**20. Anti-VEGF medications as first choice**

Abundant published data emphasize the safety of all off-label and approved drugs. Ranibizumab (Lucentis®, Novartis, Basel, Switzerland) and Aflibercept (EYLEA®; Bayer HealthCare, Berlin, Germany/Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA) are preferable as initial treatment for eyes with DME and primary or secondary glaucoma, however the IOP needs close monitoring for spikes if larger volume has been injected intravitreally. This class of antibodies induces regression of the iris neovascularization and resolution of intraretinal edema and hemorrhages in eyes with PDR and this facilitates greatly the completion of PRP. An important consideration is the partial response and persistence of macular edema - data from Protocol T demonstrated chronic fluid in up to 65.9% of the eyes on bevacizumab, in 44.2% of the eyes on ranibizumab and

*High-Risk Diabetic Maculopathy: Features and Management DOI: http://dx.doi.org/10.5772/intechopen.99748*

39.2% of the eyes on aflibercept after 2 years of treatment [1]. The number of intravitreal injections during the first year is decisive – in Protocol T, after the loading dose, the eyes that ended up with chronic edema had on average 3 injection from the 24th to 52nd week vs. 6 injections in eyes without chronic DME for the same period. Even though the eyes with chronic edema were given 4 to 6 injections during the second year, they remained with persistent fluid, unlike the eyes without fluid after the first year – they maintained relative stability on 2–3 injections during the second year [1]. The ability of a high-risk patient to complete such an intensive treatment, particularly if the edema is bilateral, needs to be discussed beforehand.

### **21. Intravitreal dexamethasone as first choice**

The use of Dexamethasone intravitreal implant (0.7mg) (Ozurdex, Allergan, Inc., Irvine, CA, USA) in eyes with DME, alone or in combination with anti- VEGF drugs, vitrectomy and retinal laser has been studied extensively since 2011. The implant provides rapid resolution of the macular fluid in all compartments that is sustained oved the next 2–4 months. It decreases the existing hard exudates and prevents the formation of new ones [49], and reportedly reduces the rate of progression of retinopathy [50]. Dexamethasone implant is selected as primary treatment in patients with recent and severe cardiovascular complications or pregnancy where the risk of systemic side effects from anti-VEGF injections needs to be avoided. Severe chronic maculopathy is often refractory to anti-VEGF management and a trial loading dose with these drugs may turn out to be an unnecessary delay. A dexamethasone implant as initial treatment might be a better choice for such patients, moreover that treatment–naïve eyes consistently fared better that eyes on long previous non-steroidal management. The main concerns are the formation of cataract in phakic eyes and elevation in the IOP. In the MEAD studies, the incidence of cataract-related side effects was 67.9% in the 0.7mg dexamethasone implant and the rate of cataract surgery was 59.2%. In the same trial, an increase in IOP was observed in 27.7% of the eyes and 1.4% of them required a glaucoma procedure (trabeculoplasty, iridotomy, iridectomy, or trabeculectomy) [51]. A patient with advanced glaucoma, even well compensated on topical treatment or after glaucoma surgery, is at risk of developing further optic nerve disc damage and vision deterioration after a steroid- induced IOP spike. A short trial use of dexamethasone drops 4–5 times daily readily provokes a meaningful IOP elevation in a steroidal responder and foretells similar issues with the implant. In clinical practice, an increase in the IOP is observable a week after implantation and responds well to topical beta blockers and carbonic anhydrase inhibitors. The IOP needs monitoring for at least three months as in some cases it decreases after resolution of the implant, and in others it remains permanently high and requires consistent glaucoma care. The DME patients with glaucoma on intravitreal dexamethasone in our practice remained controlled on topical medications and none needed glaucoma surgery. The progression of cataract after several dexamethasone implants and the need for surgery as part of the vision rehabilitation has to be discussed with the high-risk patients beforehand - in most cases the possibility of good functional results outweigh the apprehension and fear (**Figures 4** and **6**). In vitrectomized eyes with aphakia, large iridectomies, zonulolysis, large peripheral defects in the posterior lens capsule and dislocated IOLs the implant tends to migrate in the anterior chamber and induce elevated IOP and corneal edema to a point that may require a corneal graft. A peribulbar depo-steroid might be a safer option in such complicated eyes.
