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.

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.

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.

Optical Coherence Tomography Angiography (OCT-A) in a Patient with Occult Retinal Dysfunction.

Multimodal imaging techniques were performed in a patient with a newly emerged visual field defect; a missing retinal lesion on fundus examination made the diagnosis challenging but infrared imaging showed a larger area of retinal abnormality temporal to the fovea. Indocyanine green angiography (IA) showed late hypofluorescence and there was mild hyperautofluorescence which is known from acute zonal occult outer retinopathy (AZOOR). Despite normal fluorescein angiography (FA) results, a perfusion loss in the outer retinal layer was detected by OCT-A. Similar OCT-A findings were recently described in patients with acute macular neuroretinopathy (AMN). Methods. The methods included FA and IA, spectral domain optical coherence tomography (SD-OCT), near infrared imaging, and autofluorescence imaging (AF), as well as OCT-A. Patient. A 36-year-old patient who suffered from acute symptoms of photopsia and scotoma on her left eye. She had an influenza-like illness two weeks earlier. The scotoma could be verified by visual field testing. Results. The affected retinal zone showed mild fading of external limiting membrane (ELM) and a disorganisation of the ellipsoid zone (EZ) on SD-OCT. OCT-A revealed a large area of reduced perfusion in the outer retinal vascular layer. Conclusion. OCT-A can help to detect reduced capillary network in patients with visual field defects and no visible fundus changes. This case seems to have features of different occult retinal disorders such as AZOOR and AMN.

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.

Microvascular abnormalities secondary to radiation therapy in neovascular age-related macular degeneration: findings from the INTREPID clinical trial.

PURPOSE: To report the incidence and features of retinal microvascular abnormalities (MVAs) occurring secondary to stereotactic radiotherapy (SRT) in a randomised double-masked sham-controlled clinical trial at 21 European sites. METHODS: Two hundred and thirty participants with neovascular age-related macular degeneration (AMD) treated with at least three intravitreal antivascular endothelial growth factor (anti-VEGF) injections prior to enrolment, and demonstrating a continuing need for re-treatment. INTERVENTIONS: 16 Gy, 24 Gy or sham SRT. All three groups received pro re nata anti-VEGF injections if the lesion was judged to be active at review visits. Colour fundus images from baseline and 6 months and fluorescein angiograms from baseline and annual visits were graded for measures of morphological outcome and safety using a prespecified protocol with accompanying definitions to distinguish RT-related MVA from non-specific retinal vessel abnormalities that are known to occur in neovascular AMD. The main outcome measure was MVA detected by months 12, 24 and 36 after enrolment. RESULTS: The frequency of MVAs in the combined SRT arms was 0% in year 1, 13.1% in year 2 and 30.3% in year 3. The area of MVA was small and the mean change in visual acuity in year 2 was similar in a subset of SRT eyes with MVAs, versus those without MVAs. MVA was considered to have possibly contributed to vision loss in 2 of 18 cases with MVA in year 2, and 5 of 37 cases in year 3. CONCLUSION: Treatment with SRT is associated with development of subtle MVAs that have little or no impact on visual outcome. These findings can help clinicians recognise the retinal MVAs that occur in response to SRT.

Photodynamic therapy in combination with intravitreal ziv-aflibercept and aflibercept injection in patients with chronic or repeatedly recurrent acute central serous chorioretinopathy: a single-center retrospective study.

PURPOSE: The objective of the study was to assess the effect of off-label photodynamic therapy (PDT) in combination with intravitreal off-label ziv-aflibercept or off-label aflibercept injection in patients with chronic or repeatedly recurrent acute central serous chorioretinopathy (CSC). PATIENTS AND METHODS: Changes in best corrected visual acuity (BCVA) and subfoveal subretinal fluid (sSRF) and maximum subretinal fluid (mSRF) were retrospectively analyzed in a single-center cohort study of 17 patients (18 eyes) with persistent subretinal fluid for more than 3 months of duration of CSC. Treatment efficacy was measured between injection and PDT at 30±15 days, 90±15 days and 180±30 days after PDT. RESULTS: Significant reduction of sSRF and mSRF was shown after therapy with ziv-aflibercept and aflibercept combined with PDT (p<0.001). Course of BCVA showed non-significant improvement within 6 months (p=0.065). One case of allergic reaction after fluorescein angiography and one case of ophthalmic migraine after ziv-aflibercept injection were documented. One case of reversible vision loss occurred during 6 months after combination therapy. No other adverse events or side effects were reported. CONCLUSION: Combination therapy of ziv-aflibercept and aflibercept with PDT seems to be beneficial, even in cases of chronic or repeatedly recurrent acute CSC. This includes cases of CSC resistant to or recurrent after medical treatment, PDT alone or therapy with anti-vascular endothelial growth factor alone.

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.

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.

Long-Term Intravitreal Dexamethasone Treatment in Eyes with Pretreated Chronic Diabetic Macular Edema.

PURPOSE: The aim of this study is to assess the effect of repeated injections of dexamethasone implants in patients with persistent diabetic macular edema (DME) despite prior therapies. METHODS: This retrospective interventional study involved 47 DME-afflicted eyes, which were administered ≥2 intravitreal injections of dexamethasone. Group 1 (34 eyes) received a dexamethasone monotherapy, whereas group 2 (13 eyes) received a combination therapy with intravitreal antivascular endothelial growth factor as needed. The duration of dexamethasone effect until retreatment and the change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were defined as outcome measures. RESULTS: A total of 197 injections of dexamethasone were administered in group 1 and 52 in group 2 during a mean follow-up of 23 ± 10 and 24 ± 13 months, respectively. Mean time to reinjection was 4.6 ± 0.5 (group 1) and 5.3 ± 1.0 months (group 2; P = 0.17). Reinjection intervals did not shorten over time for up to 10 dexamethasone injections per eye in group 1 and BCVA improved from before 1 month after the first implantation, 7.0 letters (P = 0.04). In group 2, there was no significant improvement in BCVA at any time point. CRT decreased from 534 ± 208 and 529 ± 215 µm to 287 ± 115 and 371 ± 78 µm at 3 months and increased to 460 ± 186 µm and 547 ± 175 µm before reinjection (groups1 and 2, respectively). The maximal CRT before each implantation remained stable over time. CONCLUSIONS: In eyes with chronic DME that respond incompletely to prior therapy or require frequent reinjections, dexamethasone shows promising long-term anatomic and functional improvement. The absence of a treatment effect reduction over time argues against a relevant rebound phenomenon.

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.

Comparison of Progression Rate of Retinal Pigment Epithelium Loss in Patients with Neovascular Age-Related Macular Degeneration Treated with Ranibizumab and Aflibercept.

Purpose. Retinal pigment epithelium (RPE) loss in neovascular age-related macular degeneration (nAMD) seem to have a linear progression but might be influenced by the treatment. The purpose of the study is the comparison of RPE loss over three years in patients treated with intravitreal ranibizumab to patients who were switched to aflibercept. Methods. A retrospective analysis with 96 eyes switched to aflibercept was conducted. The progression rate of RPE loss was evaluated in patients who showed atrophy one year prior to switch (n = 17) or on switch date (n = 19). The RPE loss was evaluated by spectral domain optical coherence tomography (SD-OCT). Further, 22 eyes from patients treated with ranibizumab were compared. Results. The median yearly progression of RPE loss after square root transformation showed no significant difference in the year prior to switch compared to the year after switch (p = 0.854). In patients who received only ranibizumab, the median yearly progression of RPE loss was 0.15 mm/y, for aflibercept patients, 0.13 mm/y. This difference was not statistically significant (p = 0.172). Conclusions. There seems to be a linear progression rate of RPE loss in patients treated with ranibizumab as well as in patients with aflibercept. No significant increase of progression rate was found after switch to aflibercept.

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.

Aflibercept in branch retinal vein occlusion as second line therapy: clinical outcome 12 months after changing treatment from bevacizumab/ranibizumab-a pilot study.

PURPOSE: To evaluate the effect of aflibercept (as second line therapy) on the clinical outcome in patients with chronic macular edema secondary to branch retinal vein occlusion (BRVO) insufficiently responding to prior treatment with bevacizumab and/or ranibizumab. METHODS: Ten eyes of ten patients (n = 10) with chronic macular edema secondary to BRVO were included in a retrospective analysis. These patients received aflibercept after an insufficient response to treatment with ranibizumab and/- or bevacizumab. All intravitreal injections were administered according to a "treat and extend" regimen. Insufficient response was defined as the necessity of injection intervals of 6 weeks or less. The primary outcome of the study was the change in mean injection interval from baseline (prior switching to aflibercept) to month 12 after conversion to aflibercept. Secondary outcomes included the change in best corrected visual acuity (BCVA), central retinal thickness (CRT), central retinal volume (CRV) and intraocular pressure (IOP). RESULTS: All patients completed 12 months follow-up. In total, patients received a mean of 15.5 injections of ranibizumab and/or bevacizumab over a mean period of 23.1 months prior to switching to aflibercept. The primary endpoint indicated a significant increase in the injection interval from 5.0 weeks at baseline to 8.3 weeks at month 12 (p = 0.002). Secondary outcomes showed favorable results. Mean BCVA increased from 72.7 letters at baseline to 77.9 letters at month 12 after treatment initiation with aflibercept (+5.2 letters, p = 0.375). Correspondingly, CRT values decreased by 61.7 µm (p = 0.344) and the mean CRV (6 mm diameter) by 0.86 mm3 (p = 0.021) from baseline to 1 year after treatment initiation with aflibercept. During the treatment period with aflibercept no significant changes in intraocular pressure were registered (p = 0.238). CONCLUSIONS: Changing treatment to aflibercept in patients with chronic macular edema secondary to BRVO showed a statistically significant extension of the retreatment interval as well as beneficial anatomic changes in our study group. Our data do not allow a definite conclusion since the study was not controlled.

Assistive Device for Efficient Intravitreal Injections.

Intravitreal therapy is the most common treatment for many chronic ophthalmic diseases, such as age-related macular degeneration. Due to the increasing worldwide demand for intravitreal injections, there exists a need to render this medical procedure more time- and cost-efficient while increasing patient safety. The authors propose a medical assistive device that injects medication intravitreally. Compared to the manual intravitreal injection procedure, an automated device has the potential to increase safety for patients, decrease procedure times, allow for integrated data storage and documentation, and reduce costs for medical staff and expensive operating rooms. This work demonstrates the development of an assistive injection system that is coarsely positioned over the patient's head by the human operator, followed by automatic fine positioning and intravitreal injection through the pars plana. Several safety features, such as continuous eye tracking and iris recognition, have been implemented. The functioning system is demonstrated through ex vivo experiments with porcine eyes. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:752-762.].

Response of Postoperative and Chronic Uveitic Cystoid Macular Edema to a Dexamethasone-Based Intravitreal Implant (Ozurdex).

PURPOSE: To survey the clinical responses to treatment of chronic postoperative and uveitic cystoid macular edema (CME) with a dexamethasone-based intravitreal implant (Ozurdex(®)). METHODS: This retrospective, interventional case series reports on patients with chronic CME after uncomplicated vitrectomy for epiretinal gliosis or phacoemulsification (group 1: 12 eyes) or secondary to noninfectious endogenous uveitis (group 2: 36 eyes). Central retinal thickness (CRT), best-corrected visual acuity (BCVA, logMAR), and intraocular pressure (IOP) throughout follow-up were gleaned from the medical records. RESULTS: In group 1, CRT decreased, compared with baseline, from 519 ± 43 to 297 ± 23 and 356 ± 49 µm by the 1- and 3-month visit (P = 0.02) and to 429 ± 57 µm before reimplantation. In group 2, CRT decreased from 460 ± 31 to 300 ± 21 and 312 ± 26 µm by the 1- and 3-month follow-up, respectively (P = 0.001), and to 373 ± 32 µm before reimplantation. Complete resolution of CME was achieved in 67% and 94% (groups 1 and 2, respectively) by 1 month and in 42% and 80% by 3 months after injection. In group 1, BCVA improved from 0.46 ± 0.08 to 0.27 ± 0.09 and 0.20 ± 0.06 (P = 0.01) by the 1- and 3-month follow-up, respectively, and to 0.32 ± 0.08 before reimplantation. In group 2, BCVA improved from 0.47 ± 0.06 to 0.34 ± 0.09, 0.26 ± 0.07, and 0.29 ± 0.08 (P < 0.05) at 1 and 3 months of follow-up and before reimplantation, respectively. A significant IOP increase was not observed in either group. Mean time to reimplantation of Ozurdex was 6.4 ± 5.7 and 6.6 ± 3.4 months for postoperative and uveitic CME, respectively. CONCLUSION: Ozurdex seems to achieve a sustained effect over up to 6 months in postsurgical and uveitic CME.