Pseudophakic cystoid macular edema (PCME) is a condition in which fluid accumulates in the macula after cataract surgery, causing cystoid edema. It was first reported by Irvine in 1953, and later Gass described it in detail using fluorescein angiography, hence it is also called Irvine-Gass syndrome.
The incidence of clinical CME varies among studies 4). Including subclinical cases detected by OCT, the frequency is higher 5). It often occurs 4 to 12 weeks after surgery, and when accompanied by visual impairment, prompt diagnosis and treatment are required 2).
They essentially refer to the same condition. Irvine-Gass syndrome is a historical name, and it is modern practice to refer to cystoid macular edema after cataract surgery more broadly as PCME.
Suspect this disease when vision that once improved after surgery decreases again.
Slit-lamp microscopy may show no obvious abnormalities in the early stage, but characteristic findings are obtained by OCT and fluorescein angiography.
OCT Findings
Cystoid changes: Fluid accumulation from the outer plexiform layer to the inner nuclear layer. Petaloid cyst formation is characteristic.
Increased central retinal thickness (CST): Allows quantitative assessment and serves as an indicator of treatment efficacy. 2)
Subclinical type: Minor fluid accumulation without visual impairment is also detected by OCT.
FA Findings
Petaloid fluorescein leakage: Fluorescein angiography (FA) shows petaloid hyperfluorescence around the fovea in the late phase. A pattern specific to Irvine-Gass syndrome.
Optic disc leakage: May be accompanied by fluorescein leakage from the optic disc.
OCTA Findings
FAZ enlargement: Optical coherence tomography angiography (OCTA) may show enlargement of the foveal avascular zone (FAZ).
Capillary remodeling: In chronic cases, morphological changes in macular capillaries are observed.
The main cause of PCME is an increase in inflammatory mediators following cataract surgery, which is thought to lead to breakdown of the blood-retinal barrier (BRB)2, 5).
Major risk factors related to surgical technique and intraocular conditions are shown below.
| Risk Factor | Notes |
|---|---|
| Posterior capsule rupture/vitreous loss | Greatest intraoperative risk factor4) |
| Preoperative uveitis | Exacerbates inflammatory predisposition4) |
| Diabetic retinopathy | Underlying increased vascular permeability |
| Epiretinal membrane (ERM) complication | OR 4.535) |
| Prostaglandin analog eye drops | When used as glaucoma medication |
Regarding surgical procedures, a history of previous vitrectomy, retinal photocoagulation, and intraocular inflammation are also considered independent risk factors.
OCT (Optical Coherence Tomography) is central to diagnosis. It is non-invasive and highly sensitive, allowing quantitative assessment of fluid accumulation in the macula. 4) It evaluates cystoid changes in the outer plexiform and inner nuclear layers, the presence of subfoveal fluid, and central retinal thickness (CST).
Fluorescein angiography (FA) visualizes a petaloid pattern of fluorescein leakage, characteristic of PCME. It aids in differential diagnosis, but because it is invasive, OCT is preferred in routine practice.
OCTA is expected as a non-invasive alternative to FA for vascular assessment, providing information such as changes in the foveal avascular zone (FAZ) area.
There are multiple causes of cystoid macular edema, and differentiation from the following is important.
NSAID eye drops are the first-line treatment, suppressing prostaglandin production and improving CME 5). A 2024 meta-analysis showed that prophylactic NSAIDs reduced PCME risk (RR 0.33) 5).
Steroid eye drops are used for inflammation control, but for PCME prevention, NSAIDs alone or in combination have been widely studied 4, 5).
A stepwise treatment approach is shown below.
Step 1
NSAID eye drops: Nepafenac, bromfenac, etc. Start preoperatively and continue postoperatively.
Steroid eye drops: Used in combination with NSAIDs. The PREMED trial found NSAIDs + steroids effective. 4)
Step 2
Subtenon triamcinolone injection: Considered for refractory cases that do not improve with step 1 2).
Intravitreal anti-VEGF injection: Targets VEGF. An odds ratio of 0.151 indicates significant efficacy. 5)
Third stage
Ozurdex (dexamethasone intravitreal implant): A sustained-release steroid. Considered for refractory CME, but be cautious of increased intraocular pressure 2).
Vitrectomy (PPV): The last resort for refractory cases resistant to all drug therapies. 2)
Diabetic patients have a high risk of CME. For high-risk eyes, consider prophylactic administration combining NSAIDs and steroids before surgery 4, 5).
For PCME, first control inflammation with eye drops. If response is insufficient, consider local steroid injection, intravitreal treatment, or vitrectomy on a case-by-case basis 2).
For high-risk eyes, it is recommended to start before surgery. 4) Continue use after surgery and maintain until edema resolves. Be aware of recurrence after discontinuation, and determine the treatment duration according to the doctor’s instructions.
The main pathogenesis of PCME is the breakdown of the blood-retinal barrier (BRB) due to postoperative inflammation 2, 5).
Tissue damage from cataract surgery activates cyclooxygenase-2 (COX-2), leading to the production of prostaglandins (PG) via the arachidonic acid cascade. 2) PGs increase the permeability of BRB capillary endothelium, causing plasma components to accumulate in the outer plexiform layer and inner nuclear layer of the retina. This leads to the formation of cystoid structures.
VEGF also contributes to BRB breakdown, and the efficacy of anti-VEGF therapy supports this mechanism. 5)
Müller cells (retinal support glial cells) are also thought to be involved in maintaining fluid homeostasis. In cases where a macular hole closed spontaneously after CME resolved, it has been suggested that NSAID use may promote Müller cell regeneration and repair after CME resolution. 3)
da Costa DR et al. (BMC Ophthalmol 2022) reported a case of a 75-year-old woman with CME and a macular hole. 3) After CME resolved with NSAID eye drops, the macular hole closed spontaneously, and best-corrected visual acuity recovered to 20/25. The possibility of spontaneous closure due to promotion of Müller cell regeneration is discussed.
Ozurdex (dexamethasone 0.7 mg implant) is one option for refractory PCME, and further long-term efficacy and safety data are being accumulated 2).
Long-term sustained-release formulations such as fluocinolone acetonide implants are also accumulating data in refractory posterior segment inflammatory diseases. Their application to refractory PCME is under investigation 2).
The carbonic anhydrase inhibitor acetazolamide is sometimes used to treat CME, but the risk of serious side effects has been reported in elderly patients.
Kudasiewicz-Kardaszewska et al. (Life 2025) reported a case of an 87-year-old man who developed choroidal detachment after receiving acetazolamide 250 mg twice daily. 1) Although it improved within 8 days, a warning has been issued that local treatment should be prioritized over systemic acetazolamide in elderly patients.
Combination of CME and macular hole is rare, but cases have been reported where the macular hole closed spontaneously after CME resolved with NSAIDs. 3) This finding suggests that aggressive CME treatment may contribute to the restoration of macular morphology, supporting the importance of trying medical therapy before surgical intervention.
Ozurdex is considered for refractory CME that has resisted multiple drug therapies. Because of the risk of steroid-induced intraocular pressure elevation, careful consideration is needed in patients with glaucoma or high intraocular pressure. An ophthalmologist determines the appropriateness of administration.
