New clinical trial evidence guides treatment to CME in diabetics
There is a linear trend between the severity of diabetic retinopathy (DR) and the risk of developing clinically significant macular oedema (CSME) after cataract surgery, Rudy MMA Nuijts MD, PhD, told attending delegates the ESCRS/EURETINA Symposium, during the combined 18th EURETINA and 36th ESCRS Annual Conference in Vienna in September 2018.
“Pseudophakic cystoid macular oedema results from a postoperative inflammatory response and develops within 12 weeks after cataract surgery. It results from impaired blood-retina barrier function,” said Dr Nuijts, University Eye Clinic Maastricht UMC+, The Netherlands.
“A study showed that the relative risk of developing postoperative CME is 6.23 for patients with any degree of diabetic retinopathy (DR) and is 1.8 even for diabetic patients with no signs of DR,” he said.
However, proof of effective prophylaxis had remained elusive. In 2015, the American Academy of Ophthalmology stated that: “There is a lack of Level 1 evidence supporting the long-term visual benefit of NSAID therapy when applied solely or in combination with corticosteroid therapy.”
However, a report from the ASCRS Cataract Clinical Committee and the American Glaucoma Society stated: “The efficacy of NSAIDs is compelling, whether used alone, synergistically with steroids or for specific high-risk eyes.” Clearly, there was a need for irrefutable evidence.
The ESCRS-sponsored PREvention of Macular EDema after cataract surgery in non-diabetics (PREMED study report #1) introduced Level 1 evidence. This study was the first international, multi-centre, randomised controlled clinical trial directly comparing the efficacy of a topical NSAID, corticosteroid and the combination of both in the prevention of CSME.
In the PREMED study for non-diabetics, 914 patients were randomised to one of three treatment groups: topical NSAID (bromfenac), topical steroid (dexamethasone) and a combination of the two. CME was defined as the presence of cystic changes on OCT and an increase of central subfield mean macular thickness (CSMT) of ≥10% as compared to baseline. CSME was defined as the presence of CME and less than 0.2 logMAR improvement in corrected distance visual acuity as compared to baseline.
The study showed that mean postoperative CSMT and the incidence of CSME was lowest in patients who received both treatments, said Dr Nuijts. The incidence of CSME within 12 weeks postoperatively was 5.1% in the dexamethasone group, 3.6% in the bromfenac group and combination treatment reduced the incidence to merely 1.5% in non-diabetic patients.
PREMED study report #2 describes prophylaxis in diabetic patients. All patients received a combination therapy of topical bromfenac and dexamethasone and were randomised to receive no additional treatment; subconjunctival triamcinolone acetonide (TA); intravitreal bevacizumab; or the combination of both subconjunctival TA and bevacizumab. Mean postoperative CSMT was the main outcome of the study.
“Mean postoperative CSMT was lowest in patients who received TA prophylaxis, with 0.0% of patients having CSME within both six and 12 weeks after surgery,” said Dr Nuijts (see above).
There was a statistically significant increase in mean intraocular pressure (IOP) in these patients, however: +1.7mmHg at six weeks and +2.5mmHg at 12 weeks, with 7.1% of patients experiencing an IOP of ≥25mmHg.
“A single subconjunctival TA injection effectively prevents the development of CME after cataract surgery in diabetic patients. However, the risk of developing CME should be carefully weighed against the risk of developing an increased IOP.”
Intravitreal bevacizumab alone had no significant effect in preventing CME after cataract surgery, and there was no added benefit of bevacizumab when added to subconjunctival TA. This agrees with previous studies stating that intravitreal anti-VEGF injection did not decrease the incidence of CME at three and six months after cataract surgery in type 2 diabetic patients with stable non-proliferative DR.
What about DME in a patient scheduled for cataract surgery, and treatment of postoperative macular oedema if prophylaxis has failed to prevent it? Differentiating DME from postoperative pseudophakic CME (PCME) is crucial, he said. “Whereas both DME and PCME display a central macular oedema pattern, the oedema in DME is primarily located in the outer nuclear layer, without retinal nerve fiber layer thickening.”
The appearance of DME stands in contrast with PCME, in which subretinal fluid is more commonly seen. PCME is characterised by central and symmetric macular oedema, typically located in the central 1mm area of the macula. Central cystoid changes are confined to the inner nuclear layer.
Dr Nuijts also had several tips for treating macular oedema, based on the literature.
“Treat DME preoperatively with anti-VEGF injections, laser, steroids or a combination thereof prior to cataract surgery. Intravitreal anti-VEGF drugs and steroids can be combined with cataract surgery and are effective if DME is still present postoperatively. In patients without CME preoperatively, topical NSAIDs are effective, but additional oral NSAIDs (indomethacin), acetazolamide or sub-Tenon steroid injections do not improve the results.”
This research was carried out by Laura Wielders MD, PhD, on behalf of ESCRS PREMED Study Group
Rudy Nuijts: firstname.lastname@example.org