Pseudophakic cystoid macular edema (CME) is a condition in which fluid accumulates in the intercellular spaces of the macular retina after cataract surgery, causing cystoid edema. When it occurs specifically after cataract surgery, it is called Irvine-Gass syndrome.
Clinically significant CME occurs in 1–3% of cases after uncomplicated phacoemulsification 2). Most cases respond well to topical anti-inflammatory agents, but treatment-resistant cases (approximately 0.02%) may result in permanent vision loss 2).
The incidence of clinically significant CME has been reported to be up to 2% 1). Most cases follow a self-limited course with spontaneous resolution, but treatment is required in cases that persist or worsen 1).
Symptoms of CME usually become apparent within a few weeks after surgery.
In early or mild cases, patients may not notice vision loss, but moderate to severe cases lead to obvious vision loss.
Pathologically, it is a cystoid change in the outer plexiform layer and inner nuclear layer. Tissue fluid tends to accumulate especially in the outer plexiform layer (Henle fiber layer) around the fovea. The cyst septa are formed by Müller cells and axonal fibers.
Acute CME
Onset: Peaks at 4–12 weeks postoperatively.
Fundus findings: Edema in the macula, with a petaloid cystoid pattern centered on the fovea.
OCT findings: Retinal thickening with cystoid changes in the macula.
Course: Most resolve spontaneously within 3–4 months.
Chronic CME
Definition: Persisting for 6–9 months or longer.
Tissue changes: May lead to permanent retinal fibrosis.
Photoreceptor damage: Even after edema resolves, permanent vision loss may remain due to changes in photoreceptor structure.
Role of NSAIDs: Also useful in managing chronic CME, but caution is needed for recurrence after discontinuation of treatment1).
It often peaks 4 to 12 weeks after surgery. In many cases, it resolves spontaneously within 3 to 4 months, but chronic cases lasting more than 6 months can occur. If vision loss persists, you should see an ophthalmologist early.
Intraocular inflammation plays a central role in the development of CME. Tissue damage from cataract surgery triggers an inflammatory cascade, leading to breakdown of the blood-retinal barrier and increased vascular permeability.
Risk factors are as follows2).
Diabetic patients have a higher risk of developing CME even without diabetic retinopathy1).
Epiretinal membrane (ERM) is an important risk factor for CME, and the risk increases with higher preoperative central retinal thickness. It is recommended to perform spectral-domain OCT before surgery to check for the presence of an epiretinal membrane that may be missed on fundus examination1).
Even without diabetic retinopathy, the risk of developing CME is increased 1). Therefore, combination therapy with steroids and NSAIDs eye drops is recommended, and if diabetic retinopathy is present, additional depot injection of triamcinolone may be considered 1).
Diagnosis of CME is made by combining clinical findings and imaging tests.
| Examination Method | Features | Role |
|---|---|---|
| OCT | Non-invasive | Standard imaging diagnosis 2) |
| FA | Petalloid fluorescein leakage | Gold standard |
| Fundus examination | Petalloid cysts | Initial screening |
Snellen visual acuity testing alone may underestimate the impact of CME on visual function2).
Combined use of NSAIDs and steroid eye drops is an evidence-based recommendation for preventing inflammation and CME after routine cataract surgery1).
The ESCRS PRIMED randomized controlled trial showed that the combination of bromfenac 0.09% (twice daily) and dexamethasone 0.1% (four times daily) was more effective in preventing CME than either agent alone1)2).
Key evidence is shown below.
Short-term effects of NSAIDs eye drops on visual recovery have been demonstrated, but Level I evidence for improvement in long-term prognosis beyond 3 months has not been established2).
In diabetic patients, combined use of steroid and NSAID eye drops is recommended 1).
First-line treatment for CME is topical NSAIDs or steroids 1). However, evidence to establish the optimal treatment is currently insufficient 1).
The main therapeutic agents are as follows:
NSAID administration for 2–3 months may not improve visual acuity, but improvement may be seen with longer administration of 3–4 months 1). Attention should be paid to recurrence of CME after discontinuation of treatment 1).
If improvement is insufficient, change the type of NSAID (e.g., nepafenac, bromfenac) and observe for an additional 4–6 weeks. If still no improvement, consider intravitreal steroid injection. In refractory cases, sub-Tenon triamcinolone injection is also an option.
Nonsteroidal anti-inflammatory eye drops are also used for prevention of CME after cataract surgery. For persistent CME, vitrectomy with internal limiting membrane peeling or vitrectomy with cystotomy have been reported.
Multiple RCTs have shown that combined use of NSAIDs and steroid eye drops is effective for prevention 1). Prophylactic administration is especially recommended for high-risk patients with a history of diabetes or uveitis. It is important to continue the prescribed eye drops as directed.
Inflammation plays a central role in the pathogenesis of CME. The tissue invasion of cataract surgery triggers the following inflammatory cascade.
The exact mechanism of CME is not yet fully understood. In addition to the inflammatory mechanisms above, the following factors are also suggested to be involved.
CME can cause permanent vision loss even after edema resolves. This is thought to be due to irreversible changes in photoreceptor structure caused by chronic edema.
Surgical tissue trauma releases inflammatory mediators such as VEGF and prostaglandins, increasing the permeability of the blood-retinal barrier. As a result, fluid leaks from capillaries around the fovea, forming cystoid macular edema. For details, see the section on Pathophysiology and Detailed Mechanisms.
Intravitreal injections for treatment-resistant CME are being investigated, but evidence is limited1).
According to ESCRS guidelines, evidence for the efficacy of intravitreal steroids, anti-VEGF, TNF-α inhibitors, sub-Tenon steroid injections, and intravitreal steroid implants is limited, and all selected studies had moderate to high risk of bias. At present, no definitive conclusions can be drawn about the clinical efficacy of these injectable drugs1).
In the PREMED 2 trial, subconjunctival triamcinolone 40 mg reduced macular thickness and volume at 6–12 weeks postoperatively, whereas intravitreal bevacizumab 1.25 mg showed no effect2).
The efficacy of “dropless cataract surgery,” which omits postoperative eye drops by administering subconjunctival or intracameral steroids during surgery, is being investigated, but whether it has equivalent safety and efficacy to conventional topical therapy is not established1). It may be an option for patients expected to have poor compliance.
The optimal treatment and duration for managing CME are not established1). Further validation is needed for NSAIDs, steroids, anti-VEGF, and combination therapies. Optimizing postoperative medication strategies according to the stage of diabetic retinopathy and determining the optimal dose of triamcinolone are also future challenges1).
