TENAYA and LUCERNE: Two-Year Results from the Phase 3 Neovascular Age-Related Macular Degeneration Trials of Faricimab with Treat-and-Extend Dosing in Year 2.

PURPOSE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A. DESIGN: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials. PARTICIPANTS: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older. METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen. MAIN OUTCOME MEASURES: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112. RESULTS: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112. CONCLUSIONS: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

COMPARISON OF RESOLUTION OF VITREOMACULAR TRACTION AFTER OCRIPLASMIN TREATMENT OR VITRECTOMY.

PURPOSE: To compare the functional and morphologic outcome of patients with vitreomacular traction (VMT) treated with either ocriplasmin treatment or vitrectomy. METHODS: Retrospective case series of patients treated with ocriplasmin or vitrectomy for VMT. OUTCOME MEASURES: resolution of VMT, change in outer retinal thickness, integrity of ellipsoid zone, subretinal fluid formation, and best-corrected visual acuity 2 weeks and 4 months after treatment. RESULTS: Fourteen eyes received ocriplasmin (Group 1). Vitreomacular traction resolved in 50% (Group 1a), and in 50%, it did not (Group 1b). Ten eyes underwent vitrectomy (Group 2). Vitreomacular traction resolved in 100%. Outer retinal thickness decreased significantly 2 weeks after treatment in Group 1 (P = 0.003) and in 1a (P = 0.018). Two weeks after treatment, Group 1a showed a disruption of the ellipsoid zone (P = 0.001) and subretinal fluid formation (P = 0.01) more often than 1b. Neither was observed 4 months after treatment. Best-corrected visual acuity decreased significantly in Groups 1 (P = 0.034) and 1a (P = 0.026). CONCLUSION: Most patients treated with ocriplasmin for VMT showed a transient reduction of best-corrected visual acuity, accumulation of subretinal fluid, and a loss of the ellipsoid zone after the resolution of VMT. Patients with surgical resolution of VMT did not show these findings. The advantage of a less-invasive intravitreal injection of ocriplasmin must be weighed against the lower success rate, the (transient) morphologic changes, and the uncertain visual benefit.

IMPACT OF LONG-TERM INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR ON PREEXISTING MICROSTRUCTURAL ALTERATIONS IN DIABETIC MACULAR EDEMA.

PURPOSE: Evaluation of the influence of long-term intravitreal anti-vascular endothelial growth factor treatment on preexisting retinal microstructural alterations in patients with diabetic macular edema. METHODS: Eyes with diabetic macular edema and a history of ≥ 20 intravitreal anti-vascular endothelial growth factor (aflibercept and/or ranibizumab) injections were included in this retrospective study. Primary outcome was the extent of disorganization of retinal inner layers, alterations at the outer plexiform layer/Henle fiber layer junction, disruption of external limiting membrane/ellipsoid zone, disruption of retinal pigment epithelium/Bruch complex, and retinal atrophy at baseline versus after ≥ 20 intravitreal injections as visualized by spectral-domain optical coherence tomography images. RESULTS: Of 383 eyes screened, 37 eyes were included in the current study. With the exception of outer plexiform layer/Henle fiber layer junction restoration, no significant changes regarding microstructural alterations between baseline and end of study were encountered after long-term anti-vascular endothelial growth factor (disorganization of retinal inner layers P = 0.381, outer plexiform layer/Henle fiber layer junction P = 0.001, external limiting membrane/ellipsoid zone P = 0.524, retinal pigment epithelium/Bruch complex P = 0.122, retinal atrophy P = 0.317). Best-corrected visual acuity significantly increased over the course of the study, corresponding to central retinal thickness and intraretinal fluid reduction (all P < 0.0001). The extent of microstructural alterations was negatively correlated with best-corrected visual acuity (P < 0.05). CONCLUSION: Apart from outer plexiform layer/Henle fiber layer junction layer restoration, no effect on preexisting retinal alterations was encountered after long-term intravitreal injections. Thus, intravitreal ranibizumab or aflibercept did not have a major effect (neither positive nor negative) on microstructural alterations.

[Functional and Anatomic Outcomes of Primary and Secondary Internal Limiting Membrane Transplantation in Large and Persistent Macular Holes]. / Funktionelle und anatomische Ergebnisse der primären und sekundären Internal-Limiting-Membrane-Transplantation zur Behandlung von großen und voroperierten Makulaforamina.

BACKGROUND: The gold standard therapy for full-thickness macular holes (FTMH) is vitrectomy (PPV) with peeling of the internal limiting membrane (ILM), gas tamponade of the vitreous cavity and postoperative face-down positioning. Nevertheless, eyes with large macular holes (> 400 µm) and surgical failures remain difficult to manage. Recently, ILM transplantation (ILM-TX) techniques were developed with acceptable results, advocating different mechanisms of hole closure: in such a setting, the ILM could serve as a scaffold for neuronal tissue in the pedicle ILM flap technique or the ILM could induce a contraction of the FTMH rims through shrinking of a folded ILM plug. PATIENTS/MATERIAL AND METHODS: This retrospective study evaluates the functional and anatomic outcomes following ILM-TX for large FTMH and failed FMTH surgery. Large holes (group 1) were treated by the pedicle flap and the plug technique. Persistent holes following vitrectomy and ILM peeling (group 2) were treated with the plug technique. All ILM-TX were performed under perfluorocarbon liquid (PFCL) with a subsequent silicone oil tamponade. RESULTS: In group 1 (6 eyes), three eyes had a free ILM graft and three eyes underwent a pedunculated ILM-TX. The mean best corrected visual acuity (BCVA, LogMar) before primary ILM-TX was 1.18 ± 0.54 with a mean initial hole size of 681 ± 106 µm and a photoreceptor defect (PRD) of 1829 ± 474 µm. Five of six eyes showed a postoperative anatomical macular hole closure (83%). The mean BCVA after a mean follow-up of 9.3 ± 5.1 months was 0.83 ± 0.31 after a free ILM graft and 0.95 ± 0.79 after a pedunculated ILM flap. The PRD reduced to 1781 ± 713 µm after a free ILM graft and 1148 ± 378 µm after a pedunculated ILM flap. In group 2 (7 eyes), all patients had failed initial macular hole surgery closure. Prior to free ILM-TX BCVA was 1.05 ± 0.41, the hole size was 433 ± 183 µm and PRD was 2012 ± 718 µm. After a mean of 9.6 ± 4.1 months following ILM-TX, in six of seven eyes the FTMH hole was closed (86%), BCVA improved to 0.53 ± 0.34 and the PRD shortened to 843 ± 291 µm. CONCLUSION: In most cases, with large FTMH or holes after failed vitrectomy plus ILM peeling, ILM-TX allows a hole closure. Functional outcomes show stabilization and sometimes even a slight improvement.

LOW ENDOPHTHALMITIS RATES AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS IN AN OPERATION ROOM: A Retrospective Multicenter Study.

PURPOSE: To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in three European hospitals performed in an operation room (OR) under sterile conditions. METHODS: A retrospective multicenter study between 2003 and 2016 at three European sites, City Hospital Triemli Zurich, Switzerland (CHT), Zealand University Hospital Roskilde, Denmark (ZUH) and University Clinic Bern, Switzerland (UCB). Intravitreal injection (IVI) database of each department was reviewed. All anti-vascular endothelial growth factor injections were performed using a standardized sterile technique in an operation room. Injection protocols were similar between the three sites. No preinjection antibiotics were given. Postoperative antibiotics varied among sites. RESULTS: A total of 134,701 intravitreal injections were performed at the 3 sites between 2003 and 2016. Ten cases of presumed endophthalmitis were documented: 4 in 50,721 at CHT (95% CI: 0.0071-0.0087%), 2 in 44,666 at ZUH (95% CI: 0.0039-0.0051%), and 4 in 39,314 at UCB (95% CI: 0.0092-0.011%). This results in one case in 13,470 intravitreal injections and a combined incidence of 0.0074% per injection (95% CI: 0.0070-0.0078%). Positive cultures were found in 4 out of 10 presumed endophthalmitis cases. CONCLUSION: The standardized sterile technique in an operation room with laminar airflow showed very low rates of endophthalmitis at three European sites.

Angio-OCT de la zona avascular foveal en ojos con oclusión venosa de la retina.

Objetivo: El objetivo del estudio comprendía visualizar y cuantificar las alteraciones patológicas de la zona avascular foveal (ZAF) mediante angio-OCT en ojos con oclusión venosa de la retina (OVR) en comparación con el ojo contralateral sano. Procedimientos: La angio-OCT se llevó a cabo mediante el sistema Avanti® RTVue 100 XR (Optovue Inc., Fremont, Calif., EE. UU.). Los bordes de la capa vascular superficial (CVS) se definieron como 3 µm por debajo de la membrana limitante interna y 15 µm por debajo de la capa plexiforme interna y, para la capa vascular profunda (CVP), como 15 y 70 µm por debajo de la membrana limitante interna y de la capa plexiforme interna, respectivamente. La longitud de la ZAF horizontal, vertical y máxima de la CVS y la CVP en cada ojo se midió de forma manual. Además, se midió el ángulo entre el diámetro máximo de la ZAF y el plano papilomacular. Resultados: La angio-OCT representó los defectos dentro de la vasculatura en el área perifoveal en ojos con oclusión de rama venosa de la retina (ORVR; n = 11) y con oclusión de la vena central de la retina (OVCR; n = 8). Esto resultó en un crecimiento del diámetro máximo de la ZAF en ojos con OVR (n = 19) en comparación con el ojo contralateral (n = 19; 921 ± 213 frente a 724 ± 145 µm; p = 0,008). Además, se observó una correlación significativa entre la mejor agudeza visual corregida (MAVC) y el diámetro máximo de la ZAF en la CVP (ρ de Spearman = -0,423, p < 0,01). Por último, en los ojos con OVR, el ángulo entre el plano papilomacular y el diámetro máximo de la ZAF se dio tan solo en el 21,05% (CVS) y en el 15,79% (CVP) de los casos a 0 ± 15 ó 90 ± 15°, respectivamente. En ojos sanos, estos ángulos (que supuestamente representan una configuración de la ZAF regular) fueron más prevalentes (CVS 68,42 frente a 21,05%, p = 0,003; CVP 73,68 frente a 15,79%, p < 0,001). Conclusiones: La angio-OCT muestra alteraciones morfológicas de la ZAF en ojos con OVCR y ORVR. La correlación del diámetro máximo de la ZAF con la MAVC indica que estas alteraciones resultan funcionalmente relevantes.

SAVE-AMD: Safety of VEGF Inhibitors in Age-Related Macular Degeneration.

OBJECTIVE: To determine whether intraocular treatment with vascular endothelial growth factor (VEGF) inhibitors change systemic endothelial function (EF) in patients with neovascular age-related macular degeneration (AMD). METHODS: In this prospective, randomized, 2-center, double-masked controlled interventional trial, patients with neovascular and dry AMD were enrolled. Eligible neovascular AMD patients received 2 intravitreal loading doses of either ranibizumab 0.5 mg or bevacizumab 1.25 mg at 4-week intervals and were subsequently followed every 4 weeks and treated according to a pro re nata regime for up to 1 year. Patients with dry AMD served as controls. The primary endpoint was the change in EF assessed by flow-mediated dilatation (FMD) after 2 months of treatment with VEGF inhibitors in patients with AMD compared to patients with dry AMD. FMD was assessed with B-mode high-resolution ultrasonography of the left brachial artery. RESULTS: 24 patients with neovascular AMD and 26 patients with dry ADM were included in the trial. Treatment with VEGF inhibitors did not significantly change FMD (from 4.7 ± 2.4 to 3.9 ± 1.9% after 8 weeks, p = 0.07, and to 5.1 ± 2.0% after 1 year; p = 0.93 vs. baseline, respectively). CONCLUSIONS: EF did not significantly differ between patients with neovascular AMD treated with intravitreal VEGF inhibition and patients with dry AMD.

Optical coherence tomography angiography of the foveal avascular zone in diabetic retinopathy.

PURPOSE: To analyze foveal avascular zone (FAZ) dimensions and symmetry in patients with diabetic retinopathy (DR) compared to healthy controls using optical coherence tomography angiography (OCT angiography). METHODS: OCT angiography was performed via an Avanti® RTVue 100 XR OCT system (Optovue, Inc., Fremont, CA, USA) in patients with diabetes mellitus (DM) and healthy adults. A frame centered on the fovea was used for FAZ measurements. The borders of the superficial vascular layer were defined as 3 µm below the internal limiting membrane (ILM) and 15 µm below the inner plexiform layer (IPL), and for the deep vascular layer as15 µm and 70 µm below the IPL, respectively. Angles of maximum FAZ diameter were measured in all eyes by two graders. RESULTS: In healthy eyes (N = 25), the FAZ surrounding vascular arcades were intact, showing a vertical or horizontal oval symmetrical formation with a maximum diameter usually on the horizontal or vertical axis. Diabetic eyes (N = 29) presented with disintegrity of the vascular arcades, resulting in an enlarged FAZ. In the superficial layer, the mean horizontal FAZ diameter was significantly larger in the DR group (753 µm ±272 µm) than in the control group (573 µm ±177 µm, p = 0.029). The difference was even more pronounced in the deep layer, with a mean value of 659 µm ±194 µm in the control group and 1009 µm ±342 µm in the DR group (p = 0.001). Furthermore, in the superficial layer, the angle of the maximum FAZ diameter was 0° (±15°) or 90° (±15°) in 72.0 % of healthy eyes. In eyes with DR, the angle was 0° (±15°) or 90° (±15°) in only 6.9 % of cases, due to the irregular configuration of the FAZ. CONCLUSIONS: OCT angiography is capable of imaging retinal vasculature without dye injection. Our data suggest that it can detect disintegrity of the vascular arcades surrounding the FAZ, thus differentiating DM from healthy eyes. Vascular abnormalities were more pronounced in the deep vascular layer.

SYSTEMIC INTERLEUKIN 1ß INHIBITION IN PROLIFERATIVE DIABETIC RETINOPATHY: A Prospective Open-Label Study Using Canakinumab.

PURPOSE: To evaluate the effect of systemic interleukin 1ß inhibition using canakinumab (Ilaris) on retinal neovascularizations in proliferative diabetic retinopathy. METHODS: Patients with proliferative diabetic retinopathy were enrolled in a prospective uncontrolled pilot study. Canakinumab (150 mg) was given 3 times subcutaneously. The primary end point was the change in the area of neovascularization from baseline to Week 24. Secondary end points were the change in retinal edema measured and best-corrected visual acuity (BCVA), as well as systemic safety evaluation, HbA1c, and systemic inflammatory parameters. RESULTS: Systemic canakinumab treatment was well tolerated. None of the 8 eyes showed progression of neovascularizations within 24 weeks. Their mean size remained unchanged comparing 0.60 mm at baseline with 0.62 mm at Week 24 (P = 0.944). Median BCVA remained stable with 80 ETDRS letters at baseline and 82 ETDRS letters at Week 24. A not statistically significant reduction in retinal edema was detectable for the foveal central subfield thickness (mean, 313-295 µm). Mean HbA1c improved significantly from 7.92% to 7.30% within the 24 weeks (P = 0.046). Systemic inflammatory parameters remained overall unchanged. CONCLUSION: Systemic canakinumab showed no change in neovascularizations in diabetic retinopathy. Promising effects were seen on diabetic macular edema.

Optical Coherence Tomography Angiography of the Foveal Avascular Zone in Retinal Vein Occlusion.

PURPOSE: The aim of the study was to visualize and to quantify pathological foveal avascular zone (FAZ) alterations through optical coherence tomography angiography (OCT-A) in eyes with retinal vein occlusion (RVO) in comparison to the unaffected fellow eyes. PROCEDURES: OCT-A was conducted with the Avanti® RTVue 100 XR system (Optovue Inc., Fremont, Calif., USA). The borders of the superficial vascular layer (SVL) were defined as 3 µm below the internal limiting membrane and 15 µm below the inner plexiform layer, and for the deep vascular layer (DVL) as 15 and 70 µm below the inner plexiform layer, respectively. The length of the horizontal, vertical and maximum FAZ was manually measured for the SVL and DVL in each eye. Additionally, the angle between the maximum FAZ diameter and the papillomacular plane was measured. RESULTS: OCT-A depicted defects within the perifoveal vasculature in eyes with branch retinal vein occlusion (BRVO; n = 11) and central retinal vein occlusion (CRVO; n = 8). These resulted in an enlargement of the maximum FAZ diameter in eyes with RVO (n = 19) in comparison to the healthy fellow eyes (n = 19; 921 ± 213 vs. 724 ± 145 µm; p = 0.008). Furthermore, a significant correlation was found between best-corrected visual acuity (BCVA) and the maximum FAZ diameter in the DVL (Spearman's x03C1; = -0.423, p < 0.01). Lastly, in the eyes with RVO, the angle between the papillomacular plane and the maximum FAZ diameter was only in 21.05% (SVL) and 15.79% (DVL) of the cases at 0 ± 15 or 90 ± 15°, respectively. In healthy eyes, these angles (which putatively represent a regular FAZ configuration) were more prevalent (SVL 68.42 vs. 21.05%, p = 0.003; DVL 73.68 vs. 15.79%, p < 0.001). CONCLUSION: OCT-A shows morphological alterations of the FAZ in eyes with CRVO and BRVO. The correlation of the maximum FAZ diameter with BCVA suggests that these alterations are functionally relevant.

TREAT-AND-EXTEND REGIMENS WITH ANTI-VEGF AGENTS IN RETINAL DISEASES: A Literature Review and Consensus Recommendations.

PURPOSE: A review of treat-and-extend regimens (TERs) with intravitreal anti-vascular endothelial growth factor agents in retinal diseases. METHODS: There is a lack of consensus on the definition and optimal application of TER in clinical practice. This article describes the supporting evidence and subsequent development of a generic algorithm for TER dosing with anti-vascular endothelial growth factor agents, considering factors such as criteria for extension. RESULTS: A TER algorithm was developed; TER is defined as an individualized proactive dosing regimen usually initiated by monthly injections until a maximal clinical response is observed (frequently determined by optical coherence tomography), followed by increasing intervals between injections (and evaluations) depending on disease activity. The TER regimen has emerged as an effective approach to tailoring the dosing regimen and for reducing treatment burden (visits and injections) compared with fixed monthly dosing or monthly visits with optical coherence tomography-guided regimens (as-needed or pro re nata). It is also considered a suitable approach in many retinal diseases managed with intravitreal anti-vascular endothelial growth factor therapy, given that all eyes differ in the need for repeat injections. CONCLUSION: It is hoped that this practical review and TER algorithm will be of benefit to health care professionals interested in the management of retinal diseases.

Clinical outcome after switching therapy from ranibizumab and/or bevacizumab to aflibercept in central retinal vein occlusion.

PURPOSE: After 48 months, unresolved macular edema secondary to central retinal vein occlusion (CRVO) is present in more than half of the patients treated with ranibizumab/bevacizumab. Switching therapy to aflibercept, a more recent vascular endothelial growth factor-A (VEGF-A) inhibitor, as well as VEGF-B and placental growth factor inhibitor, might improve the clinical outcome in patients with CRVO who respond insufficiently to ranibizumab/bevacizumab. METHODS: The presented study is a retrospective analysis of CRVO patients (n = 13) responding insufficiently to ranibizumab and/or bevacizumab (requiring treatment every 6 weeks or more frequently). Treatment in these patients was switched to aflibercept, which was administered based on a 'treat and extend' regime. The injection interval, relapse-free interval, central retinal thickness, central retinal volume, visual acuity, and intraocular pressure (IOP) were evaluated prior to switching to aflibercept and at month 6 and year 1 after switching therapy. RESULTS: From baseline to year 1 after switching therapy to aflibercept, the mean injection interval (primary end point) increased by 0.51 months (p = 0.023) and the relapse-free interval by 3.02 weeks (p = 0.003). The mean central retinal thickness decreased by 195.84 µm and the mean central retinal volume (6 mm diameter) by -1.81 mm3 (p = 0.007). Correspondingly, the mean ETDRS score increased from 66.15 at baseline to 76.54 letters at year 1 after switching therapy to aflibercept (+10.38 letters, p = 0.021). The IOP was not statistically significantly affected (-1.2 mm Hg, p = 0.196). CONCLUSION: Switching therapy from intravitreal ranibizumab/bevacizumab to aflibercept in insufficiently responding macular edema secondary to CRVO elongates the injection interval and the relapse-free interval and provides an improved anatomical as well as functional outcome.

Effect of aflibercept in insufficient responders to prior anti-VEGF therapy in neovascular AMD.

PURPOSE: Evaluation of three aflibercept injections at 4-week intervals in patients with neovascular AMD showing an "insufficient anatomic response" to prior anti-VEGF therapy with ranibizumab or bevacizumab. METHODS: The retrospective analysis included 96 eyes that had received at least three intravitreal 0.5 mg ranibizumab or 1.25 mg bevacizumab injections over a period of no more than 4 months prior to switching to aflibercept. In addition, the selected eyes had to have evidence of persisting or increasing sub- or intraretinal fluid, observed in optical coherence tomography (OCT). All patients received a loading dose of three intravitreal 2 mg aflibercept injections at 4-week intervals. Evaluation included central retinal thickness (CRT) and maximum pigment epithelium (PED) height measured by spectral domain OCT and best-corrected visual acuity (BCVA) prior to the switch of therapy and 4 weeks after the third aflibercept injection. RESULTS: A significant reduction of mean CRT (-39 µm; p < 0.001) and maximum PED height (-46 µm; p < 0.001) as found 4 weeks after the third aflibercept injection. Eighty-two out of 96 eyes (85 %) had a PED just prior to switching to aflibercept. There was an improvement in BCVA of 1.9 letters 4 weeks after the last aflibercept injection; the vision gain, however, did not reach statistical significance (p = 0.061). The further analysis did not show any correlation of the change in CRT, maximum PED, and BCVA with the number of prior anti-VEGF treatments. CONCLUSION: Retinal edema and PEDs regressed significantly after switching to aflibercept in patients insufficiently responding to prior therapy with ranibizumab or bevacizumab. No correlation could be found with regard to the number of prior treatments.

Incidence of presumed endophthalmitis after intravitreal injection performed in the operating room: a retrospective multicenter study.

PURPOSE: To evaluate the incidence of presumed endophthalmitis (EO) after intravitreal injection (IVI) of anti-vascular endothelial growth factor agents performed in the operating room. METHODS: Retrospective study at 2 Swiss eye hospitals between 2004 and 2012. Hospital records were used to identify patients treated with an IVI of an anti-vascular endothelial growth factor agent between 2004 and 2012 and those treated for EO, defined as any intraocular inflammation treated with intravitreal antibiotics. All IVIs were performed using standard sterile technique in a Swiss Class 1 operating room. No patient received preinjection topical antibiotics. Postinjection topical antibiotics were used only in one hospital. RESULTS: A total of 40,011 IVIs were performed at the 2 centers during the study period. Of the IVIs, ranibizumab was injected in 36,398 (91%), bevacizumab in 3,518 (9%), aflibercept in 89 (0.2%), and pegaptanib in 6 (<0.1%). Three cases of post-IVI presumed EO occurred, yielding a combined incidence of 0.0075% per injection (95% confidence interval: 0.0026-0.0220%) or 1 case per 13,337 IVIs. Two of the three cases of EO occurred in patients using post-IVI antibiotics. All three cases followed ranibizumab injection and were culture negative by anterior chamber tap or vitreous biopsy. CONCLUSION: The risk of EO after IVI performed under the sterile conditions of the operating room was very low.

Epiretinal membrane surgery outcome in eyes with abnormalities of the central bouquet.

BACKGROUND: Clinical studies have shown that epiretinal membranes (ERM) as well as abnormalities of the central foveal bouquet (CB) can be classified in different stages according to their morphological appearance. Furthermore, visual acuity correlates with the different stages of these features. The present study evaluated how these findings change after the surgical removal of the ERM and their impact on functional outcomes. METHODS: In this retrospective study eyes with ERM were evaluated by SD-OCT scans before and after pars plana vitrectomy (PPV) with macular ERM and internal limiting membrane (ILM) peeling. CB abnormalities were classified according to their morphological appearance from stage 0 (no abnormalities) to stage 3 (acquired vitelliform lesion). ERMs were classified ranging from stage 0 (absence of ERM) to stage 4 (ERM with significant anatomic disruption of macula). Changes in morphology were correlated with visual acuity before and after surgery. RESULTS: 151 eyes were included into the study. Before surgery 27.2% (n = 41) of eyes showed CB abnormalities with stage 1 being the most common (11.9%, n = 18). Before surgery ERM was seen in all patients. The most common form was stage 1 (28.5%, n = 43), followed by stage 3 (27.8%, n = 42) and 2 (25.2%, n = 38). Only 18.5% (n = 28) presented with stage 4 ERM. The mean BCVA was 0.42 (logMAR) before and increased to 0.19 (logMAR) 8 weeks after vitrectomy (95% CI 0.20-0.28; p < 0.001). Patients who suffered from CB abnormalities had less increase in BCVA than patients who had no evidence of CB (0.28 vs. 0.14 logMAR; p < 0.001). Of all the patients with CB abnormalities at baseline, 68% had lower CB grading after the surgery (n = 28; 95% CI; p < 0.001). All patients showed an improvement of their ERM grading, with 98.7% reaching stage 0 (n = 151 vs. n = 149; 95% CI; p < 0.001). CONCLUSIONS: The study indicates that the presence of CB abnormalities correlates with worse visual function. They are furthermore associated with worse visual outcomes after PPV with ERM and ILM peeling. These findings are valuable for deciding on PPV in patients with ERM.

Anti-VEGF therapies and blood pressure: more than meets the eye.

"Wet" (also called neovascular) age-related macular degeneration (AMD) is a chronic progressive disease characterized by leakage of fluid or blood from choroidal neovascularization. It remains the leading cause of blindness in the developed world. Vascular endothelial growth factor (VEGF), which plays a key role in the pathogenesis of retinal neovascularization and vessel leakage leading to central vision loss, has emerged as a potential target in the treatment of wet AMD. Importantly, large-scale clinical trials have demonstrated that intravitreal VEGF antagonism prevents vision loss and may even improve visual acuity in patients with neovascular AMD. Because VEGF and its downstream mediator nitric oxide have a well-established cardioprotective role, however, it can be argued that the beneficial effects of VEGF antagonism in the eye may come at the cost of adverse systemic effects, particularly myocardial infarction and stroke.

Two-year outcomes of intravitreal aflibercept in a Swiss routine treat and extend regimen for patients with neovascular age-related macular degeneration.

The aim of this observational study was to assess the use and outcome of intravitreal aflibercept in a treat and extend regimen in treatment-naïve neovascular AMD patients in routine practice. This both retrospective and prospective study was conducted in four larger Swiss retina clinics (ASTERIA study). The primary endpoint was the mean change in best-corrected visual acuity (BCVA) in ETDRS letters from baseline to 12 months. Between December 2017 and August 2018, 160 patients were included. For patients with available data, the mean change in BCVA was + 8.4 (± 14.4) letters at month 12 (n = 139) and + 5.0 (± 11.4) letters at month 24 (n = 95). A mean number of 8.3 (± 2.4) injections were administered within the first year and 5.4 (± 2.9) injections during the second year. On average, the observed treatment interval at month 12 was 63.3 (± 22.0) days and increased to 69.1 (± 28.6) days at month 24. For 37% of the patients, a treatment interval ≥ 12 weeks was attained at month 24. In conclusion,  intravitreal aflibercept in a Swiss real-life treat and extend regimen resulted in comparable anatomic and functional outcomes as were observed in the prospective registration trials of aflibercept for nAMD treatment.

Morphological Reconstitution and Persistent Changes After Intravitreal Ocriplasmin for Vitreomacular Traction and Macular Hole.

Purpose: To assess the long-term anatomical and functional findings in patients with symptomatic vitreomacular traction (VMT), with or without full thickness macular hole (FTMH), after eye treatment with intravitreal ocriplasmin injection (IOI). Methods: This longitudinal case series includes 51 eyes from 51 symptomatic patients with VMT (<800 µm) who received a single IOI (Jetrea® 0.125 mg); 21 cases with an FTMH (<400 µm) were included. Best-corrected visual acuity (BCVA) and optical coherence tomography findings were recorded before IOI, and 1 day to 24 months thereafter. Data are presented as mean ± standard deviation. Results: Mean adhesion size before injection was 345 ± 146 µm. In 34 eyes (67%), complete release of VMT was observed; whereas VMT persisted in 17 eyes (33%). The latter included 15 of the 21 eyes (71%) with FTMH, 15 of which underwent pars plana vitrectomy and inner limiting membrane peeling. BCVA improved from (logarithm of the minimal angle of resolution [logMAR]) 0.41 ± 0.03 before injection to 0.32 ± 0.03 after 1 month and 0.23 ± 0.05 after 6 months and remained stable thereafter (0.24 ± 0.06 after 24 months of follow-up). Forty-five percent of the eyes presented submacular deposits soon after IOI that were not functionally relevant; 61% completely resolved by 12 months. Except floaters that disappeared within 48 h, no other adverse events were reported during follow-up. Conclusions: Treatment with ocriplasmin in a real-life setting showed an overall efficacy of 67% in patients with symptomatic VMT, with better results evident in the absence of an FTMH (70% vs. 62% VMT release) and a visual gain for over 2 years.

Tunnelled versus straight intravitreal injection: intraocular pressure changes, vitreous reflux, and patient discomfort.

PURPOSE: To compare tunnelled scleral intravitreal injection with straight scleral intravitreal injection concerning short-term intraocular pressure (IOP) changes, occurrence and amount of vitreous reflux, and patient discomfort. METHODS: Sixty patients were randomly allocated to two groups (tunnelled intravitreal injection and straight intravitreal injection). IOP was measured before and directly (<1 minute) after the injection of 0.05 mL of an antivascular endothelial growth factor agent and then every 5 minutes until IOP was <30 mmHg. Occurrence and amount of vitreous reflux were recorded. Patient discomfort during injection was assessed with a Wong-Baker faces pain rating scale. RESULTS: IOP (mmHg +/- SD) increased significantly directly after injection to 35.97 +/- 8.13 (tunnelled intravitreal injection) and 30.19 +/- 12.14 (straight intravitreal injection). These pressure spikes differed significantly between both groups (P = 0.01, mean difference: -7.11). Five minutes after injection, there was no significant difference in IOP increase between the groups. All IOP measurements were <30 mmHg after 15 minutes. Occurrence and amount of vitreous reflux were significantly higher with straight intravitreal injection. There was no significant difference in Wong-Baker faces pain rating scale score between both groups. CONCLUSION: Tunnelled intravitreal injection seems to be the technique of choice for low-volume intravitreal injection (0.05 mL). There is neither a difference in patient discomfort nor a difference in IOP increase 5 minutes after injection between both groups. Significantly less vitreous reflux with tunnelled intravitreal injection should lead to less postinjectional drug loss.