**5. Diabetic retinopathy**

DR represents one of the leading causes of blindness among industrial countries with a worldwide prevalence of 34.6% (93 million people), becoming a relevant socioeconomic problem [26]. Therefore, research in this field is focused on both improving existing treatments and investigating new delivery systems. Several approaches to anti-VEGF therapy are currently being investigated, including sustained delivery, high-dose therapeutics, and a novel antibody biopolymer conjugate platform, in addition to exploring new treatments beyond anti-VEGF agents [27].

In the PANORAMA clinical trial, monthly injections of aflibercept (Eylea, Regeneron) were found to significantly reduce the occurrence of vision-threatening complication in both moderate severe and severe non-proliferative DR without center-involving diabetic macular edema (DME). The consequences related to proliferative DR, including vitreous hemorrhage and tractional retinal detachments, usually require surgical intervention [28].

Aflibercept is also being investigated in high-dose (8 mg) in PHOTON trial, which has demonstrated that, administered at intervals of 12 or 16 weeks, it provides noninferior BCVA compared to standard 2 mg aflibercept dosed every 8 weeks [29].

Moreover, a novel anti-VEGF, tarcocimab, is being investigated in phase 3 GLEAM and GLIMMER trial to evaluate the efficacy and safety of the intravitreal administration of 5 mg in the treatment of naïve DME in comparison with aflibercept [30, 31]. This new drug is a bioconjugate of a recombinant, full-length humanized anti-VEGF monoclonal antibody and a phosphorylcholine biopolymer.

Other potential intravitreal anti-VEGF therapies are currently in phase 2 and 3 trials including faricimab (Genentech/Roche), RC28-E (RemeGen), conbercept (Chengdu Kanghong Biotech), OPT-302 (Opthea), KSI-301 (Kodiak), and GB-102 (Graybug Vision). Furthermore, there are several novel targets in phase 2 trials: UBX1325, a senolytic Bcl-xL inhibitor, THR-149 (Oxurion), a bicyclic peptide that selectively inhibits human plasma kallikrein, and D-4517.2 (Ashvattha Therapeutics), a tyrosine kinase inhibitor. Many of these seem to offer increased durability or sustained release for the treatment of both DR and neovascular AMD [27].

On the other hand, the surgical treatment of DME has gained significant attention with the approval of the PDS with ranibizumab (Susvimo 100 mg/mL, Genentech/ Roche) in October 2021 [31]. The PDS is a permanent, refillable intraocular implant that is placed in the supero-temporal quadrant of the eye. The surgical technique consists of a 6 × 6 mm conjunctival peritomy and dissection, followed by scleral hemostasis, which allows for a full-thickness scleral incision of 3.5 mm in length, of 4 mm from the limbus. Laser is applied to the pars plana, which is then opened to release the SUVISMO implant. This PDS continuously releases ranibizumab over time and can be refilled in the office [32].

Two phase 3 randomized trials, PAGODA and PAVILION, evaluate the PDS with ranibizumab in the treatment of diabetic retinopathy in patients respectively with and without center-involving DME, respectively. Refill-exchange procedures occur every 24 and 36 weeks, respectively [33–35].

*Introductory Chapter: Treatment of Medical Retinal Diseases by Surgical Approaches… DOI: http://dx.doi.org/10.5772/intechopen.112174*
