weeks^[25]. Therefore, when treating IGS, the patient’s visual needs, economic conditions, medical condition, etc. should be considered as opposed to simply waiting for self-healing. Clinicians can thus appropriately advance vitreous injections to reduce chronic damage to photoreceptor cells in the macula.

This study had several limitations. First, the sample size was small; thus, a larger sample size is needed to study the effects of dexamethasone intravitreal implantation. Second, the study did not include a control group; thus, a randomized controlled study is also required. Third, a longer follow-up time is needed to observe long-term effects. However, owing to the low incidence of the disease, the present study provides real-life data regarding the role of intravitreal therapy for IGS. In conclusion, the treatment of IGS with Ozurdex is safe, effective, and can significantly improve patient’s visual acuity and retinal anatomy. Further clinical application of Ozurdex for IGS is thus warranted.