An overview of the diagnosis and evidence-based management of one of the most common causes of visual acuity reduction following intraocular surgery.
Postoperative cystoid macular edema (PCME) is one of the most common causes of visual acuity (VA) reduction following intraocular surgery. It is characterized by the accumulation of intraretinal fluid resulting from the breakdown of the blood-retinal barrier.
Although it can occur after any intraocular surgery, it is most commonly associated with cataract surgery.1 Approximately 20% of patients who undergo uncomplicated phacoemulsification or extracapsular cataract extraction develop PCME; however, only 1% of these patients experience visually significant disease.2-4 When intraoperative complications such as posterior capsular rupture, vitreous prolapse, or iris trauma occur, the risk of symptomatic PCME rises to 20%.5 Most PCME cases resolve spontaneously within 3 to 12 months and go undiagnosed without requiring treatment.6
The pathogenesis of PCME is not completely understood. It is thought to involve increased intraocular inflammation following surgery, as well as mechanical factors such as vitreous traction.7 Elevated prostaglandin levels lead to upregulation of inflammatory mediators, which in turn stimulate increased production of VEGF.8 This cascade results in vasodilation and disruption of tight junctions within the perifoveal retinal capillaries.9 Breakdown of the blood-retinal barrier causes increased vascular permeability and subsequent accumulation of intraretinal fluid.10,11 This serous fluid tends to collect in the macula, primarily within the outer plexiform layer and inner nuclear layer.
PCME typically becomes clinically significant between 4 and 12 weeks following surgery. Patients may present with reduced VA, metamorphopsia, central scotoma, photophobia, ocular irritation, and redness.12 Diagnosis and assessment of PCME is accomplished through fundus examination and imaging modalities such as optical coherence tomography (OCT) and fundus fluorescein angiography (FFA).
In a normal retina, tight junctions of the retinal vasculature and retinal pigment epithelium prevent fluid from accumulating in the macula by blocking the passage of macromolecules into the extravascular space.13 Certain drugs, systemic conditions such as diabetes, ischemia, and mechanical forces can disrupt the blood-retinal barrier.
Several factors contribute to the development of PCME, including age, intraoperative complications, preexisting ocular pathologies, and systemic conditions (Table).14 Patients with preexisting diabetic macular edema (DME) may experience rapid worsening of their DME and a poor visual prognosis postoperatively. These patients should be treated prior to surgery or shortly thereafter if intraoperative fundus visualization is difficult due to the cataract.15,16 Similarly, patients with uveitis carry a significantly elevated risk of developing visually significant PCME postoperatively, with a reported incidence of 46%.17
IOL, intraocular lens; PCME, postoperative cystoid macular edema.
PCME can be classified into different forms depending on its severity and clinical significance. Angiographic PCME is the most common form and is often difficult to detect, as patients are frequently asymptomatic. It is identified through FFA, which reveals perifoveal capillary leakage. Clinically significant PCME presents with reduced VA, affecting patients' activities of daily living. When PCME persists for more than 6 months, it is considered chronic.25 Because of its persistent nature, chronic PCME can pose a significant therapeutic challenge for eye care providers.
It is essential to perform a thorough preoperative evaluation of risk factors to identify high-risk patients. This evaluation should include a comprehensive review of systemic and ocular medications, as well as the patient’s medical and ocular history. The use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced rates of PCME.26 Combined treatment with NSAIDs and corticosteroids has been shown to be more effective than either treatment alone.27 Additionally, it is highly recommended that patients with DME or proliferative retinal disease receive appropriate treatment prior to surgery to minimize postoperative complications.
Once PCME is identified, first-line treatment typically consists of topical corticosteroids and NSAIDs. Therapy may continue for several weeks to months to achieve complete resolution. Because of the prolonged duration of corticosteroid use, patients should be monitored closely for steroid response. If there is inadequate improvement with topical therapy alone, periocular or intravitreal corticosteroid injections may be initiated.28,29 In persistent or recurrent cases, dexamethasone implants may be used to provide sustained steroid release. Dexamethasone implant offers sustained release of dexamethasone for up to 6 months.30 For patients with refractory PCME, pars plana vitrectomy has been shown to significantly improve VA.31 Although evidence remains limited, oral acetazolamide has also demonstrated potential benefit in the treatment of PCME.32
Future therapeutic developments may further improve the management of PCME. One example is the OCS-01, a topical eye drop developed by Oculis that combines a higher concentration of dexamethasone with proprietary Optireach technology to ensure drug delivery to the retina. Though the DIAMOND phase 3 clinical trail in diabetic macular edema (DME) patients showed an improvement in retinal thickness on OCT, they failed to show a significant improvement in VA. Despite the setback in DME, the drug’s underlying steroid-based anti-inflammatory mechanism, which targets disruption of the blood-retina barrier, may still hold relevance for other indications, including PCME.33 As it currently stands, Oculis is not planning on pursuing FDA approval for OCS-01.
A 60-year-old woman presented for cataract consultation with no significant medical history reported at the time of evaluation. Her best corrected VA was 20/100 in the right eye (OD) and 20/25 in the left eye (OS). Ocular examination revealed moderate nonproliferative diabetic retinopathy (NPDR) with questionable mild macular edema OD and without macular edema OS, as well as mixed cataract significantly worse OS (Figure 1). Given the concern for underlying systemic disease, the patient was referred to her primary care provider for further evaluation. She was diagnosed with diabetes mellitus and was started on systemic treatment prior to cataract surgery. Following initiation of systemic therapy, the patient underwent an uncomplicated cataract extraction in the right eye. During the postoperative period, she required multiple adjustments to her diabetic medications due to adverse effects and suboptimal glycemic control.
Postoperatively, the patient reported good vision and comfort. Best corrected VA OD fluctuated between 20/30 and 20/20. At the 1-month postoperative follow-up, persistent cell and flare were noted in the right eye, prompting OCT imaging of the macula OD. OCT revealed mild cystic macular changes in the right eye (Figure 2). Given the subtle nature of the findings and the possibility that they may have predated the surgery, treatment was deferred, and the patient was scheduled to follow up in 2 weeks. At the follow-up, macular edema had significantly worsened, and treatment was initiated with prednisolone acetate 4 times daily and ketorolac 4 times daily in the right eye (Figure 3). The patient initially demonstrated further worsening before showing gradual improvement approximately 2 weeks after starting treatment (Figure 4). However, she developed an elevation in intraocular pressure secondary to steroid use, and dorzolamide-timolol twice daily OD was initiated. Despite treatment, macular edema continued to fluctuate (Figures 5-7). Prednisolone acetate was subsequently replaced with difluprednate 0.05% 4 times daily OD. Following this medication change, the patient demonstrated a robust response, with complete resolution of the macular edema within several weeks. Topical medications were then slowly tapered (Figures 8-9).
This case highlights several important considerations in the management of PCME. The patient’s preexisting NPDR, even if in the absence of macular edema, represented a significant risk factor for the development of PCME following cataract surgery. Furthermore, the concurrent challenges of newly diagnosed diabetes mellitus and suboptimal glycemic control likely contributed to the persistence and fluctuation of her macular edema.
The initial treatment with prednisolone acetate and ketorolac represents a standard first-line approach; however, this case illustrates that some patients may require a stronger steroid. The subsequent transition to difluprednate, a more potent topical corticosteroid with greater bioavailability, resulted in complete resolution of the edema, underscoring its potential role in in treating PCME. Resolution of PCME can take several weeks, so it is important to ensure proper expectations are established early in the treatment course. If the patient responds poorly to treatment or has persistent edema around the 3-month mark, referral for a retina consultation should be considered. Clinicians should remain vigilant for steroid response, as observed in this patient, and monitor and treat accordingly throughout the treatment course.
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