KESTREL and KITE Phase 3 Studies: 100-Week Results With Brolucizumab in Patients With Diabetic Macular Edema.

PURPOSE: To report the 100-week outcomes from the KESTREL and KITE trials. DESIGN: Two phase 3, double-masked, active-controlled, randomized trials. METHODS: Patients with diabetic macular edema (DME) were randomized 1:1:1 to brolucizumab 3 mg/6 mg (BRO3/BRO6) or aflibercept 2 mg (AFL) in KESTREL (N = 566) or 1:1 to BRO6 or AFL in KITE (N = 360). BRO3/BRO6 arms received 5 loading doses every 6 weeks (q6w) followed by q12w dosing, with an option to adjust to q8w at predefined disease activity assessment visits. In KITE, at week 72, based on the disease stability assessment, treatment intervals could be extended by 4 weeks in the BRO6 arm. AFL arms received 5 monthly loading doses followed by fixed q8w dosing. RESULTS: At week 100, change from baseline in BCVA (letters) was +8.8 for BRO6 and +10.6 for AFL in KESTREL; and +10.9 for BRO6 and +8.4 for AFL in KITE. In both studies, fewer BRO6 subjects had intraretinal fluid and/or subretinal fluid than AFL subjects. Results were achieved with 32.9% (KESTREL) and 47.5% (KITE) of BRO6 subjects maintained on q12w and q12w/q16w dosing, respectively. Intraocular inflammation rates for BRO6 vs AFL were 4.2% vs 1.1% (KESTREL) and 2.2% vs 1.7% (KITE), of which retinal vasculitis rates were 0.5% vs 0% in KESTREL, with no cases in KITE. Retinal vascular occlusion rates were 1.6% vs 0.5% (KESTREL) and 0.6% in both treatment arms in KITE. CONCLUSIONS: Results show the long-term efficacy and durability of brolucizumab in improving visual and anatomical outcomes in DME; the overall safety profile of brolucizumab remained unchanged through year 2.

See clearer: survey on the subjective and objective information levels as well as perception and information transfer using virtual reality headsets in patients with diabetic macular edema receiving anti-VEGF treatment.

PURPOSE: The purpose of this study is to investigate the use of a VR Headset in routine clinical practice as an additional source of information for patients with diabetic macular edema (DME) and their companions. METHODS: Survey including 121 patients with DME, 22 companions, and 14 healthcare professionals from 8 ophthalmology centers in Germany. Patients' and their companions' health literacy was assessed by questionnaires including knowledge statements before and after watching a VR-based 3-D educational video. HCPs' perspectives on the usability of a VR Headset were also assessed. RESULTS: Patients' mean age was 63.4 ± 12.2 years, 64.5% were men, and 76% (92/121) had previous anti-VEGF (VEGF, vascular endothelial growth factor) injections. After using the VR Headset, over 85% of patients and companions felt better informed about DME and its treatment. Patients' mean (± SD) number of correct answers to knowledge statements increased from 13.2 ± 3.7 before to 15.5 ± 2.3 after using the VR Headset. Over 95% of patients and companions rated content and ease of understanding of the video as "very good" or "good." Most patients and all companions considered the use of a VR Headset as a positive experience, most wishing to obtain information via VR Headset in the future. Most physicians and all medical assistants rated the effect of the VR Headset on patient satisfaction as positive and suggested further VR modules. CONCLUSION: After using the VR Headset, patients with DME and their companions demonstrated knowledge gains that may be meaningful individually and contribute to better adherence. This may offer an additional opportunity for knowledge transfer.

Main Principles of Vitrectomy Using Intraocular Tamponades - A Basic Course in Surgery. / Grundlagen der Vitrektomie unter Verwendung intraokularer Tamponaden ­ ein chirurgischer Basiskurs.

This article is intended to clearly present the basic principles for the use of intraocular tamponades in vitreous/retinal surgery in the event of retinal detachment and other pathologies using additional video footage. It examines the various gases, silicone oils and perfluorocarbon liquids with their indications, administration and in particular intraoperative handling including pitfalls and complications. Characteristic animations show the principles of use in surgery in a comprehensible way. The two lead authors dedicate this article to their teacher Prof. Dr. V.-P. Gabel, who in the early 1990s successfully established the first vitrectomy courses for ophthalmologists at Regensburg University Eye Clinic each year. Many colleagues who still work in retinal surgery today first started learning about this segment on these courses. The other coauthors participated under his supervision in annual vitrectomy wet labs run by the German Academy of Ophthalmology.

Retinal Vascular Occlusion after COVID-19 Vaccination: More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study.

BACKGROUND: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD). METHODS: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June-31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case-control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted. RESULTS: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA-1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our case-control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60-1.45, p = 0.75) in connection with a vaccination within a 4-week window. CONCLUSIONS: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk.

[Avoiding mistakes in anti-VEGF intravitreal injection therapy]. / Indikationen zur intravitrealen Injektionstherapie mit Anti-VEGF für Makulaerkrankungen ­ Fehler vermeiden.

Intravitreal injection (IVI) of drugs for treatment of various macular diseases is now one of the most frequently performed surgical procedures worldwide. As mostly chronic diseases are treated, the indications for treatment often mean a continuous treatment over years with a corresponding effort regarding spatial, personnel and financial resources. The diagnosis and indications for treatment are nowadays mainly made by spectral domain optical coherence tomography (SD-OCT). The ability to clinically assess and evaluate a fluorescence angiography is less practiced, although these are still a component of the indications for intravitreal injections. Therefore, it can happen that despite all diligence patients may receive anti-vascular endothelial growth factor (VEGF) treatment, sometimes permanently, based on a misinterpretation of the macular diagnosis or disease activity and these indications, once made, are rarely questioned or retracted. Therefore, the aim of this manuscript is to point out possible and typical misinterpretations in the indications or continuation of IVI treatment with anti-VEGF by means of case studies and to sensitize for differential diagnoses.

Rapid Isolation of Functional ex vivo Human Skin Tissue-Resident Memory T Lymphocytes.

Studies in animal models have shown that skin tissue-resident memory T (TRM) cells provide enhanced and immediate effector function at the site of infection. However, analyses of skin TRM cells in humans have been hindered by the lack of an optimized isolation protocol. Here, we present a combinatorial strategy-the 6-h collagenase IV digestion and gentle tissue dissociation - for rapid and efficient isolation of skin TRM cells with skin tissue-specific immune features. In comparison with paired blood circulating memory T cells, these ex vivo isolated skin T cells express typical TRM cell markers and display higher polyfunctional properties. Moreover, these isolated cells can also be assessed for longer periods of time in ex vivo cultures. Thus, the optimized isolation protocol provides a valuable tool for further understanding of human skin TRM cells, especially for direct comparison with peripheral blood T cells at the same sample collection time.

PERSEUS 24-month analysis: a prospective non-interventional study to assess the effectiveness of intravitreal aflibercept in routine clinical practice in Germany in patients with neovascular age-related macular degeneration.

PURPOSE: To evaluate the real-world effectiveness of intravitreal aflibercept injections in Germany in patients with neovascular age-related macular degeneration over 24 months. METHODS: PERSEUS was a prospective, non-interventional cohort study. The primary endpoint was the mean change in visual acuity (VA) from baseline. Secondary endpoints included the proportion of patients with a VA gain or loss of ≥ 15 letters and the frequency of injections and examinations. Patients with regular (bimonthly after 3 monthly injections during year 1 and ≥ 4 injections in year 2) and irregular (any other) treatment were analyzed. The last observation carried forward (LOCF) and the observed cases (OC) approach was applied for primary endpoint analysis to account for missing data. RESULTS: 803 patients were considered for effectivity analysis. At month 24, only 38% of the patients were still under observation. The LOCF population included 727, the OC population 279 patients. Treatment-naïve patients improved by 6.3 (LOCF)/8.1 (OC) letters with regular treatment over 24 months but only by 3.3 (LOCF)/3.1 (OC) letters with irregular treatment. The proportion of treatment-naïve patients achieving a VA improvement of ≥ 15 letters was similar between regularly and irregularly treated cohorts. However, considerably more patients in the irregular cohorts experienced a VA worsening of ≥ 15 letters than in the regular cohorts (LOCF: 18.7% vs. 7.4%). CONCLUSIONS: Regular IVT-AFL treatment resulted in better VA outcomes than irregular treatment at month 24. However, only a minority of patients received regular treatment over a 2-year period.

OCRIPLASMIN FOR VITREOMACULAR TRACTION IN CLINICAL PRACTICE: The INJECT Study.

PURPOSE: Randomized clinical trials have demonstrated the safety and efficacy of ocriplasmin in patients with vitreomacular traction (VMT), including those with macular hole (MH). The INJECT study prospectively evaluated ocriplasmin in the setting of clinical practice. METHODS: INJECT was a Phase 4, multicenter, prospective observational study. Patients were followed up for 12 months. Assessments included nonsurgical VMT resolution, nonsurgical MH closure, best-corrected visual acuity, occurrence of vitrectomy, and adverse events. RESULTS: The efficacy population (N = 395) received an ocriplasmin injection and had optical coherence tomography-confirmed VMT at baseline. At Day 28, the rate of nonsurgical VMT resolution was 40.7% in the overall group, and the rate of nonsurgical MH closure was 36.0% in the VMT with MH group. At Month 12, the rate of ≥2-line best-corrected visual acuity gain (irrespective of vitrectomy) was 36.8% in the overall group and 59.6% in the VMT with MH group. The percentage of patients who underwent vitrectomy in the study eye was 29.1% in the overall group and 55.6% in the VMT with MH group. Photopsia (9.8%) and vitreous floaters (6.8%) were the most frequent adverse events. CONCLUSION: The INJECT study showed that ocriplasmin is effective in a clinical setting in patients with VMT, with or without MH. No new safety signals were identified from this large and surgeon-selected patient group, although the significant limitations of the study design without an image reading center and scheduled study visit timings should be noted.

Importance of continuous treatment with intravitreal aflibercept injections in patients with neovascular age-related macular degeneration-12-month post hoc analysis of the PERSEUS real-world evidence study.

PURPOSE: To investigate the influence of treatment regularity with intravitreal aflibercept injections (IVT-AFL injections) on visual acuity (VA) outcomes in patients with neovascular age-related macular degeneration (nAMD) enrolled in the PERSEUS trial who received at least 7 IVT-AFL injections during the first year. METHODS: This was a post hoc analysis of the PERSEUS trial, a prospective, non-interventional, multicenter cohort study, and included 370 patients with nAMD who had received ≥ 7 IVT-AFL injections during year 1. In addition to the prespecified subgroups of treatment-naïve and previously treated patients, results were compared between patients with regular (n = 209) and irregular (n = 161) treatment. Regular treatment was defined as initial dosing with monthly IVT-AFL injections for 3 months, then bimonthly IVT-AFL injections until month 12. Irregular treatment was defined as any deviation from regular treatment (provided ≥ 7 injections were received). The outcome of primary interest was the mean change in VA from baseline after 12 months. Further outcomes of interest included VA gain or loss, proportion of patients achieving reading vision, and percentage of patients with fluid. RESULTS: At month 12, the mean (± standard deviation, SD) VA improvement from baseline was 6.1 ± 15.6 Early Treatment Diabetic Retinopathy Study letters in the regular cohort and 2.5 ± 16.7 letters in the irregular cohort with ≥ 7 IVT-AFL injections (P = 0.0514). Best results were obtained in the treatment-naïve regular sub-cohort with a mean ± SD VA improvement of 8.0 ± 17.7 letters, whereas treatment-naïve patients with irregular treatment experienced a considerably lower VA gain (2.8 ± 20.0 letters). Irregular treatment consistently correlated with inferior results in treatment-naïve patients. At month 12, the proportion of treatment-naïve patients who had experienced a worsening of ≥ 5 letters was 29.6% in the irregular sub-cohort versus 13.6% in the regular sub-cohort (P = 0.0049). However, among the treatment-naïve patients, the mean number of injections was significantly higher in the irregular than in the regular sub-cohort (8.0 ± 1.2 vs. 7.4 ± 0.6; P = 0.0001). Furthermore, compared with the treatment-naïve, regular sub-cohort, patients in the irregular sub-cohort had more visits (19.1 ± 8.6 vs. 16.1 ± 5.7), VA tests (14.2 ± 6.9 vs. 12.0 ± 4.6), and optical coherence tomography examinations (5.1 ± 3.7 vs. 3.4.0 ± 3.0). CONCLUSIONS: Although irregularly treated patients received more injections and more monitoring visits during the first year of IVT-AFL treatment, they experienced worse VA outcomes than regularly treated patients.

Reporting of Safety Events during Anti-VEGF Treatment: Pharmacovigilance in a Noninterventional Trial.

AIM: The prospective, noninterventional OCEAN study assessed the safety of intravitreal ranibizumab injections for treatment of neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion under real-world conditions in Germany. METHODS: Adults receiving ≥1 ranibizumab (0.5 mg) injections were recruited by 369 ophthalmologists and followed for 24 months. Information on adverse events (AEs) was reported by the treating physician or detected by the data management team. Collected information included observed AE, AE start and end date, intensity, causal relationship, outcome, severity, suspected drug, and actions taken. RESULTS: 2,687 AEs were reported for 1,176 of the 5,781 patients who had received a total of 32,621 injections: 27.4% nonserious AEs, 30.3% serious AEs, 27.3% nonserious adverse drug reactions (ADRs), and 15.0% serious ADRs. Most patients reported no AEs (79.7%) or only 1 AE (10.3%). AEs were most commonly reported in the Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) Eye disorders (9.4% of patients) and General disorders and administration site conditions (5.8%). The most frequent AEs by MedDRA preferred term (PT) were visual acuity reduced (3.5% of patients), intraocular pressure increased (2.5%), and drug ineffective (2.1%). AEs occurred most frequently after 3 or 4 injections (1,129 of 2,687 AEs). The proportion of AEs in the SOC Eye disorders decreased slightly with increasing number of injections, from 39.8% of events after 1 or 2 injections to 29.1% after 5 or more injections. Rates of the most frequently reported PTs did not show any consistent increase with increasing number of injections. A decrease in overall AE rates was observed over the study course. CONCLUSIONS: The results did not raise any new safety concerns for ranibizumab. The findings allow conclusions to be drawn on how pharmacovigilance data can be collected even more effectively in real-world studies to facilitate discussion on benefit-risk ratio.

Use of Imaging Modalities in Real Life: Impact on Visual Acuity Outcomes of Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration in Germany.

BACKGROUND: To date, there are limited prospective real-world data on the impact of optical coherence tomography (OCT) diagnostics on treatment outcomes in neovascular age-related macular degeneration (nAMD). Therefore, the prospective, noninterventional OCEAN study (NCT02194803) evaluated the use of OCT imaging and its impact on functional outcomes in Germany. METHODS: The use of OCT imaging for treatment decisions was documented in nAMD patients receiving intravitreal ranibizumab injections at 347 study centres. Best-corrected visual acuity (BCVA) testing and treatment were performed according to routine clinical practice and documented over 24 months. RESULTS: The majority of the 3,631 nAMD patients (59.6%) received a combination of OCT and fluorescein angiography imaging within the first 6 months. Over the remaining study course, this combination was used infrequently (range: 7.6% to 13.4%) and continually decreased over time; most patients received only OCT examinations (range: 48.9% to 52.5%; median: 3 within 12 months and 4 within 24 months). Subgroups according to the number of OCT examinations (≤4, rarely OCT examined; 5-8, moderately OCT examined; ≥8, well monitored) were associated with different treatment frequencies and outcomes: Rarely OCT-examined patients had received a median of 4 injections (range: 1-19) at 24 months; well-monitored patients had received a median of 8 injections (range: 1-21) at 24 months. Rarely OCT-examined patients had a mean change of BCVA of -0.3 letters (±26.1) at 24 months (n = 165); well-monitored patients showed a change of +2.0 letters (±20.8) at 24 months (n = 249). Time-to-response was greater for rarely examined than well-monitored patients, while duration-of-response was similar. CONCLUSION: Low number of visits as well as high number of treatment decisions without the use of OCT may contribute to undertreatment and poorer functional outcomes in patients undergoing ranibizumab treatment for nAMD in Germany. One potential reason for this could be that OCT was not covered by insurance for all patients during the study.

Application of subretinal fluid to close refractory full thickness macular holes: treatment strategies and primary outcome: APOSTEL study.

INTRODUCTION: Persisting macular holes (PMH) after surgical release of any epiretinal traction of the vitreous and adjacent membrane may rely on secondary firm adhesions between the retracted retina and adjacent retinal pigment epithelium. Secondary application of subretinal (SR)-fluid may release these adhesions followed by an anatomical closure. METHODS: Twelve surgeons applied in a consecutive case series SR-fluid in 41 eyes with PMH and reported retrospectively their initial surgical, anatomical and functional experience with this approach. RESULTS: The mean duration of the MH prior to SR-fluid application was 17 months (6-96 months). The mean age of the patients at the time of surgery was 72 years (54-88). The mean preoperative aperture diameter of the opening was 1212 µm (239-4344 µm), base diameter 649 µm (SD 320 µm). The mean preoperative BCVA prior to surgery was 0.1 (0.01-0.3). All patients (41/41) complained about reduced BCVA and a significant central scotoma (negative scotoma) in their central field of vision. The secondary closure rate for our PMH was 85.36% (35 out of 41 eyes) at 6 weeks after surgery. The postoperative BCVA improved to 0.22 (0.02-0.5). The application of SR-fluid was not associated with major intraoperative adverse effects. CONCLUSION: Remaining SR-adhesions may inhibit PMH closure. Their release by application of SR-fluid will lead to a fast and immediate anatomical closure in many cases without serious adverse events.

[Retinal laser treatment-avoiding mistakes]. / Retinale Lasertherapie ­ Fehler vermeiden.

Even in the era of intravitreal injection therapy (intravitreal operative injection of medication, IVOM) for the treatment of macular and retinal diseases, such as age-related macular degeneration (AMD), proliferative diabetic retinopathy (DR) and diabetic macular edema (DME) as well as proliferative stages and/or macular edema due to retinal vein occlusion (RVO), conventional retinal laser treatment is still of importance. It can be focally performed on an on-label basis for DME and macular edema due to branch RVO (BRVO) and its use as panretinal treatment for proliferative stages in retinal diseases as well as for the treatment of retinal holes is undisputed. The spectrum is extended by the treatment of less common diseases, such as retinal hemangioblastoma, macroaneurysms and subhyaloid macular hemorrhage. There is cause for concern that knowledge about the correct performance of retinal laser application might be shifted into the background due to an increase of IVOM treatment, which could lead to an increase in unnecessary errors. The aim of this manuscript is to increase awareness for the correct indications and execution of retinal laser treatment based on case examples of flawed or insufficient treatment.

[Lamellar macular holes : Morphological characteristics and treatment success]. / Lamelläre Makuladefekte : Morphologische Besonderheiten und therapeutischer Erfolg.

BACKGROUND: In recent years the high resolution of optical coherence tomography (SD-OCT) has led to a more exact and detailed imaging of different morphological types of lamellar macular holes (LMH). This resulted in new knowledge on the pathogenesis, morphology and progression of the disease; however, this also resulted in a lack of clarity in the terminology and in particular led to uncertainty in the treatment of these patients in clinical practice. OBJECTIVE: This article gives an overview on the morphological characteristics and treatment indications for LMH with the aim of enabling a clear differentiation compared to other morphological alterations in traction macular pathologies. MATERIAL AND METHODS: The evaluation is based on the current literature and own study data from the Department of Ophthalmology at the University of Munich, Germany. RESULTS: In eyes with LMH different morphological forms can be seen in SD-OCT. In addition to the known diagnostic criteria of irregular foveal contour, intraretinal splitting and defect of the inner foveal layers, the occurrence and characteristics of epiretinal tissue as well as the occurrence of photoreceptor layer defects can be evaluated. CONCLUSION: Further development of imaging techniques, such as SD-OCT led to improved visualization of different types of LMH. Decisions on treatment should be based on subjective complaints, best corrected visual acuity (BCVA), the clinical course, the presence of defects of the ellipsoid zone, occurrence and characteristics of epiretinal tissue. In cases of progression of symptoms and/or traction by the epiretinal tissue, an early surgical procedure has a good prognosis for functional and anatomical rehabilitation.

[Surgery of large and persistent macular holes]. / Chirurgie des großen und persistierenden Makulaforamens.

Modern macular hole surgery results in high closure rates of over 90% and good functional results especially in macular holes up to 400 µm in diameter. The standard of care in most of these cases consists of transconjunctival sutureless pars plana vitrectomy, peeling of the inner limiting membrane (ILM) around the hole, followed by gas tamponade and positioning of the patient. As closure rates and functional results decrease with larger macular hole diameters over approximately 400 µm, alternative surgical techniques have been introduced to improve anatomical and functional results in these cases. These techniques include the positioning of tissue within the macular hole to improve hole closure. This can be performed using an ILM flap or free flap technique and the transplantation of autologous retinal tissue, lens capsule or homologous amniotic tissue in or under the defect. An alternative promising approach is the attenuation of the rim of the hole by induction of a localized retinal detachment at the posterior pole which is achieved by subretinal injection of balanced salt solution (BSS) using a 41 gauge needle. The operation is completed by an endotamponade using gas or silicone oil.

Intravitreal Ranibizumab Therapy for Diabetic Macular Edema in Routine Practice: Two-Year Real-Life Data from a Non-interventional, Multicenter Study in Germany.

INTRODUCTION: The prospective, non-interventional OCEAN study examined the use of intravitreal ranibizumab injections for the treatment of diabetic macular oedema (DME) in a real-world setting in Germany. METHODS: Adults with DME receiving ≥ 1 ranibizumab (0.5 mg) injections were recruited by 250 ophthalmologists. Best-corrected visual acuity (VA) testing, imaging and treatments were performed according to the investigators' routine practice and documented over 24 months. RESULTS: The full analysis set included 1226 participants. Mean baseline VA was 60.6 [95% CI: 59.7; 61.5] Early Treatment Diabetic Retinopathy Study letters. VA improved by ≥ 15 letters in 21.5% and 23.5% of the participants at 12 months and 24 months, respectively. They received a mean number of 4.42 [95% CI: 4.30; 4.54] injections in the first year and 5.52 [95% CI: 5.32; 5.73] injections over 24 months, which was markedly lower than in clinical trials. Only 33.4% of the participants received an upload with four initial monthly injections as recommended by the German ophthalmologic societies. Time-to-event analyses that account for missing data inherent to a non-interventional study design demonstrated that participants receiving ≥ 7 injections in the first year had a faster response, but the duration of the response was shorter compared to the subgroups receiving 1-3 and 4-6 injections. Serious adverse events were reported for 143/1250 (11.4%) participants in the safety population. CONCLUSION: Under-treatment is a major problem of DME anti- vascular endothelial growth factor therapy under real life conditions. Despite fewer injections given compared to randomised controlled trials with a consequently reduced overall mean visual gain, a profound functional improvement (≥ 15 letters) was achieved over 2 years in 23.5% of eyes with DME. TRIAL REGISTRATION NUMBER: NCT02194803, ClinicalTrials.gov. FUNDING: Novartis Pharma GmbH, Nuremberg, Germany.

Calculating the individual probability of successful ocriplasmin treatment in eyes with VMT syndrome: a multivariable prediction model from the EXPORT study.

BACKGROUND/AIMS: To evaluate predictive factors for the treatment success of ocriplasmin and to use these factors to generate a multivariate model to calculate the individual probability of successful treatment. METHODS: Data were collected in a retrospective, multicentre cohort study. Patients with vitreomacular traction (VMT) syndrome without a full-thickness macular hole were included if they received an intravitreal injection (IVI) of ocriplasmin. Five factors (age, gender, lens status, presence of epiretinal membrane (ERM) formation and horizontal diameter of VMT) were assessed on their association with VMT resolution. A multivariable logistic regression model was employed to further analyse these factors and calculate the individual probability of successful treatment. RESULTS: 167 eyes of 167 patients were included. Univariate analysis revealed a significant correlation to VMT resolution for all analysed factors: age (years) (OR 0.9208; 95% CI 0.8845 to 0.9586; p<0.0001), gender (male) (OR 0.480; 95% CI 0.241 to 0.957; p=0.0371), lens status (phakic) (OR 2.042; 95% CI 1.054 to 3.958; p=0.0344), ERM formation (present) (OR 0.384; 95% CI 0.179 to 0.821; p=0.0136) and horizontal VMT diameter (µm) (OR 0.99812; 95% CI 0.99684 to 0.99941, p=0.0042). A significant multivariable logistic regression model was established with age and VMT diameter. CONCLUSION: Known predictive factors for VMT resolution after ocriplasmin IVI were confirmed in our study. We were able to combine them into a formula, ultimately allowing the calculation of an individual probability of treatment success with ocriplasmin in patients with VMT syndrome without FTHM.

Aflibercept for Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice in Germany: Twelve-Month Outcomes of PERSEUS.

PURPOSE: To explore real-world effectiveness of intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD) in Germany. DESIGN: A 24-month, prospective, noninterventional, noncontrolled, multicenter observational cohort study. PARTICIPANTS: Patients (n = 848) with nAMD treated with IAI. METHODS: Patients (n = 988) were screened at 67 study sites. Therapeutic decisions were made by the treating physician. Primary end point analysis was performed after 12 months for the entire study cohort and for predetermined subgroups of treatment-naïve and previously treated patients. Additionally, outcomes with regular injection intervals (bimonthly after 3 monthly injections) were compared with those of patients with irregularities in their treatment regimen. MAIN OUTCOME MEASURES: The primary end point was the mean change in visual acuity (VA) from baseline after 12 months. Other key end points included the proportions of patients gaining 15 letters or more and patients with reading vision (≥70 letters). Furthermore, the number of injections, anatomic measurements, and safety data were recorded. RESULTS: Mean ± standard deviation VA improvement was 5.3±17.4 letters in treatment-naïve patients and -0.1±15.6 letters in previously treated patients (P ≤ 0.0001), and that of the total study group was 2.9±16.8 letters. Baseline VA was 53.4±17.9 letters for treatment-naïve patients, 52.9±18.4 letters for previously treated patients, and 53.2±18.1 letters for the total patient population. Treatment pattern was associated with VA outcome: best outcomes-an average VA gain of 8.0±17.7 letters-were seen in treatment-naïve patients in the regularly treated population, whereas irregularly treated, treatment-naïve patients achieved a mean VA gain of only 4.0±17.1 letters. Among previously treated patients, regular treatment also was associated with better outcomes (+3.1±10.7 vs. -1.1±16.8 letters). For the total study group, the mean VA gain was the following: regularly treated population, 6.1±15.6 letters; irregularly treated population, 1.5±17.1 letters (P = 0.008). No cases of endophthalmitis were observed during the first 12 months of the study. Adverse events were in line with the known safety profile of IAI. CONCLUSIONS: After 12 months of treatment with IAI, treatment-naïve patients showed substantial functional benefit, whereas previously treated patients maintained their VA. With regular IAI treatment, it seems that similar results as those in pivotal IAI studies can be achieved in routine clinical practice.

The predictability of ocriplasmin treatment effects: is there consensus among retinal experts? Results from the EXPORT study.

PURPOSE: To evaluate the agreement and predictability of ocriplasmin treatment effects among retinal experts (raters) by assessment of retinal imaging data of eyes treated for vitreomacular traction in nine different centers in Germany and Austria. METHODS: Retrospective cohort study. Combined confocal near-infrared scanning laser ophthalmoscopy and spectral-domain optical coherence tomography images (Spectralis® device, Heidelberg Engineering GmbH, Germany) from 136 eyes of 135 subjects were reviewed by 14 raters using an internet-based grading database and a standardized questionnaire. In addition to the images taken within 2 days prior to treatment, age, gender, and lens status were disclosed to the raters. Treatment success was defined as a complete cleavage of the posterior vitreous cortex at day 28±5. Main outcome was the agreement and predictability among raters for assessment of treatment success. RESULTS: Raters generally accepted starting ocriplasmin treatment (chance for treatment success ≥ 1%) in 22.4 to 69.1% (median 53.2%) of eyes (moderate intra- and interrater agreements with kappa-values of 0.6 and 0.48). The likelihood for a high potential treatment success (equal or higher than 25%) was judged by the raters in 43.4% to 86.0% (median 62.6%) of eyes (moderate intra- and fair interrater agreements with kappa-values of 0.56 and 0.22). Allocating eyes for high potential treatment success overall increased the odds by 3.07, with odds ratios of single raters up to 4.06 to 6.16. CONCLUSIONS: These results underscore the importance of training health care providers in the evaluation of retinal imaging data and also to define characteristic morphological features better in the presence of vitreoretinal interface diseases. The better results of single raters in the predictability of treatment success by the allocation of eyes in the high-potential group indicates the high relevance of the meticulous analysis of retinal images.

VITRECTOMY FOR PERSISTENT MACULAR HOLES FOLLOWING OCRIPLASMIN INJECTION: A Comparative Multicenter Study.

PURPOSE: To determine functional and anatomical outcomes of pars plana vitrectomy for persistent full-thickness macular hole (MH) after intravitreal injection of ocriplasmin. METHODS: This is a multicenter retrospective interventional study of 37 eyes of 37 patients who underwent pars plana vitrectomy with internal limiting membrane peeling for persistent MH after ocriplasmin treatment between December 2013 and December 2015 and comparison with 35 eyes of 35 patients who were offered ocriplasmin injection but underwent pars plana vitrectomy alone without pharmacologic vitreolysis before surgery. In addition, 24 matched pairs (MH diameter at baseline ±5 µm) were analyzed. Clinical data such as visual acuity, intraoperative characteristics, and spectral domain optical coherence tomography images were reviewed. Main outcome measures were visual acuity and MH closure rate. RESULTS: After a mean follow-up period of 9 months, postoperative mean visual acuity showed no significant differences between ocriplasmin-treated eyes (logarithm of minimum angle of resolution 0.37 ± 0.26, Snellen 20/47) and eyes without ocriplasmin treatment (logarithm of minimum angle of resolution 0.39 ± 0.25; Snellen 20/49) (P > 0.9). After ocriplasmin injection, mean MH diameter enlarged from 217 ± 102 µm to 384 ± 239 µm (P < 0.001). Matched-pair analysis revealed no difference in gain of visual acuity between the first visit and the last follow-up (P = 0.29). Macular hole closure was observed in similar proportion in ocriplasmin-treated eyes (97%) and vitrectomy-only eyes (94%) (P > 0.5). CONLCUSION: Eyes with persistent MH after ocriplasmin injection showed significant visual improvement after pars plana vitrectomy. Matched-pair analysis revealed no statistical differences in functional and anatomical postoperative results comparing with eyes of similar MH diameter that proceeded directly to surgery without ocriplasmin pretreatment.