Pseudophakic Cystoid Macular Edema
Author: Ameen Marashi, MD
Documenting the age and visual loss is essential, which includes the onset, central scotoma, duration metamorphopsia, and photopsia along with detailed ocular history, including associated ophthalmic diseases such as glaucoma, uveitis , ocular inflammation, retinal vascular disease such as diabetic retinopathy , retinal vein occlusion, retinitis pigmentosa, etc..
The precise previous ocular treatments such as topical medications should be documented especially for antihypertensive eye drops as prostaglandin analogs and beta-blockers, or any topical medications contain benzalkonium chloride  which may increase the risk of pseudophakic cystoid macular edema (PCME), and surgical interventions such as pars plana vitrectomy, laser, or injections (intravitreal, sub-tenon, etc.) documenting medication such as AntiVEGF, steroids or other.
Detailed information about the undergone cataract surgery should be documented, such as date of surgery, and, if available or possible, a reported complication, and duration of surgery.
Family history, including previous eye diseases or visual loss along with a medical history of diabetes mellitus, systemic hypertension along with cardiovascular diseases, sleep apnea, coagulopathies, thrombotic disorders, etc.. is documented.
A list of ocular examination should set
1) Best-corrected visual acuity (BCVA), this is an essential step which can be performed by a trained optometrist or certified ophthalmologist to document the visual impairment. And this will help in the follow-up visits to assess the efficacy of the treatment.
2) A slit-lamp examination done with a thorough exam of clarity and regularity of the cornea along with corneal or limbal wound integrity to rule out the presence of vitreous incarceration; slit-lamp examination should include a full exam to rule out conjunctival abnormality such injection of conjunctival vessels should be documented. And any other inflammations of the conjunctiva or eyelids documented and managed before any treatment decision. Assessment of the anterior chamber is essential to rule out vitreous strands and retained nuclear fragments along with inflammatory cells and flare. Meticulous iris exam to rule out iris tissue damage or defects along with posterior synechia is crucial as the all mentioned finding may increase the risk of PCME. It is very important to document the presence and position of intraocular lens (IOL) along with integrity and clarity of the posterior capsular as the presence of posterior capsular rupture with vitreous loss is a high risk of developing PCME.
3) Intra Ocular Pressure (IOP) documentation is essential as high IOP is associated with post-surgical complications such as vitreous loss and retained nuclear fragments or patients with glaucoma history.
Note when high IOP spotted a corrected IOP documented after central corneal thickness measurement.
4) Gonioscopy before dilated eye exam is essential to document anterior chamber angle status (open or closed) and to rule out neovascularization on the angle, anterior synechia, and retained nuclear fragments, especially in cases of high IOP.
5) Anterior hyaloid examination with retro illumination using slit-lamp microscopy to rule out tobacco dust (pigmented cells) and differentiate it from blood and inflammatory cells.
6) Bilateral dilated fundus exam is an essential and detailed examination of the optic disc, macula, posterior pole, a mid-peripheral and peripheral retinal exam with specialized indirect wide-field lenses using slit-lamp biomicroscopy or indirect ophthalmoscopy:
A. The fundus exam shows the loss of foveal reflex with increased central macular thickness with the cystic formation in the form of honeycomb best appreciated with red-free light. However, another less common fundus finding should be ruled out, such as splinter shaped hemorrhages and optic disc edema.
B. Vitreomacular traction appears as taut glistering faintly translucent membrane presenting the residual vitreomacular adhesion while epiretinal membrane appears in early stages as cellophane maculopathy, which presented as semi translucent or opaque membrane may cause wrinkling with or without causing distortion of underlying retinal tissues.
C. Core and posterior cortical of the vitreous searching for pigmented, blood, and inflammatory cells along with the presence of the Weiss ring.
D. Posterior pole and peripheral retinal exams should rule out the presence of retained nuclear fragments or/and peripheral retinal breaks.
E. Fundus exam should rule out signs of diabetic retinopathy such as microaneurysms or/and intraretinal hemorrhage, hard exudates, and retinal vein occlusion such as dilated and tortuous retinal veins with attenuation of the retinal artery along with intraretinal and flamed shaped hemorrhages or other retina signs of ischemia such as neovascularization, severe hemorrhages, cotton wool spots, and venous beadings documented. Presence of Vitreous or pre-retinal hemorrhage documented as well.
F. The fundus exam should rule out signs of retinitis pigmentosa, such as bone speculate, attenuation of the retinal artery along with optic disc pallor.
Fundus images can document and follow up patients with PCME. Fundus images show central macular edema with loss of foveal reflex with cystic changes best shown in red-free images along with documenting the presence of optic disc edema and splinter shaped hemorrhages.
Fundus images can be convenient to document the presence of other retinal pathologies that contribute to PCME such as:
Retinal vascular changes, including microaneurysms, neovascularization, intraretinal microvascular abnormalities, or/and intraretinal hard exudates, cotton-wool spots, intraretinal dot-blot hemorrhages, pre retinal or vitreous hemorrhage secondary to diabetic retinopathy. The same principle applies for retinal vein occlusion, especially when there is retinal vein dilated and tortuous along with intraretinal or/and flamed shaped hemorrhages.
Signs of posterior uveitis such as vitritis, retinitis, choroiditis, or chorioretinitis with or without vasculitis, and the vitreomacular abnormalities are secondary to uveitis. However, in cases, of retinitis pigmentosa, there are bone spicule peripheral retinal pigmentations with retinal vascular attenuation and pale optic disc.
Fundus image can document the presence of vitreomacular abnormalities such as dragging retinal vessels, macular edema, and in cases of full-thickness retinal distortion, which is presented in advanced stages.
Optical Coherence Tomography (OCT)
OCT is an essential tool to determine the presence of macular edema and to assess treatment efficacy along with differentiating the PCME from other macular pathologies.
PCME is presented with increased central macular thickness with intraretinal cystic formation along with loss of foveal pit with or without subretinal fluids.
In addition to previous OCT features some cases of PCME are presented with vitreomacular abnormalities such as vitreomacular traction features non-complete detachment of the posterior cortical hyaloid in the perifoveal area with a plate-like attachment on the center of the fovea and oblique anterior-posterior traction or epiretinal membrane features hyperreflective band over the inner surface of the retina forming pegs from the inner retinal tissues forming hyporeflective pockets and corrugated inner retinal surface with multiple inner retinal attachments.
OCT is a very useful tool to differentiate other causes of cystoid macular edema, such as DME or macular edema related to retinal vein occlusion. DME may present non-clear or hyporeflective cystic formation with or without hyperreflective foci with underlying shadowing presenting hard exudates. Macular edema related to retinal vein occlusion presented with increased hyperreflectivity of inner retinal tissue.
OCT angiography in PCME shows disruption of deep capillary plexus and formation of cystic space while all retinal layer slab may show increased foveal avascular zone with decreased vascular density; OCTa is a useful tool to spot the sign of ischemia to rule out other retinal vascular diseases .
Fundus Fluorescein Angiography (FFA)
FFA is an essential tool to diagnose and differentiate PCME from other pathologies that can cause cystoid macular edema.
PCME features perifoveal capillary dilatation and leakage in the early stages and leaking dots in the center (or non-central) of the macula, forming central petaloid configuration with staining of the optic disc in late-stage. Thus, it can help to differentiate PCME from diabetic macular edema, which shows hyperfluorescent dots from microaneurysms and may show leak in later stages. Wherein cases of retinal vein occlusion angiogram may show delayed vein filling and collateral vessels with or without retinal areas of hypoperfusion.
Note that the physician should obtain signed consent explaining the rare complications of FFA, including death 1/200000, and FFA facility should have an emergency plan in situ .
Managing patients with pseudophakic cystoid macular edema
There are four medical treatment options, which are:
Topical non-steroidal anti-inflammatory (NSAIDs)
There are several types of topical NSAIDs, such as bromfenac 0.09%, diclofenac 0.1 %, and ketorolac 0.4%, four times where nepafenac 0.1% three times a day for six weeks.
Two main types of topical steroids are used prednisolone acetate 1.0% or dexamethasone 0.1% four times daily for two weeks
1)A solution such as Triamcinolone acetonide 4 mg/0.1 ml
2)Biodegradable inserts such as Dexamethasone intravitreal implant with efficacy for up to 4 months.
Although studies have demonstrated the effectiveness of intravitreal steroids for macular edema, there is an increase of intraocular pressure; nevertheless, intravitreal steroids may have transit effect and PCME may recur, and a repeated injection is needed.
Another fluocinolone acetonide non-biodegradable intravitreal implant is available may offer efficacy up to 36 months but with increased risk of inducing elevated IOP.
Other ways to deliver steroids
Suprachoroidal injection of triamcinolone acetonide acetonide
Posterior sub-tenon injection of steroids such as triamcinolone acetonide
Sub-tenon or subconjunctival injection of steroids such as injection of triamcinolone acetonide
Periocular injection of steroids such as triamcinolone acetonide .
VEGF Blockade agents
The commercially available VEGF blockade agents are AntiVEGF, such as Bevacizumab, which used off label & Ranibizumab and VEGF trap agents such as Aflibercept and Conbercept (Available in China).
The injection should be carried out in sterile conditions where the injection site is prepared by disinfecting the skin using povidone-iodine 10%.
After installing topical anesthesia, and the conjunctiva disinfected using povidone-iodine 4%.
The injection is carried out after placing sterile drape and lid speculum isolating eyelashes in the superior temporal quadrant injection site measured with calipers 3.5 mm from the limbus. A 30 gauge half-inch needle is used to inject triamcinolone or VEGF blockade agents. In contrast, the dexamethasone implant comes with a 23 gauge injector that needs to be inserted obliquely after conjunctival displacement then inserted vertically and then injected after that a cotton tip applicator is placed over the injection site to prevent reflux of fluid.
Pars plana vitrectomy (PPV)
PPV is indicated in cases of PCME presented with vitreomacular abnormalities, recalcitrant PCME, or complicated with retained nuclear fragments.
The PPV technique in eyes suffering from PCME is to induce posterior vitreous detachment and to remove epiretinal membrane with ILM peeling in cases presented with an epiretinal membrane; any retained nuclear fragments should be removed during PPV.
It is utilized in cases presented with vitreous strands in the anterior chamber with vitreous incarceration at the wound site, which will help to relieve vitreous traction .
Spontaneous resolution of PCME may occur within several months. Treatment initiated with a combination  of topical NSAIDs such as bromfenac 0.09% q.i.d. for six weeks and topical steroids such as dexamethasone 0.1 % q.i.d. for two weeks then BCVA and OCT repeated, if this fails to resolve PCME, then intravitreal steroids are indicated . Then PCME assessed with OCT within four weeks. If the PCME recurs, then repeat injection is needed if PCME failed to resolve within four weeks post the first injection.Then an intravitreal injection of Anti-VEGF indicated  and assessed with OCT four weeks post-injection.
In case all the above treatment failed , or in cases of PCME persisted for more than six months (chronic PCME), or/and PCME presented with vitreomacular abnormalities such as vitreomacular traction or epiretinal membrane, then PPV is indicated .
In cases of non-diabetic patients scheduled for cataract surgery a combination of topical NSAIDs such as bromfenac 0.09% b.i.d. for two days before surgery and then two weeks post-surgery and topical steroids such as dexamethasone 0.1 % q.i.d. for two days before surgery and one week's post-surgery may reduce the risk of developing PCME in uneventful phacoemulsification.
In diabetic patients, without diabetic macular edema or proliferative changes, the above-mentioned prophylactic treatment and subconjunctival triamcinolone at the end of surgery can lower the incidence of PCME post uneventful phacoemulsification .
In diabetic patients, with diabetic macular edema or proliferative changes, the cataract surgery is deferred until the resolution of DME and regressing the PDR. The up-mentioned prophylactic treatment for a diabetic patient is applied.
For other retinal disorders presented with cystoid macular edema pre cataract surgery, the management of macular edema is indicated before surgery and then a prophylactic with a combination of topical NSAIDs and steroids as mentioned above.
Flow chart summarizes the approach and management of pseudophakic cystoid macular edema
Follow up and prognosis
-When following up patients with PCME, assessing BCVA along with the slit-lamp examination and IOP is mandatory before fundus examination, which should be done after pupil dilatation; however, the assessment of PCME post-treatment should be done using OCT.
-Patients are instructed to do self-monitoring test using the Amsler grid and refer to their ophthalmologist in case of developing new visual symptoms
-PCME usually occurs within 12 weeks of post-cataract surgery with a peak incidence in 4 to 6 weeks.
-PCME has a favorable visual and anatomical prognosis post-treatment.
1. Belair ML, Kim SJ, Thorne JE, et al. Incidence of cystoid macular edema after cataract surgery in patients with and without uveitis using optical coherence tomography. Am J Ophthalmol 2009;148(1):128-135.
2. Rashid S, Young LH. Progression of diabetic retinopathy and maculopathy after phacoemulsification surgery. Int Ophthalmol Clin 2010;50(1):155-166.
3. Miyake K, Ibaraki N, Goto Y, et al. ESCRS Binkhorst lecture 2002: Pseudophakic preservative maculopathy. J Cataract Refract Surg 2003;29(9):1800-1810.
4. Sacconi R, Corbelli E, Carnevali A, et al. Optical coherence tomography angiography in pseudophakic cystoid macular oedema compared to diabetic macular oedema: qualitative and quantitative evaluation of retinal vasculature. Br J Ophthalmol. 2018 Dec;102(12):1684-1690.
5. Yannuzzi LA, Rohrer KT, Tindel LJ, et al. Fluorescein angiography complication survey. Ophthalmology 1986;93:611-7.
6. Randazzo A, Vinciguerra P. Chronic macular edema medical treatment in Irvine-Gass syndrome: case report. Eur J Ophthalmol 2010;20(2):462-465.
7. Steinert RF, Wasson PJ. Neodymium:YAG laser anterior vitreolysis for Irvine-Gass cystoid macular edema. J Cataract Refract Surg 1989;15(3):304-307.
8. Heier JS, Topping TM, Baumann W, et al. Ketorolac versus prednisolone versus combination therapy in the treatment of acute pseudophakic cystoid macular edema. Ophthalmology 2000;107(11):2034-2038;discussion 2039.
9. Benhamou N, Massin P, Haouchine B, Audren F, Tadayoni R, Gaudric A. Intravitreal triamcinolone for refractory pseudophakic macular edema. Am J Ophthalmol. 2003;135(2):246–249.
10. Falavarjani GK, Parvaresh MM, Modarres M, Hashemi M, Samiy N. Intravitreal bevacizumab for pseudophakic cystoid macular edema; a systematic review. J Ophthalmic Vis Res. 2012;7(3):235–239.
11. Loewenstein A, Zur D. Postsurgical cystoid macular edema. Dev Ophthalmol 2010;47:148-159.
12. Harbour JW, Smiddy WE, Rubsamen PE, Murray TG, Davis JL, Flynn HW., Jr Pars plana vitrectomy for chronic pseudophakic cystoid macular edema. Am J Ophthalmol. 1995;120(3):302–307
13. Wielders LHP1, Schouten JSAG2, Winkens B2, van den Biggelaar FJHM2, Veldhuizen CA2, Findl O2, Murta JCN2, Goslings WRO2, Tassignon MJ2, Joosse MV2, Henry YP2, Rulo AHF2, Güell JL2, Amon M2, Kohnen T2, Nuijts RMMA2; ESCRS PREMED Study Group2. European multicenter trial of the prevention of cystoid macular edema after cataract surgery in nondiabetics: ESCRS PREMED study report 1. J Cataract Refract Surg. 2018 Apr;44(4):429-439. doi: 10.1016/j.jcrs.2018.01.029.
14. Wielders LHP1, Schouten JSAG2, Winkens B2, van den Biggelaar FJHM2, Veldhuizen CA2, Findl O2, Murta JCN2, Goslings WRO2, Tassignon MJ2, Joosse MV2, Henry YP2, Rulo AHF2, Güell JL2, Amon M2, Kohnen T2, Nuijts RMMA2; ESCRS PREMED Study Group2. European multicenter trial of the prevention of cystoid macular edema after cataract surgery in nondiabetics: ESCRS PREMED study report 2 J Cataract Refract Surg. 2018 Jul;44(7):836-847. doi: 10.1016/j.jcrs.2018.05.015
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These guidelines were reviewed and updated in September 2020