Cystoid macular edema (CME) is a complication of various ocular diseases, including inflammatory injuries such as uveitis and diabetes, and it can be iatrogenically induced by intraocular operations, especially cataract surgery.1
If diabetic macular edema (DME) exists before cataract surgery, it can worsen even after uneventful surgery.2 The incidence of CME in patients with uveitis undergoing cataract surgery ranges between 21% and 50%, a much higher rate than in patients without uveitis.3 This suggests that preexisting uveitic CME can worsen after cataract surgery.
The pathophysiology of uveitic CME and DME has not been fully understood. But in both cases, inflammation seems to contribute to development of macular edema. Growth factors and cytokines such as vascular endothelial growth factor (VEGF), angiopoietins, tumor necrosis factor, interleukins, and matrix metalloproteinases are upregulated as a result of inflammation and contribute to breakdown of the inner and outer blood–retinal barrier, thereby increasing vascular permeability, leading to subsequent macular edema.1–4
Triamcinolone acetonide (TA) is a synthetic corticosteroid with 5 times the antiinflammatory strength of hydrocortisone and can reduce blood–retinal barrier breakdown and downregulate VEGF expression.2,5 Various studies conducted to evaluate the efficacy of intravitreal TA injection (IVTA) have shown that IVTA is effective in reducing uveitic CME and DME and leads to improvement in visual acuity (VA).4,5 In patients with cataract and DME who are unresponsive to intravitreal anti-VEGF therapy IVTA combined with cataract surgery improves VA and decreases central macular thickness.6
In phakic eyes, intracameral injections are not able to deliver significant concentrations of drugs to the posterior segment of the eye.7 However, in a study in dogs, Waterbury reported that intracameral administration of diluted phenylephrine and ketorolac 1%/0.3% during phacoemulsification achieves therapeutic levels during surgery in both the aqueous and vitreous, and therapeutic drug levels were maintained for at least 10 hours postoperatively.8 This suggests that intracameral injection of a therapeutic agent in a pseudophakic eye can be useful to control diseases of the posterior segment of the eye, such as macular edema. In the situation of macular edema coexisting with cataract, cataract surgery with coinjection of TA intracamerally can be a therapeutic alternative.
In this study, 3 cases of intracameral injections performed in pseudophakic eyes or during cataract surgery, were reviewed to determine the effect of intracameral triamcinolone acetonide injection (ICTA) on macula edema in pseudophakic eyes.
A 74-year-old male patient with a 30-year history of diabetes presented with decreased VA in both eyes. Corrected distance visual acuity (CDVA) was 20/63 in the right eye and 20/200 in the left eye. Slitlamp examination demonstrated severe dense nuclear cataract in both eyes. Wide fundus photography shows nonproliferative diabetic retinopathy in both eyes. On macular optical coherence tomography, the left eye showed severe macular edema and a foveal thickness of 351 μm. Endothelial cell density (ECD) and IOP were 2629 cells/mm2 and 19 mm Hg, respectively.
Phacoemulsification and intraocular lens (IOL) implantation were performed in the left eye. To avoid the worsening of DME, 0.1 mL intracameral injection of TA (TRIAM) was given at the end of cataract surgery (Figure 1). After cataract surgery, levofloxacin ophthalmic solution (Cravit eye drops 0.5%) and fluorometholone ophthalmic solution (fluorometholone eye drops 0.1%) were used 4 times a day for 4 weeks. Bromfenac ophthalmic solution (Bronac eye drops) was used 2 times day for 4 weeks to prevent CME.
Two months after cataract surgery, intraocular pressure (IOP) was 11 mm Hg and foveal thickness decreased to 272 μm, and VA improved to 20/50 (Figure 2). However, ECD decreased from 2629 to 2008 cell/mm2 because dense nuclear cataracts require more ultrasound energy.
A 73-year-old man was referred for IOL dislocation in the right eye. He had cataract surgery on both eyes 3 years previously at a local clinic. At the first visit, the CDVA was 20/50. The dislocated IOL was removed, and anterior vitrectomy was performed. An iris claw IOL was implanted as retropupillary fixation. However, the CDVA gradually decreased to 20/50 because of pseudophakic macular edema. The patient was treated with topical 1% prednisolone ophthalmic solution (Pred Forte eyedrops) every 2 hours and oral methylprednisolone (Methylon Tab) for 2 months. However, macular edema increased, with a foveal thickness of 370 μm.
Subsequently, ICTA was performed with the same method described above (Figure 3). After 1 month, foveal thickness dramatically improved to 290 μm, and CDVA returned to 20/20 (Figure 4). Before injection, ECD and IOP were 1675 cell/mm2 and 13 mm Hg, respectively, whereas after 1 month, the values were stable, 1793 cell/mm2 and 16 mm Hg.
A 58-year-old man complained of decreased VA in his left eye. The patient had a mature cataract and crystalline lens dislocation. At the first step, ICCE and anterior vitrectomy were performed. Then, secondary IOL implantation with retropupillary fixation of an iris claw lens was followed 1 month later. The CDVA increased from counting fingers to 20/40. However, 7 months after secondary IOL implantation, severe CME occurred (Figure 5, A).
Initially, retrobular TA injection was performed. Before injection, foveal thickness was 760 μm, and VA was 20/400; however, the treatment did not work (Figure 5, B). One month later, foveal thickness reached 780 μm, for which additional intravitreal TA injection was given. One month after the second treatment, foveal thickness was slightly decreased to 621 μm, whereas a large amount of macular edema remained (Figure 5, C). One month after IVTA, foveal thickness was 665 μm.
Thus, removal of the iris claw IOL was considered as a therapeutic option. However, before lens removal, ICTA was tried to control iris inflammation and macular edema. One month after treatment, foveal thickness dramatically decreased to 359 μm (Figure 5, D). ECD and IOP were not changed after ICTA. However, within 4 months, macular edema had recurred, and foveal thickness reached 647 μm (Figure 5, E). One more ICTA injection was given; macular edema was dramatically improved at 2 weeks later. Foveal thickness decreased to 295 μm, and VA was 20/100 (Figure 5, F). Therefore, we did not remove the IOL.
Intracameral injection is administration of a drug into the anterior chamber of the eye. It is well known that intracameral injections are not able to deliver significant concentration of drugs to the posterior segment of the eye.9 They can, however, be used to deliver drugs into the anterior segment, such as delivery of antibiotics in open-globe trauma to prevent endophthalmitis and corticosteroids to control inflammation of the anterior segment of the eye after cataract surgery.7,10,11
In 2006, the prospective, multicenter, European Society of Cataract and Refractive Surgeons endophthalmitis prophylaxis study reported that prophylactic intracameral antibiotic injection at the end of cataract surgery reduced the rate of endophthalmitis significantly. The 2014 American Society of Cataract and Refractive Surgery endophthalmitis prophylaxis survey found that 50% of the 1147 global respondents were using intraocular antibiotic prophylaxis, and vancomycin was the most commonly used antibiotic. However, it also revealed that prophylactic intracameral vancomycin injection at the end of cataract surgery can cause hemorrhagic occlusive retinal vasculitis.12 Although it is thought to be a type III hypersensitivity reaction, this may suggest that drugs in the anterior chamber can affect the posterior segment of a pseudophakic eye, as proposed by Waterbury.8,13
TA is the most widely used corticosteroid for treatment of uveitic CME and is also used for treatment of DME.4,14 When injected intravitreally, TA has a mean half-life of 18.6 days in nonvitrectomized eyes and 3.2 days in postvitrectomized eyes.4 Although dexamethasone is 3 times more potent than TA, being a water-soluble small molecule, it is rapidly cleared from the vitreous, with an estimated vitreal half-life of 5.5 hours in humans.4 Thus, it is used as a slowly dissolving implant form (Ozurdex) when injected intravitreally.14 Thus, TA can act for a longer duration than dexamethasone when it is injected intracamerally.
One of the potential side effects of corticosteroid administration by any route is increased IOP. Gungor et al. compared intracameral TA and dexamethasone injection.15 In this study, the mean IOP values at 1 day postoperatively were significantly higher in the TA group than in the dexamethasone group (P = .009). The highest IOP in the TA group was 24.0 mm Hg and stabilized in a few days. However, there was no statistically significant difference in the IOP value between the 2 groups at postoperative days 7 and 30. In our cases, there was no significant IOP elevation after injection.
According to an in vitro study conducted by Chang et al., TA showed toxicity on the cultured endothelium.16 In a rabbit eye study, TA was injected intracamerally to investigate its effect on the corneal endothelium and showed reduced microvilli, but there was no statistically significant difference in the endothelial count or central corneal thickness at 2 hours after the experimental procedure.15 In our cases 2 and 3, there was no significant ECD changes. However, in case 1, preoperative ECD of 2629 cells/mm2 decreased to 2008 cell/mm2 2 months after cataract surgery. The patient had a severe dense nuclear cataract, which may damage corneal endothelial cells during surgery due to more ultrasound energy.17
In the pseudophakic eye, intracameral injection has some advantages compared with intravitreal injection. First, it can control inflammation of the anterior chamber more directly and also can affect the posterior segment of the eye. Low-grade uveitis is the common hypotheses to explain recalcitrant CME that can complicate iris claw IOLs.18 In chronic, medication-resistant, CME from iris-fixated IOLs, removal of the iris-fixated implant is recommended.18 However, in our case, intracameral TA injection was effective in such a situation. Second, intracameral TA can help to avoid further risk for infections. Culture-positive infectious endophthalmitis after IVTA has a reported incidence of 0.45% to 0.87%.4 If a surgeon injects TA during cataract surgery, further risk for endophthalmitis by additional procedure of intravitreal injection can be avoided. Third, unlike intravitreal injection, TA is easier to be irrigated out of the anterior chamber. With IOP elevation, intravitreally injected TA or implanted dexamethasone is very difficult to remove.
In conclusion, intracameral TA injection in pseudophakic eye was effective to control macular edema associated with diabetes and uveitis. As a result, TA injection can be a possible candidate for managing CME in patients expected to undergo cataract surgery or those with pseudophakia.
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