Time to Call into Question the Fundus-based Evaluation of Diabetic Retinopathy after Intravitreal Injections

This is an Editorial and does not have an abstract

Update on Management of Non-proliferative Diabetic Retinopathy without Diabetic Macular Edema; Is There a Paradigm Shift?

Diabetic retinopathy (DR) is the major cause of visual impairment and blindness in the working-age population. Conventional management for nonproliferative diabetic retinopathy (NPDR) without diabetic macular edema (DME) is derived from the findings of the Early Treatment Diabetic Retinopathy Study (ETDRS). Although the ETDRS protocol basically includes observation, selected cases of severe NPDR may undergo scatter laser photocoagulation. Post-hoc analysis of recent trials has shown that patients with NPDR receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) for DME would experience improvement in the DR severity scale (DRSS). In addition, recent randomized trials (PANORAMA and Protocol W) have revealed that early intervention with intravitreal aflibercept in eyes with moderately severe to severe NPDR is associated with significant improvement in DRSS and reduced vision-threatening complications of DR. Based on recent studies, it seems that the therapeutic approach to NPDR may undergo a substantial change and a paradigm shift toward considering early intervention with the administration of intravitreal anti-VEGF injections. However, the long-term results and the duration of adherence to anti-VEGF therapy for eyes with NPDR are not yet defined. It is also not apparent whether improvement in DRSS is a true disease modification. Studies showed that DRSS improvement is not associated with retinal reperfusion. In addition, DRCR.net Protocol W showed no visual acuity benefit with the early intravitreal aflibercept injection in moderate to severe NPDR as compared with performing observation plus intravitreal aflibercept applied only after progression to proliferative DR or vision-impairing DME. The cost–benefit ratio is also a challenge. Herein, we look at different aspects of early anti-VEGF application and discuss its pros and cons in the process of treating NPDR

Ranibizumab in retinal vein occlusion: Treatment recommendations by an expert panel

Retinal vein occlusion (RVO) is a common cause of retinal vascular disease, resulting in potentially irreversible loss of vision despite the existence of several therapeutic options. The humanised monoclonal antibody fragment ranibizumab binds to and inhibits vascular endothelial growth factor, a key driver of macular oedema in RVO. In 2010, ranibizumab was approved in the USA for the treatment of macular oedema in RVO and, in 2011, ranibizumab was approved in the European Union for the treatment of visual impairment caused by macular oedema secondary to RVO in branch and central RVO. Ranibizumab provides an additional therapeutic option for this complex disease: an option that was not fully considered during the preparation of current international guidelines. An expert panel was convened to critically evaluate the evidence for treatment with ranibizumab in patients with visual impairment caused by macular oedema secondary to RVO and to develop treatment recommendations, with the aim of assisting physicians to optimise patient treatment

Distinctive Mechanisms and Patterns of Exudative Versus Tractional Intraretinal Cystoid Spaces as Seen With Multimodal Imaging.

PurposeTo determine clear-cut distinctions between tractional and exudative intraretinal cystoid spaces subtypes.DesignRetrospective, multicenter, observational case series.MethodsA cohort of patients diagnosed with intraretinal cystoid spaces and imaged with optical coherence tomography (OCT), fluorescein angiography (FA), blue fundus autofluorescence (BFAF), en face OCT, and OCT angiography (OCT-A) was included in the study. All images were qualitatively and quantitatively evaluated.ResultsIn this study were included 72 eyes of 69 patients. Exudative intraretinal cystoid spaces (36/72 eyes, 50%) displayed a "petaloid" morphology as seen with en face OCT, FA, and BFAF. Tractional intraretinal cystoid spaces (24/72 eyes, 33.3%), displayed a radial "spoke-wheel" en face OCT pattern. There was no leakage with FA and BFAF did not reveal specific patterns. Eyes with full-thickness macular hole (FTMH, 12/72 eyes, 16.7%) displayed a "sunflower" en face OCT appearance. FTMH showed OCT, OCT-A, and BFAF features of both exudative and tractional cystoid spaces, but without any FA leakage. Inner nuclear layer (INL) thickness was significantly lower in tractional cystoid spaces (P < .001). There were a greater number of INL cystoid spaces in both the exudative and FTMH subgroups (P = .001). The surface area of INL cystoid spaces was significantly lower in the tractional subgroup (P < .001). There was a significant reduction of the microvascular density in eyes with exudative vs tractional (P = .002) and FTMH (P < .001) subgroups.ConclusionsExudative and tractional intraretinal cystoid spaces displayed characteristic multimodal imaging features and they may represent 2 different pathologic conditions with equally different clinical implications

Topical treatment of diabetic macular edema using dexamethasone ophthalmic suspension: A randomized, double-masked, vehicle-controlled study.

PURPOSE To evaluate topical dexamethasone ophthalmic suspension OCS-01 (Oculis SA, Lausanne, Switzerland) in diabetic macular edema (DME). METHODS This was a multicenter, double-masked, parallel-group, randomized, Phase 2 study. Patients aged 18-85 years with DME of 0. RESULTS Mean CMT showed a greater decrease from baseline with OCS-01 (N = 99) than vehicle (N = 45) at Week 12 (-53.6 vs -16.8 μm, p = 0.0115), with significant differences favouring OCS-01 from Weeks 2 to 12. OCS-01 was well-tolerated, and increased intraocular pressure was the most common adverse event. Mean change in ETDRS letter score from baseline to Week 12 met the p was +2.6 letters with topical OCS-01 and 1 letter with vehicle (p = 0.125). In a post-hoc analysis, there was a greater difference in patients with baseline BCVA ≤65 letters, the OCS-01 group improved 3.8 letters compared with 0.9 letters with vehicle. CONCLUSION Topical OCS-01 was significantly more effective than vehicle in improving central macular thickness in patients with DME. Visual improvement was better in eyes with lower baseline vision

Sustained Benefits of Ranibizumab with or without Laser in Branch Retinal Vein Occlusion: 24-Month Results of the BRIGHTER Study

Purpose To evaluate the long-term (24-month) efficacy and safety of ranibizumab 0.5 mg administered pro re nata (PRN) with or without laser using an individualized visual acuity (VA) stabilization criteria in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). Design Phase IIIb, open-label, randomized, active-controlled, 3-arm, multicenter study. Participants A total of 455 patients. Methods Patients were randomized (2:2:1) to ranibizumab 0.5 mg (n = 183), ranibizumab 0.5 mg with laser (n = 180), or laser (with optional ranibizumab 0.5 mg after month 6; n = 92). After initial 3 monthly injections, patients in the ranibizumab with or without laser arms received VA stabilization criteria-driven PRN treatment. Patients assigned to the laser arm received laser at the investigator's discretion. Main Outcome Measures Mean (and mean average) change in best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) from baseline to month 24, and safety over 24 months. Results A total of 380 patients (83.5%) completed the study. Ranibizumab with or without laser led to superior BCVA outcomes versus laser (monotherapy and combined with ranibizumab from month 6; 17.3/15.5 vs. 11.6 letters; P P P = 0.4259). A greater reduction in CSFT was seen with ranibizumab with or without laser versus laser monotherapy over 24 months from baseline (ranibizumab monotherapy −224.7 μm, ranibizumab with laser −248.9 μm, laser [monotherapy and combined with ranibizumab from month 6] −197.5 μm). Presence of macular ischemia did not affect BCVA outcome or treatment frequency. There were no reports of neovascular glaucoma or iris neovascularization. No new safety signals were identified. Conclusions The BRIGHTER study results confirmed the long-term efficacy and safety profile of PRN dosing driven by individualized VA stabilization criteria using ranibizumab 0.5 mg in patients with BRVO. Addition of laser did not lead to better functional outcomes or lower treatment need. The safety results were consistent with the well-established safety profile of ranibizumab

A consensus definition for lamellar macular hole

Background: A consensus on an optical coherence tomography (OCT) definition of lamellar macular hole (LMH) and similar conditions is needed. Methods: The panel reviewed relevant peer-reviewed literature to reach a consensus on LMH definition and to differentiate LMH from other similar conditions. Results: The panel reached a consensus on the definition of 3 clinical entities: LMH, epiretinal membrane (ERM) foveoschisis and macular pseudohole (MPH). LMH definition is based on 3 mandatory criteria and 3 optional anatomical features. The 3 mandatory criteria are the presence of irregular foveal contour, the presence of a foveal cavity with undermined edges, and the apparent loss of foveal tissue. Optional anatomical features include the presence of epiretinal proliferation, the presence of a foveal bump and the disruption of the ellipsoid line. ERM foveoschisis definition is based on 2 mandatory criteria: the presence of ERM and the presence of schisis at the level of Henle’s fiber layer. Three optional anatomical features can also be present: the presence of microcystoid spaces in the inner nuclear layer (INL), an increase of retinal thickness, and the presence of retinal wrinkling. MPH definition is based on 3 mandatory criteria and 2 optional anatomical features. Mandatory criteria include the presence of a foveal sparing ERM, the presence of a steepened foveal profile and an increased central retinal thickness. Optional anatomical features are the presence of microcystoid spaces in the INL and a normal retinal thickness. Conclusions: The use of the proposed definitions may provide uniform language for clinicians and future research

Optical coherence tomography-based consensus definition for lamellar macular hole.

BackgroundA consensus on an optical coherence tomography definition of lamellar macular hole (LMH) and similar conditions is needed.MethodsThe panel reviewed relevant peer-reviewed literature to reach an accord on LMH definition and to differentiate LMH from other similar conditions.ResultsThe panel reached a consensus on the definition of three clinical entities: LMH, epiretinal membrane (ERM) foveoschisis and macular pseudohole (MPH). LMH definition is based on three mandatory criteria and three optional anatomical features. The three mandatory criteria are the presence of irregular foveal contour, the presence of a foveal cavity with undermined edges and the apparent loss of foveal tissue. Optional anatomical features include the presence of epiretinal proliferation, the presence of a central foveal bump and the disruption of the ellipsoid zone. ERM foveoschisis definition is based on two mandatory criteria: the presence of ERM and the presence of schisis at the level of Henle's fibre layer. Three optional anatomical features can also be present: the presence of microcystoid spaces in the inner nuclear layer (INL), an increase of retinal thickness and the presence of retinal wrinkling. MPH definition is based on three mandatory criteria and two optional anatomical features. Mandatory criteria include the presence of a foveal sparing ERM, the presence of a steepened foveal profile and an increased central retinal thickness. Optional anatomical features are the presence of microcystoid spaces in the INL and a normal retinal thickness.ConclusionsThe use of the proposed definitions may provide uniform language for clinicians and future research