Chronic cystoid macular edema (CME) following intraocular surgery is among the most frustrating postoperative complications for patients. A review of risk factors for CME found that approximately 1 in 400 cataract surgeries result in postoperative CME, and eyes with a history of uveitis or that have experienced intraoperative complications during surgery are more likely to develop postoperative CME.1,2

Retina and uveitis specialists are commonly tasked with addressing chronic postoperative CME, and it behooves us to know the latest innovations and management strategies. In this article, I provide an overview of CME’s real world presentation, discuss the pathophysiology of the condition, explore which factors drive treatment decisions, and review options for therapy. I also review 2 cases that illustrate the effects of prompt treatment.

There is no consensus definition of chronic postoperative CME. In broad terms, chronic postoperative CME occurs when there is evidence of persistent inflammation following intraocular surgery, for at least 6 consecutive months after surgery, and when continued therapy is required to keep such inflammation in check. Therapy includes topical, oral, and intra- or periocular corticosteroids, as well as steroid-sparing immunomodulatory agents.

When evaluating a case of suspected postoperative CME, retina specialists must exclude other entities that might present similarly. Postoperative chronic low-grade endophthalmitis (ie, Propionibacterium acnes endophthalmitis) can present similarly to chronic postoperative CME, and clinicians should look carefully for the presence of capsular plaques and may wish to run the relevant tests to rule out infection.

FDA approves XIPERE for treatment of macular edema associated with uveitis

The positioning of an IOL should be assessed to evaluate for uveitis-glaucoma-hyphema syndrome, which can also contribute to chronic postoperative CME. Anatomical variables such as epiretinal membranes, vitreomacular traction, and traction due to vitreous prolapse to the wound should be assessed. In older patients, there should also be an index of suspicion for masquerade syndromes, such as intraocular lymphoma. It is appropriate to perform a basic uveitis workup in eyes suspected to have chronic postoperative CME, as sometimes there may be an underlying, previously undiagnosed etiology for inflammation which was exacerbated following the intraocular surgery.

Short-term inflammation is inevitable following ocular surgery, and for most patients, the standard postoperative topical steroid taper is sufficient to address this inflammation within about a month. In addition to the risk factors outlined above (ie, surgical complications, history of uveitis), glaucoma surgery, longer surgical times, and diabetes place patients at risk for chronic postoperative CME and prolonged recovery.3,4

In patients with chronic postoperative CME, the course is often punctuated by periods of rebound inflammation throughout steroid taper. This chronic inflammation may lead to a persistently compromised blood-ocular barrier. By reestablishing the integrity of the blood-ocular barrier early in the course of CME, ocular immune privilege may be restored, which helps in sustained resolution of inflammation.

Prompt and adequate treatment of chronic CME is key to facilitating patients' recovery. Inadequate treatment, either via underdosing or inadequate duration of dosing, may lead to recurrent CME. This can result in long-term visual decline in a sawtooth pattern, with progressively reduced visual improvement at the zenith despite anatomical improvement, and increased declines at the nadir.5 Moreover, long-term changes to macular anatomy with chronic CME can be seen on OCT imaging, such as disorganization of the inner retinal layers and disruption of the outer retinal layers.6

Local steroid therapy with periocular or intraocular steroids is often the mainstay of treatment of chronic postoperative CME. Systemic immunomodulatory therapy (IMT) may be considered when there are concerns of steroid-induced IOP elevations which can be seen with local steroid delivery. It can also be useful in bilateral cases.

Earlier and more aggressive use of local corticosteroids may, in my experience, lead to reduced duration and severity of postsurgical CME. Some patients experience resolution after a single or a few injections (either intravitreal or sub-Tenon) of local steroids, whereas others require long-term, frequent dosing due to multiple recurrences. When eyes are steroid responsive but require more than 3 to 4 local steroid injections per year for sustained control, I consider the patient to be a candidate for a long-term steroid implant, as long as they have not experienced a steroid-induced IOP elevation.

In my practice, I leverage the fluocinolone acetonide intravitreal implant 0.18 mg (Yutiq, EyePoint Pharmaceuticals) for patients with chronic recurrent postoperative CME whose disease has demonstrated a prior response to steroids and whose IOP is well controlled. I rarely use the surgically placed fluocinolone acetonide intravitreal implant 0.59 mg (Retisert, Bausch + Lomb) in such eyes due to the higher rate of IOP elevation, which may require incisional glaucoma surgery, but it is a valuable tool when there is very severe postoperative inflammation. It is important to counsel patients that rare breakthrough episodes of inflammation may occur despite the placement of a sustained release implant, and that in such cases adjuvant treatment with intravitreal triamcinolone acetonide or the intravitreal dexamethasone implant 0.7 mg (Ozurdex, Allergan) is helpful.

In patients with chronic, recurrent steroid-responsive CME, a long-term steroid implant such as Yutiq allows a reduction in treatment burden and sustained improvement in visual function and long-term preservation of retinal anatomy. It also enables reduced amplitude of fluctuations in retinal thickness as well as an associated saw-tooth functional decline.

Grewal has no financial disclosures related to this content.

1. Patel C, Kim SJ, Chomsky A, Saboori M. Incidence and risk factors for chronic uveitis following cataract surgery. 

2013:21(2):130-134. doi:10.3109/09273948.2012.752013

2. Llop SM, Papaliodis GN. Cataract surgery complications in uveitis patients: a review article. 

2018;33(1):64-69. doi:10.1080/08820538.2017.1353815

3. Sobrin L, Pistilli M, Dreger K, et al; Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study Research Group. Factors predictive of remission of chronic anterior uveitis. 

2020;127(6):826-834. doi:10.1016/j.ophtha.2019.11.020

4. Yang J, Cai L, Sun Z, et al. Risk factors for and diagnosis of pseudophakic cystoid macular edema after cataract surgery in diabetic patients. 

 2017;43(2):207-214. doi:10.1016/j.jcrs.2016.11.047

5. Jabs DA. Immunosuppression for the uveitides. 

2018;125(2):193-202. doi:10.1016/j.ophtha.2017.08.007

6. Grewal DS, O’Sullivan ML, Kron M, Jaffe GJ. Association of disorganization of retinal inner layers with visual acuity in eyes with uveitic cystoid macular edema. 

2017;177:116-125. doi:10.1016/j.ajo.2017.02.017

Articles

Prompt and adequate action is a key to facilitating the best recovery in patients. 

Weighing treatments for chronic postop cystoid macular edema

Performing cataract surgery on very young children comes with several challenges, partly due to the anatomical peculiarities of an eye that may be just a few weeks old but mainly because the initial operation is usually just the first of numerous interventions that may be necessary over the next few years to give the patient a chance of developing normal, healthy vision. The femtosecond laser can play a crucial role in achieving this goal.

We were one of the first centers to employ the femtosecond laser in pediatric cataract cases, which is, as with many interventions in our youngest patients, an off-label procedure or contraindication for most laser platforms (the Ziemer laser system is the exception because it has a CE mark for laser cataract surgery in pediatric cases).

There are some things in pediatric cataract surgery that the surgeon must be aware of before planning the intervention. There will be soft eye tissues with a low scleral rigidity, and the operation—and often the pre- and postoperative examinations—will have to be performed under general anesthesia.

There likely will be a high degree of difficulty in calculating the appropriate IOL power (if IOL implantation is intended). Automated keratometry will be necessary, and another consideration is that posterior capsule opacification (PCO) may develop in a relatively short time after surgery. This complication is almost guaranteed to occur if the posterior capsule is left intact. Finally, the surgeon must be able to perform a vitrectomy.

Choosing the best possible time to operate on a newborn or a very young child always means weighing the risks and benefits. After early surgery, massive axial elongation and a substantial myopic shift can be expected.

Operating at a very young age increases the likelihood of the major postoperative complication of glaucoma. This and other postoperative complications occur at a much higher incidence when surgery takes place when a patient is younger than 4 weeks.

SMILE offers low enhancement rate after nomogram adjustment

A general recommendation might be—with necessary caution—that unilateral congenital cataract should be operated upon 4 to 6 weeks after birth and bilateral cataract done at 6 to 10 weeks after birth.1,2

We have used the femtosecond laser for pediatric cataract surgery for almost 10 years and our experience has generally been very positive.3 Unlike in cataract surgery in adults, we do not employ the laser for lens fragmentation (this is done by aspiration) but primarily to achieve a perfect capsulotomy—anterior as well as posterior—which is essential, and not only when primary IOL implantation is intended.

With anterior capsulotomy as a crucial step in the operation and for postoperative visual recovery, we were satisfied with even our first pediatric laser cataract surgery cases when we found an optimal circularity of femtosecond-laser–created anterior and posterior capsulotomies.4 As expected, the size of the capsulotomy initially did not turn out as planned because of the elasticity. There was considerable widening of the capsule opening immediately after laser treatment.

With experience, we found that, particularly in very young children, the capsulotomy diameter tends to turn out larger than planned. In a clinical series involving 22 eyes of 18 patients, we were able to develop the Bochum formula, which corrects for this aberration.5

A desired capsulotomy diameter can be achieved using the following formula:

A true bane of pediatric cataract surgery is the high incidence of PCO. A special surgical technique—more for the experienced surgeon than for the newcomer—has the potential to considerably reduce the chance of this complication developing.

First described by Marie-José Tassignon, MD, in 2002, during bag-in-the-lens (BIL) technique the anterior and posterior capsules are placed in a special IOL’s flange after creating both an anterior and a posterior capsulotomy with the femtosecond laser. The laser is particularly crucial for creating a perfectly centered posterior capsulotomy.

The IOL used is a foldable hydrophilic 1-piece IOL that is completely inserted and unfolded in the anterior chamber. Its posterior haptics are placed behind the posterior capsule and the anterior haptics are positioned in front of the anterior capsule. This prevents the proliferation and migration of lens epithelium cells over the long term and thus prevents PCO.

The femtosecond laser may make this manually challenging technique an option for surgeons who have not previously implanted BIL lenses. The femtosecond laser can safely perform the posterior capsulotomy and keep the anterior hyaloid membrane intact.6

For patients with special needs, there are additional preoperative considerations. For instance, patients with Down syndrome have a higher incidence of childhood cataract than the general population.

But as Saifee et al7 stated based on their experience, cataract extraction in pediatric patients with Down syndrome does not appear to have a higher rate of surgical complications than does cataract surgery in the general pediatric population. There is no reason to assume that laser cataract surgery in these patients might be less effective or less safe than in children without this condition.7

Patients with Marfan syndrome may need surgery of the lens even when they do not have a cataract. Their vision is often compromised by a subluxation of the lens that may render the visual axis aphakic by irregular astigmatism from the lens periphery and also occasionally from lens opacity.

Phaco power modulation boosts safety, efficacy in cataract surgery

Lens removal with capsule fixation and IOL implantation is a valuable strategy to address these problems. However, as in the younger patients with congenital cataract, challenges with manual capsulorhexis result from the high elasticity of the capsule (which has a tendency toward posterior tears), damage to the zonules from stress during manipulation, and the fact that the desired position for capsulorhexis is off center, all too often resulting in increased intraoperative complications for these patients who undergo surgery at a relatively young age.

In one of the first cases treated with a femtosecond laser, we operated on a 10-year-old boy with ectopia lentis in both eyes, employing the femtosecond laser in the right eye under general anesthesia. After the ocular surfaces were identified with the integrated algorithms, the capsulotomy was automatically placed by the software at the center of the scanned capsule, which was at the superior, temporal periphery of the pupil.

The selected capsulotomy diameter was 4.1 mm (incision depth: 1000 μm). No lens fragmentation was performed. The total suction time was 2 minutes and 45 seconds. A microforceps was used to remove the capsular disc, and no radial tears were noted. The soft lens was aspirated with standard bimanual irrigation/aspiration devices.

No complications were observed within 10 weeks of follow-up.8 Given the fact that pediatric laser cataract surgery for most laser platforms is off label, there are still shortcomings that hopefully will be overcome in the near future.

There is no software adapted for posterior capsulotomy, which makes it necessary to position the treatment zones manually. Only 2 laser platforms (Johnson + Johnson Vision and Ziemer) come with an interface for a smaller eye. There is no special formula for choosing the appropriate IOL for our youngest patients: all of them have been created for adults.

Experience has shown the Barrett formula to be more reliable than other formulas. It is worth noting that the ideal target refraction in very young infants seems to be a slight myopia as they primarily focus on near objects such as their toys or their mother’s face.9

The operation is the first step to visual recovery for a child with cataract, to be followed by long-term care provided by the ophthalmologist. The parents (or caregivers) must be educated about the need for continuous follow-up so that complications such as inflammation, glaucoma, and PCO can be detected and treated as soon as they arise, refractive errors can be corrected, and amblyopia therapy can be pursued.

For this first step, we should use all our expertise and the best technology available. In my view, this is—more often than not—the femtosecond laser.

Dick is professor and chairman at the University Eye Clinic of Ruhr University, Bochum, Germany. He is a consultant on demand for Johnson + Johnson.

1 Chang P, Lin L, Li Z, Wang L, Huang J, Zhao YE. Accuracy of 8 intraocular lens power calculation formulas in pediatric cataract patients. 

 2020;258(5):1123-1131. doi: 10.1007/s00417-020-04617-8

2 Self JE, Taylor R, Solebo AL, et al. Cataract management in children: a review of the literature and current practice across five large UK centres. 

. 2020;34(12):2197-2218. doi:10.1038/s41433-020-1115-6

3 Dick HB, Schultz T. Femtosecond laser-assisted cataract surgery in infants. 

. 2013;39(5):665-668. doi:10.1016/j.jcrs.2013.02.032

4 Gerste RD, Schultz T, Dick HB. Pediatric cataract surgery with the femtosecond laser. In: Dick HB, Gerste RD, Schultz T (eds.) 

Femtosecond Laser Surgery in Ophthalmology

5 Dick HB, Schelenz D, Schultz T. Femtosecond laser-assisted pediatric cataract surgery: Bochum formula. 

. 2015;41(4):821-826. doi:10.1016/j.jcrs.2014.08.032

6 Dick HB, Canto AP, Culbertson WW, Schultz T. Femtosecond laser–assisted technique for performing bag-in-the-lens intraocular lens implantation. 

. 2013;39(9):1286-1290. doi:10.1016/j.jcrs.2013.07.014

7 Saifee M, Kong L, Yen KG. Outcomes of cataract surgery in children with Down syndrome. 

. 2017;12(2):243-244. doi:10.4103/jovr.jovr_212_16

8 Schultz T, Ezeanosike E, Dick HB. Femtosecond laser-assisted cataract surgery in pediatric Marfan syndrome. 

. 2013;29(9):650-652. doi:10.3928/1081597X-20130819-06

9 Mohammadpour M, Shaabani A, Sahraian A, et al. Updates on managements of pediatric cataract. 

 2019;31(2):118-126. doi:10.1016/j.joco.2018.11.005

Performing cataract surgery on young patients can be a challenge, and the evolving technology can be used in cataract surgery for young children. 

Femtosecond laser boosts chances of pediatric patients developing normal vision

Bausch + Lomb and Clearside Biomedical recently announced the FDA granted approval of triamcinolone acetonide injectable suspension (Xipere) for suprachoroidal use for the treatment of macular edema associated with uveitis.

Formerly known as CLS-TA, the novel product represents the first treatment approved by the FDA for injection into the suprachoroidal space. 

The product is a proprietary preservative-free formulation of triamcinolone acetonide (TA), and the injection is performed as an in-office procedure using a proprietary syringe and needle platform (SCS Microinjector).

Study targets use of swept-source OCT to measure macular hole volume

The FDA approval was based on results of PEACHTREE (NCT02595398), a randomized, controlled, masked phase 3 clinical trial comparing treatment with 2 injections of suprachoroidal TA (weeks 0 and 12) or a sham procedure. 

PEACHTREE met its primary end point by showing statistical superiority of suprachoroidal TA vs sham for the percentage of eyes achieving a best-corrected visual acuity (BCVA) gain greater than or equal to 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline to week 24 (47% vs 16%, 

The study also met all secondary end points, including reduction in macular edema and improvement in anterior chamber and vitreous inflammation, and found the investigational corticosteroid was safe and well tolerated. 

Data from MAGNOLIA (NCT02952001), an extension study, showed the treatment benefit of suprachoroidal TA could persist for at least 9 months in many patients.

Steven Yeh, MD, is the first author of the published article reporting the PEACHTREE study and is a professor of ophthalmology at the Truhlsen Eye Institute, University of Nebraska Medical Center in Omaha.

“The approval of Xipere is an exciting advance in the care for patients with intraocular inflammation and macular edema associated with noninfectious uveitis,” he said. “Corticosteroids are a mainstay of treatment for this condition, and Xipere represents a new method of drug delivery that was well tolerated, showed good safety, and had striking benefit for improving visual acuity and other efficacy measures.”

Yeh pointed out that PEACHTREE assessed visual acuity is the primary end point. “This is an important point because of all the measurable clinical features of uveitic macular edema, vision is the one that most affects quality of life for our patients,” he said.

Yeh said the efficacy and safety of suprachoroidal TA may be understood by its pharmacokinetics, which show suprachoroidal delivery results in very compartmentalized distribution of the corticosteroid, targeting the pathology while limiting exposure to tissues that are adversely affected by corticosteroids. 

“Findings from preclinical studies show there is rapid dispersion of TA into the choroid and retina after suprachoroidal injection and persistence of high levels of the corticosteroid for more than 3 months. However, exposure of the anterior segment to the corticosteroid is limited,” he said. “Therefore, suprachoroidal TA offers the potential for rapid and effective control of uveitic macular edema with the potential to limit corticosteroid-related complications of cataract, IOP elevation, and glaucoma exacerbation.”


PEACHTREE randomized 160 patients 3:2 to treatment with triamcinolone 4 mg/0.1 mL or sham procedure. All anatomic subtypes of uveitis were represented in the study population.

Approximately 50% of patients in the suprachoroidal TA arm and two-thirds of controls were phakic. Mean time since uveitis diagnosis was 177 weeks in the suprachoroidal TA arm and 107 weeks in the control arm.

 Mean BCVA at baseline was approximately 55 letters in the suprachoroidal TA arm and 54 letters in the controls. Mean central subfield thickness (CST) in the 2 groups was 481 and 525 μm, respectively.

The secondary end point in PEACHTREE was mean change from baseline in CST measured by spectral domain optical coherence tomography at 24 weeks. 

Additional end points included mean change in BCVA in ETDRS letters by visit, mean change in CST by visit, and changes in signs of inflammation as evaluated by the Standardization of Uveitis Nomenclature scales. 

Mean reduction in CST from baseline to week 24 was significantly greater in the suprachoroidal TA arm than the sham group (153 vs 18 μm, 

Patients treated with suprachoroidal TA gained a mean of 9.6 ETDRS letters from baseline at week 4 and showed further improvement thereafter, reaching a mean gain of 13.8 ETDRS letters at week 24 compared with just 3.0 ETDRS letters in the control group (

Rescue therapy was allowed beginning at week 4 if patients met prespecified criteria or were not improving. It was received by 13.5% of patients in the suprachoroidal TA arm and 72% of control patients.

Tracking macrophages in the macular circulation with commercial OCT


Patients from PEACHTREE were eligible for participation in MAGNOLIA if they completed PEACHTREE without needing any rescue therapy. 

Of 46 patients originally randomized to suprachoroidal TA and 7 originally randomized to sham, 28 in the suprachoroidal TA group and 5 patients in the control group entered the extension study.

During the 24-week follow-up period in MAGNOLIA (48 weeks post randomization and 36 weeks after the second injection), 11 of the 28 patients originally treated with TA received rescue therapy, and 3 were withdrawn because of an adverse event. 

Thus, 14 of the 28 patients (50%) required no rescue therapy. Three of the 7 patients who had been in the PEACHTREE control arm received rescue therapy, and 2 others withdrew.

MAGNOLIA investigated median time to rescue treatment during the extension period as its primary end point and showed it was significantly longer in the triamcinolone group than in the control arm (257 days vs 55.5 days). 

At the end of the study, patients originally treated with suprachoroidal TA had a mean BCVA gain from baseline (PEACHTREE entry) of 12.1 ETDRS letters and a mean CST reduction of 174.5 μm.


No serious adverse events considered by the investigators to be related to treatment with suprachoroidal TA were recorded during PEACHTREE or MAGNOLIA. 

In PEACHTREE, the rate of elevated IOP pertaining to the corticosteroid (this analysis excludes events on the day of the procedure) was higher in the control group than in the triamcinolone arm (15.6% vs 11.5%), and the rate of cataract formation was only slightly higher in the triamcinolone group than among eyes receiving sham injection (7.3% vs 6.3%).

“It is important to note that in PEACHTREE, the suprachoroidal TA injection was well tolerated and associated with a lower rate of elevated IOP than the sham control procedure where rescue therapies could be administered during the trial,” Yeh said.


Yeh said all investigators participating in the premarketing clinical trials received special training for administering the injection. 

“The procedure used for suprachoroidal TA injection is a nuanced technique. However, it is very reproducible, can be learned by any ophthalmologist who is comfortable administering intraocular injections, and is well tolerated by patients,” he said.


Yeh is a consultant to Clearside Biomedical, Bausch + Lomb, Allergan, Regenxbio, Adverum Biotechnologies, and Buoy Health.

1. Khurana RN, Merrill P, Yeh S, et al. Extension study of the safety and efficacy of CLS-TA for treatment of macular oedema associated with non-infectious uveitis (MAGNOLIA). 

 2021;bjophthalmol-2020-317560. doi:10.1136/bjophthalmol-2020-317560

Triamcinolone acetonide injection approved for treatment of macular edema.

Ophthalmology Times: December 2021

Weighing treatments for chronic postop cystoid macular edema

Femtosecond laser boosts chances of pediatric patients developing normal vision

Therapy shows efficacy, durable benefit, favorable safety profile

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