Secondary prophylaxis for Clostridioides difficile infection for patients on non-C. difficile antibiotics: a retrospective cohort study.

OBJECTIVES: Recurrent Clostridioides difficile infection (CDI) poses healthcare challenges and morbidity. Preventing recurrence with prophylactic oral CDI antibiotics lack consensus. METHODS: We used data from the largest healthcare provider in Israel to identify all adults aged 18 years or older diagnosed with a first episode of CDI (Index CDI) between February 2018 and December 2022 and subsequently received a non-CDI antibiotic within 2-8 weeks. Patients who received a concurrent prophylactic CDI antibiotic constituted the CDI prophylaxis group. Multivariable Cox proportional hazard regression models were used to examine the association of secondary CDI prophylaxis with CDI recurrence according to the severity of the index CDI (primary objective) and with 4- and 8-week all-cause mortality (secondary objective). RESULTS: A total of 434 eligible patients were included. Among them, 327 did not receive CDI antibiotic prophylaxis, while 107 did. CDI antibiotic prophylaxis was associated with a significant risk reduction of CDI recurrence with an adjusted HR of 0.51 (95% CI, 0.27-0.97). The magnitude of the association was modified by the severity of the index CDI episode (P for interaction 0.0182). Specifically, the HR for recurrence was 0.163 (95% CI 0.045-0.593) for non-severe CDI, and 1.242 (95% CI 0.524-2.946) for severe CDI. No significant association was found between CDI antibiotic prophylaxis and 4-8 weeks mortality. CONCLUSION: Secondary prophylaxis with CDI antibiotics appears to be associated with a reduced risk of recurrence in patients with previous non-severe CDI episode. Further studies are needed to confirm this finding.

Bronchiectasis with Chronic Rhinosinusitis Is Associated with Eosinophilic Airway Inflammation and Is Distinct from Asthma.

Rationale: Bronchiectasis is an airway inflammatory disease that is frequently associated with chronic rhinosinusitis (CRS). An eosinophilic endotype of bronchiectasis has recently been described, but detailed testing to differentiate eosinophilic bronchiectasis from asthma has not been performed. Objectives: This prospective observational study aimed to test the hypotheses that bronchiectasis with CRS is enriched for the eosinophilic phenotype in comparison with bronchiectasis alone and that the eosinophilic bronchiectasis phenotype exists as a separate entity from bronchiectasis associated with asthma. Methods: People with idiopathic or postinfectious bronchiectasis were assessed for concomitant CRS. We excluded people with asthma or primary ciliary dyskinesia and smokers. We assessed sputum and blood cell counts, nasal NO and fractional excreted NO, methacholine reactivity, skin allergy testing and total and specific immunoglobulin (Ig) E, cytokines in the sputum and serum, and the microbiome in the sputum and nasopharynx. Results: A total of 22 people with CRS (BE + CRS) and 17 without CRS (BE - CRS) were included. Sex, age, Reiff score, and bronchiectasis severity were similar. Median sputum eosinophil percentages were 0% (IQR, 0-1.5%) in BE - CRS and 3% (1-12%) in BE + CRS (P = 0.012). Blood eosinophil counts were predictive of sputum eosinophilia (counts ⩾3%; area under the receiver operating characteristic curve, 0.68; 95% confidence interval, 0.50-0.85). Inclusion of CRS improved the prediction of sputum eosinophilia by blood eosinophil counts (area under the receiver operating characteristic curve, 0.79; 95% confidence interval, 0.65-0.94). Methacholine tests were negative in 85.7% of patients in the BE - CRS group and 85.2% of patients in the BE + CRS group (P > 0.99). Specific IgE and skin testing were similar between the groups, but total IgE levels were increased in people with increased sputum eosinophils. Microbiome analysis demonstrated distinct microbiota in nasopharyngeal and airway samples in the BE + CRS and BE - CRS groups, without significant differences between groups. However, interactome analysis revealed altered interactomes in individuals with high sputum eosinophil counts and CRS. Conclusions: Bronchiectasis with CRS is associated with an eosinophilic airway inflammation that is distinct from asthma.

Association Between Guillain-Barré Syndrome and COVID-19 Infection and Vaccination: A Population-Based Nested Case-Control Study.

BACKGROUND AND OBJECTIVES: Existing data regarding occurrence of Guillain-Barré syndrome (GBS) after coronavirus disease 2019 (COVID-19) infection and vaccination are inconclusive. We aimed to assess the association between GBS and both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 vaccine. METHODS: We conducted a nested case-control study in a cohort of 3,193,951 patients aged 16 years or older, without a diagnosis of prior GBS, from the largest health care provider in Israel. Participants were followed from January 1, 2021, until June 30, 2022, for the occurrence of GBS. Ten randomly selected controls were matched to each case of GBS on age and sex. We assessed both SARS-CoV-2 infection and COVID-19 vaccine administration in the prior 6 weeks in cases and controls. RESULTS: Overall, 76 patients were diagnosed with GBS during follow-up and were matched to 760 controls. A positive test for SARS-CoV-2 was detected in 9 (11.8%) cases and 18 (2.4%) controls. An administration of COVID-19 vaccine was detected in 8 (10.5%) cases (all Pfizer-BioNTech [BNT162b2] vaccine) and 136 (17.9%) controls (134 Pfizer-BioNTech vaccine). Multivariable conditional logistic regression models showed that the odds ratio for GBS associated with SARS-CoV-2 infection and COVID-19 vaccine administration was 6.30 (95% CI 2.55-15.56) and 0.41 (95% CI 0.17-0.96), respectively. The results were similar when exposure to SARS-CoV-2 infection or COVID-19 vaccine administration was ascertained in the prior 4 and 8 weeks, although did not reach statistical significance for COVID-19 vaccine at 4 weeks. DISCUSSION: Our study suggests that SARS-CoV-2 infection is associated with increased risk of GBS, whereas Pfizer-BioNTech COVID-19 vaccine is associated with decreased risk of GBS.

Association between COVID-19 vaccination and myasthenia gravis: A population-based, nested case-control study.

BACKGROUND: Existing data regarding the link between COVID-19 vaccine and myasthenia gravis (MG) are scarce. We aimed to assess the association between Pfizer-BioNTech vaccine with both new-onset MG and MG exacerbation. METHODS: For the first aim, we conducted a nested case-control study in a cohort of 3,052,467 adults, without a diagnosis of MG, from the largest healthcare provider in Israel. Subjects were followed from January 1, 2021 until June 30, 2022 for the occurrence of MG. Ten randomly selected controls were matched to each case of new-onset MG on age and sex. For the second aim, a nested case-control study was conducted in a cohort of 1446 MG patients. Four randomly selected MG patients (controls) were matched to each case of MG exacerbation. Exposure to COVID-19 vaccine in the prior 4 weeks was assessed in cases and controls. RESULTS: Overall, 332 patients had new-onset MG and were matched with 3320 controls. Multivariable conditional logistic regression models showed that the odds ratio (OR) for new-onset MG, associated with COVID-19 vaccine, was 1.14 (95% CI 0.73-1.78). The results were consistent in sensitivity analysis that used more stringent criteria to define MG. Overall, 62 patients with MG exacerbation were matched to 248 MG controls. The multivariable OR for MG exacerbation, associated with COVID-19 vaccine, was 1.35 (95% CI 0.37-4.89). All results were similar when the prior exposure to COVID-19 vaccine was extended to 8 weeks. CONCLUSION: This study suggests that Pfizer-BioNTech vaccine is not associated with increased risk of new-onset nor exacerbation of MG.

TCF3 haploinsufficiency defined by immune, clinical, gene-dosage, and murine studies.

BACKGROUND: TCF3 is a transcription factor contributing to early lymphocyte differentiation. Germline monoallelic dominant negative and biallelic loss-of-function (LOF) null TCF3 mutations cause a fully penetrant severe immunodeficiency. We identified 8 individuals from 7 unrelated families with monoallelic LOF TCF3 variants presenting with immunodeficiency with incomplete clinical penetrance. OBJECTIVE: We sought to define TCF3 haploinsufficiency (HI) biology and its association with immunodeficiency. METHODS: Patient clinical data and blood samples were analyzed. Flow cytometry, Western blot analysis, plasmablast differentiation, immunoglobulin secretion, and transcriptional activity studies were conducted on individuals carrying TCF3 variants. Mice with a heterozygous Tcf3 deletion were analyzed for lymphocyte development and phenotyping. RESULTS: Individuals carrying monoallelic LOF TCF3 variants showed B-cell defects (eg, reduced total, class-switched memory, and/or plasmablasts) and reduced serum immunoglobulin levels; most but not all presented with recurrent but nonsevere infections. These TCF3 LOF variants were either not transcribed or translated, resulting in reduced wild-type TCF3 protein expression, strongly suggesting HI pathophysiology for the disease. Targeted RNA sequencing analysis of T-cell blasts from TCF3-null, dominant negative, or HI individuals clustered away from healthy donors, implying that 2 WT copies of TCF3 are needed to sustain a tightly regulated TCF3 gene-dosage effect. Murine TCF3 HI resulted in a reduction of circulating B cells but overall normal humoral immune responses. CONCLUSION: Monoallelic LOF TCF3 mutations cause a gene-dosage-dependent reduction in wild-type protein expression, B-cell defects, and a dysregulated transcriptome, resulting in immunodeficiency. Tcf3+/- mice partially recapitulate the human phenotype, underscoring the differences between TCF3 in humans and mice.

COVID Vaccine-Associated Uveitis.

PURPOSE: Following the pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, different vaccines were developed and approved by the main medical authorities under emergency protocol regulations. Although highly effective and well-tolerated in most patients, vaccines can uncommonly cause ocular adverse effects. In this article, the current evidence related to vaccine-associated uveitis is reviewed. METHODS: A literature review of uveitis post various SARS-CoV-2 vaccinations. RESULTS: Uveitis was reported following various forms of vaccinations but was more commonly seen following the Pfizer mRNA vaccine which is the most used vaccination worldwide. In western countries, the most common uveitis is mild anterior uveitis, developing within a week of first or subsequent vaccination with good resolution following appropriate topical steroid therapy in most cases. Posterior uveitis and particularly Vogt-Koyanagi-Harada disease was more prevalent in Asia. Uveitis may develop among known uveitis patients and those with other autoimmune diseases. CONCLUSION: Uveitis following Covid vaccinations is uncommon and has a good prognosis.

Improvised herding: Mapping biobehavioral mechanisms that underlie group efficacy during improvised social interaction.

Improvisation is a natural occurring phenomenon that is central to social interaction. Yet, improvisation is an understudied area in group processes and intergroup relations. Here we build on theory and research about human herding to study the contributions of improvisation on group efficacy and its biobehavioral underpinnings. We employed a novel multimodal approach and integrative method when observing face-to-face interactions-51 triads (total N = 153) drummed together in spontaneous-free improvisations as a group, while their electrodermal activity was monitored simultaneously with their second-by-second rhythmic coordination on a shared electronic drum machine. Our results show that three hypothesized factors of human herding-physiological synchrony, behavioral coordination, and emotional contagion-predict a sense of group efficacy in its group members. These findings are some of the first to show herding at three levels (physiological, behavioral, and mental) in a single study and lay a basis for understanding the role of improvisation in social interaction.

Use of a three-dimensional head-mounted digital visualization platform in cataract surgery.

OBJECTIVE: To report preliminary experience using the BeyeonicsOne (Beyeonics Vision, Haifa, Israel) digital visualization platform and the utilization of its three-dimensional (3D) head-mounted display (HMD) in cataract surgery. METHODS: An interventional case series including patients who underwent cataract surgery using the 3D HMD platform at the Tel Aviv Medical Center. The system uses the HMD unit to display high-resolution real-time 3D surgical field images. Collected data included patient demographics, ocular comorbidities, risk factors for complex cataract surgery, cataract grading, preoperative and postoperative best-corrected visual acuity (BCVA), and intra- and postoperative complications. RESULTS: In total, 60 eyes of 60 subjects (mean age 73.1 ± 8.4 years) were included. Mean preoperative BCVA was 0.40 ± 0.30 logMAR (Snellen equivalent ~20/50) and improved to 0.10 ± 0.10 logMAR (Snellen equivalent ~20/25, p < 0.001). None of the patients suffered BCVA loss. All procedures and follow-ups were uneventful except for one case of a posterior capsular tear and one case of post-surgical cystoid macular edema. CONCLUSION: The visualization platform and its embedded 3D head-mounted display can be easily used in routine cataract surgery with the added benefits of improved ergonomics, high picture quality and enhanced image control.

Herpetic Eye Disease Following the SARS-CoV-2 Vaccinations.

PURPOSE: To describe herpetic ocular infections following SARS-CoV-2 vaccinations. METHODS: A retrospective study of herpetic ocular infections after BNT162b2mRNA vaccination and a literature review. RESULTS: A cohort of five patients: three varicella zoster virus (VZV) and two herpes simplex virus (HSV) cases, as well as 19 literature cases: 9 cases of VZV and 10 cases of HSV post BNT162b2mRNA, AZD1222, mRNA-1273, and CoronaVac vaccinations. All cases presented within 28 days post vaccination. Most VZV and HSV cases (15/19) reported in the literature presented post first vaccine dose, while in our cohort 2 VZV cases presented post second dose and both HSV cases and one VZV case post third dose. The most common presentations were HZO with ocular involvement and HSV keratitis. All eyes had complete resolution; however, one had retinal detachment and three corneal scars. CONCLUSION: Herpetic ocular infections may develop shortly after SARS-CoV-2 vaccinations. Overall, the outcome is good.

Use of a Novel Three-dimensional Head-mounted Digital Visualization Platform in Corneal Endothelial Transplantation.

INTRODUCTION: To report the first endothelial keratoplasty procedures performed using a 3D digital head-mounted ophthalmic exoscope. METHODS: Three patients underwent Descemet stripping automated endothelial keratoplasty (DSAEK) using a 3D digital ophthalmic exoscope (Beyeonics One, Beyeonics Vision, Haifa, Israel) at the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. RESULTS: All procedures were uneventful, leading to resolution of corneal edema and vision improvement. Surgeons reported excellent visualization and minimal lag, almost negligible, with the benefits of improved ergonomics and the use of head gestures to control zoom, focus, brightness, and panning. There were no postoperative complications. CONCLUSION: The new 3D digital ophthalmic exoscope system can be successfully used in DSAEK surgery with potential advantages in ergonomics, picture quality, and image control. Further studies can compare this system with either standard operating microscopes or 3D heads-up display systems.

Ocular injury from foam dart (Nerf) blasters: a case series.

To report clinical outcomes following ocular injury from foam dart (nerf) blasters - a spring-loaded toy guns that fire foam-coated darts or bullets at a relatively low velocity. These guns gained popularity in recent years among children and adolescents. Eleven patients with ocular injuries from foam dart blasters were included in this retrospective, single-center study. Visual acuity (VA), intraocular pressure (IOP), and anterior segment, glaucoma-related, and vitreoretinal complications were recorded at each visit. The average age at presentation was 13.4 years and 82% were male. Mean initial VA was 6/12 (range 6/6 - 1/18); On initial examination, nine patients (82%) had hyphema, three (27%) had corneal abrasions, three (27%) had vitreous hemorrhage, and two (18%) had traumatic mydriasis. Four patients (36%) experienced glaucoma-related complications, including three (27%) with angle recession and three (27%) with increased IOP. Three patients (27%) were diagnosed with posterior segment injuries, including three (27%) with commotio retinae and one (9%) with severe retinal photoreceptor damage. No patients required surgical intervention. CONCLUSION: Foam dart blasters can cause severe blunt ocular trauma and permanent visual loss, illustrating the need for eye protection when handling these toys. WHAT IS KNOWN: • Foam dart blasters, a blanket term for spring-loaded toy guns that fire foam-coated darts or bullets at a relatively low velocity, have gained popularity in recent years among pediatric populations, with an increase in associated ocular injuries. • To date, scattered case reporting provides insufficient insight into the full clinical spectrum of injury and prognosis of foam dart blasters related ocular injury. WHAT IS NEW: • This case series characterizes the myriad foam dart blasters injuries that may afflict the eye, most of which are self-limiting, but some of which may result in poor visual outcomes and lifelong disability in pediatric patients. • We strongly recommend that all users wear eye protection while using foam dart blasters.

RadArnomaly: Protecting Radar Systems from Data Manipulation Attacks.

Radar systems are mainly used for tracking aircraft, missiles, satellites, and watercraft. In many cases, information regarding the objects detected by a radar system is sent to, and used by, a peripheral consuming system, such as a missile system or a graphical user interface used by an operator. Those systems process the data stream and make real-time operational decisions based on the data received. Given this, the reliability and availability of information provided by radar systems have grown in importance. Although the field of cyber security has been continuously evolving, no prior research has focused on anomaly detection in radar systems. In this paper, we present an unsupervised deep-learning-based method for detecting anomalies in radar system data streams; we take into consideration the fact that a data stream created by a radar system is heterogeneous, i.e., it contains both numerical and categorical features with non-linear and complex relationships. We propose a novel technique that learns the correlation between numerical features and an embedding representation of categorical features in an unsupervised manner. The proposed technique, which allows for the detection of the malicious manipulation of critical fields in a data stream, is complemented by a timing-interval anomaly-detection mechanism proposed for the detection of message-dropping attempts. Real radar system data were used to evaluate the proposed method. Our experiments demonstrated the method's high detection accuracy on a variety of data-stream manipulation attacks (an average detection rate of 88% with a false -alarm rate of 1.59%) and message-dropping attacks (an average detection rate of 92% with a false-alarm rate of 2.2%).

Epiretinal Membrane in Patients with Diabetic Macular Edema.

PURPOSE: The aim of the study was to compare anatomical and functional outcomes of pars plana vitrectomy (PPV) with epiretinal membrane (ERM) peeling in diabetes retinopathy patients with and without diabetic macular edema (DME). METHODS: A retrospective interventional case series of consecutive patients who underwent PPV with ERM peeling. Patients were divided into two groups: those with and without preoperative DME. Visual acuity (VA) and optical coherence tomography parameters were evaluated before surgery and during 12 months of follow-up. RESULTS: A total of 354 patients underwent PPV with ERM peeling, of which 51 met the inclusion criteria. Twenty-three were diagnosed with DME and were younger (66.3 ± 9.6 vs. 73.1 ± 8.2 years, p = 0.001), had longer diabetes mellitus (DM) duration (18.9 ± 7.1 vs. 14.3 ± 10.9 years, p = 0.04) and higher HbA1C% (7.6 ± 1.4 vs. 7.1 ± 1.3, p = 0.04). VA improved from 20/105 to 20/60 Snellen (p = 0.004) and central macular thickness decreased from 469.3 ± 64.9 µm to 331.1 ± 92.2 µm (p < 0.001) in the DME group and from 20/87 to 20/44 Snellen (p < 0.001) and from 463.1 ± 53.5 µm to 341.3 ± 49.5 µm (p = 0.01) in the non-DME group. Yearly intravitreal injection rate decreased from 5.9 ± 2.5 to 2.9 ± 3.0 (p < 0.001) injections in the DME group. CONCLUSIONS: DME patients with ERM experience significant improvement in VA, macular thickness, and yearly intravitreal injections after PPV with ERM peeling. DME patients are younger, with longer duration of DM and higher HbA1C% levels at presentation in comparison to diabetic ERM patients without DME.

Fertility and Sterility top videos of 2020.

OBJECTIVE: To objectively grade all video publications in Fertility and Sterility during 2020 and compile a list of the top 5 surgical videos. DESIGN: Descriptive presentation of the 5 highest scoring video publications from Fertility and Sterility in 2020 SETTING: Not applicable. PATIENT(S)/ANIMAL(S): Not applicable. INTERVENTION(S): J.F., Z.K., J.P.P., and S.R.L. acted as independent reviewers of all video publications. A standardized scoring method was used to score all videos. MAIN OUTCOME MEASURE(S): Up to 5 points were awarded for each of the following categories: scientific merit or clinical relevance of the topic, the clarity of the video, the use of innovative surgical technique, and video editing or the use of marking tools on the video to highlight the important features or surgical landmarks. This allowed a maximum score of 20 for each video. The numbers of YouTube views and likes were used as a tiebreaker if ≥2 videos scored similarly. The interclass coefficient from a 2-way random-effects model was calculated to assess for agreement between the 4 independent reviewers. RESULT(S): A total of 20 videos were published in Fertility and Sterility during 2020. After averaging scores from all 4 reviewers, a list of top 5 videos was created (Table 1). The overall interclass coefficient for the 4 reviews was 0.77 (95% confidence interval, 0.56-0.89). CONCLUSION(S): An overall substantial agreement was noted among the 4 reviewers. Five videos particularly stood out within the competitive peer reviewed publications. The subject matter of these videos ranged from complex surgical procedures, including transvaginal natural orifice surgery and advanced endometriosis to basic embryology laboratory topics that covered trophectoderm biopsy and novel intracytoplasmic sperm injection techniques.

Additive Value of a Face-to-Face Visit to Virtual Remote Decision in Patients with Neovascular Age-Related Macular Degeneration.

INTRODUCTION: The increasing high prevalence of neovascular age-related macular degeneration (nvAMD) in the aging population combined with the need for frequent monitoring and treatment for many years, especially in the COVID-19 era, raises the need to establish an effective, reliable, and safe follow-up and treatment model. This study evaluates the difference in treatment decisions comparing between the gold standard face-to-face clinical examination and virtual evaluation approach based only on visual acuity (VA) and optical coherence tomography (OCT) scans without clinical fundoscopic examination in nvAMD patients. METHODS: A single-center retrospective cohort study was conducted that compared an original "face-to-face" visit treatment decision regarding the need for anti-vascular endothelial growth factor drug, interval, and treatment regimen based on routine VA, spectral domain OCT imaging, and dilated fundus examination to two "virtual" treatment decisions based on evaluation of OCT scans and previous medical records before and after revealing VA data on the same nvAMD patients eyes. RESULTS: About 169 eyes of 114 patients were included in the study. Forty-nine patients (43%) suffered from bilateral nvAMD and had both eyes included in the study. Agreement between the "face-to-face visit treatment decision" and "virtual treatment decision" was noted in 74.6% and 71.6% eyes before and after revealing the patient's VA in the study visit, respectively. CONCLUSIONS: Virtual evaluation results in similar treatment decisions for nvAMD patients compared to standard face-to-face clinical examination.

Adherence with direct oral anticoagulants in patients with atrial fibrillation: Trends, risk factors, and outcomes.

BACKGROUND: Adherence to direct oral anticoagulants (DOACs) remains a concern among non-valvular atrial fibrillation (AF) patients. We aimed to assess patterns of adherence with DOACs and examine their association with ischemic stroke and systemic embolism (SE). METHODS: This retrospective cohort study includes all adult members of Clalit Health Services, the largest healthcare provider in Israel, with newly diagnosed non-valvular AF between January 2014 and March 2019, who initiated DOACs within 90 days of AF diagnosis and used DOACs exclusively. Adherence was assessed using the proportion of days covered (PDC) over the first year of treatment, and high adherence was defined as PDC ≥80%. Regression models were used to identify predictors of high adherence to DOACs and to examine the association between adherence and stroke or SE. RESULTS: Overall 15,255 patients were included in this study. The proportion of highly adherent (PDC ≥80%) DOACs users was around 75% and decreased slightly over the years. On multivariable analyses, the likelihood of high adherence to DOACs increased with age and across higher socioeconomic classes, and was more likely among females, Jews, statins users, and patients with CHA2DS2-VASc score ≥2. Risk of stroke and SE was lower among highly adherent DOACs users; adjusted HR 0.56 (95% CI, 0.45-0.71), compared to users with PDC <80%. CONCLUSIONS: Adherence with DOACs is still sub-optimal among non-valvular AF patients, resulting in a higher risk of stroke and SE.

PIGMENT EPITHELIAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION: Long-Term Visual Acuity May Improve With Higher Injection Index.

PURPOSE: To define injection index (II) and assess its impact on visual acuity (VA) in pigment epithelial detachment from age-related macular degeneration over 5 years. METHODS: Injection index is defined as the mean anti-vascular endothelial growth factor injections per year from presentation. A retrospective study of 256 eyes in 213 patients was performed. Patients were stratified by II (high: ≥9, low: <9). RESULTS: Baseline characteristics showed no differences across II groups. Mean (range) follow-up, in years, was 5.02 (1.04-12.74) for all patients. Mean logMAR VA (Snellen VA) were 0.60 (20/80) and 0.56 (20/73) at baseline, 0.52 (20/66) and 0.59 (20/78) at Year 1, 0.45 (20/56) and 0.67 (20/94) at Year 2, 0.38 (20/48) and 0.66 (20/91) at Year 3, 0.41 (20/51) and 0.89 (20/155) at Year 4, and 0.35 (20/45) and 0.79 (20/123) at Year 5 for the high and low II groups, respectively. Linear regression analysis showed a gain of 0.5 approxETDRS letters with each additional injection per year. CONCLUSION: Increased II was associated with better mean VA, suggesting that long-term continuous vascular endothelial growth factor suppression may improve VA in eyes thought to carry poor prognoses.