Research productivity of ophthalmology residents and its relationship to academic career outcomes.

OBJECTIVE: To assess the impact of ophthalmology resident research and its relationship to subsequent practice. DESIGN: Cross-sectional study. PARTICIPANTS: Three hundred and twenty residents of Canadian ophthalmology programs graduating between 2009 and 2020. METHODS: Bibliometric data were obtained for each resident from Scopus. Indices of scholarly productivity included number of publications, h-index, m-quotient, and total citations. Demographic and career data were obtained from faculty listings and professional and regulatory web sites. Career outcomes included location and subspecialty of fellowship training and type of ultimate practice (academic vs community). RESULTS: In total, 208 of 320 graduates (65%) published at least 1 peer-reviewed article during residency. Bibliometric indices, including numbers of papers, h-index, and total citations, were significantly higher for male residents and residents who pursued academic and subspecialized practices. No significant trends were seen regarding scholarly productivity and fellowship match outcomes (e.g., location and subspecialty of fellowship). The bulk of resident research projects was of lower tiers of evidence, including retrospective studies (n = 111) and case reports (n = 108). Five-year scholarly impact of resident research decreased over time (h-index, m = -0.14; p < 0.01) despite stable publication volumes. CONCLUSIONS: Greater scholarly activity in residency corresponds to more academic and subspecialized practices but is not associated with type of fellowship. The impact of resident research declined between 2009 and 2020. Sex-based disparities exist.

Changes in Aqueous Cytokine Levels Following Intravitreal Aflibercept in Treatment-Naive Patients with Diabetic Macular Edema.

Purpose: To investigate the changes in aqueous humor cytokine levels in response to short-term aflibercept therapy in treatment-naive patients with center-involving diabetic macular edema (DME). Methods: This is a prospective cohort study that included patients with treatment-naive DME with central subfield macular thickness ≥310 µm on optical coherence tomography from July 2015 to May 2017. Patients received 3 monthly intravitreal aflibercept injections. Aqueous samples for cytokine analysis were obtained before the first and third injections. Levels of various cytokines were measured using multiplex immunoassay. Main outcome measures were changes in aqueous cytokine levels from baseline to month 2. Results: A total of 17 patients were enrolled and 16 completed the study. The mean age was 57.2 ± 8.1 years. The following cytokines were significantly higher at month 2 versus baseline: transforming growth factor-beta (TGF-ß)1 (P = 0.004), TGF-ß2 (P = 0.017), inducible protein (IP)-10 (P = 0.011), and hepatocyte growth factor (HGF) (P = 0.02). There were significant reductions in the levels of vascular endothelial growth factor (VEGF) (P < 0.001), placental growth factor (PlGF) (P = 0.028), interleukin (IL)-6 (P = 0.011), and platelet-derived growth factor-AA (PDGF-AA) (P = 0.003). Conclusions: In treatment-naive patients with DME, short-term aflibercept therapy not only results in VEGF and PlGF suppression, but also leads to reduced levels of IL-6 and PDGF-AA and higher concentrations of TGF-ß1, TGF-ß2, HGF, and IP-10.

Vision-Related Functioning in Patients Undergoing Pneumatic Retinopexy vs Vitrectomy for Primary Rhegmatogenous Retinal Detachment: A Post Hoc Exploratory Analysis of the PIVOT Randomized Clinical Trial.

Importance: Although rhegmatogenous retinal detachment (RRD) repair techniques have high anatomical reattachment rates, there may be differences in various aspects of postoperative vision-related quality of life (VRQoL). Objective: To explore the differences in various aspects of VRQoL between pneumatic retinopexy (PnR) and pars plana vitrectomy (PPV) following RRD repair. Design, Setting, and Participants: Post hoc exploratory analysis of the the Pneumatic Retinopexy vs Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes randomized clinical trial conducted between August 2012 and May 2017 at St Michael's Hospital, Toronto, Ontario, Canada. Patients with RRD with a single break or multiple breaks within 1 clock hour of detached retina in the superior 8 clock hours of the retina with any number, location, and size of retinal breaks or lattice degeneration in attached retina. Main Outcomes and Measures: Differences in the 25-Item National Eye Institute Visual Function Questionnaire 12 subscale scores between the PnR and PPV groups at 6 months following RRD repair. Results: A total of 160 patients were included in this analysis, with 81 patients (92%) and 79 patients (90%) in the PnR and PPV groups, respectively. The PnR group consisted of 32% women with a mean (SD) age of 60.9 (9.3) years, while the PPV group consisted of 38% women with a mean (SD) age of 60.3 (7.6) years. For the 152 patients with 6-month follow-up (75 patients in PnR [85%] and 77 patients in PPV [88%]), there was evidence for an association of PnR with superior vision-related functioning compared with PPV for several subscales. There were no differences between groups at 1 year. After adjusting for age, sex, baseline macular status, visual acuity in the nonstudy eye, and lens status, patients who underwent PnR had higher scores for distance activities (mean [SD] PnR, 88.7 [13.4]; PPV, 82.8 [17.1]; adjusted difference, 6.5; 95% CI, 1.6-11.4; P = .01), mental health (mean [SD] PnR, 84.3 [17.4]; PPV, 78.7 [21.1]; adjusted difference, 6.7; 95% CI, 0.4-13; P = .04), dependency (mean [SD] PnR, 96.1 [10.1]; PPV, 91.1 [18.6]; adjusted difference, 5.7; 95% CI, 0.6-10.8; P = .03), and peripheral vision (mean [SD] PnR, 91.6 [16.2]; PPV, 81.2 [24.4]; adjusted difference, 10.8; 95% CI, 4.3-17.4; P = .001) at 6 months. Conclusions and Relevance: These findings demonstrate that patients undergoing PnR for RRD report higher mental health scores and superior vision-related functioning scores in several subscales of the 25-Item National Eye Institute Visual Function Questionnaire during the first 6 months postoperatively compared with PPV. Trial Registration: ClinicalTrials.gov Identifier: NCT01639209.

Aqueous Humor Cytokines and Long-Term Response to Anti-Vascular Endothelial Growth Factor Therapy in Diabetic Macular Edema.

PURPOSE: To determine the association of aqueous humor cytokine concentrations with long-term treatment response to anti-vascular endothelial growth factor (VEGF) agents in diabetic macular edema (DME). DESIGN: Retrospective case series. METHODS: Pooled data of aqueous humor cytokine concentrations collected at baseline and 2-month follow-up (2 injections) for treatment-naïve eyes with center-involving DME previously enrolled in a prospective study were reviewed. Subjects receiving intravitreal anti-VEGF injections outside of study protocol as per standard of care were classified into Responders versus Nonresponders based on qualitative assessment of optical coherence tomography for persistence of DME at longitudinal follow-up visits. RESULTS: Of the 41 eyes, 85% were classified as Responders with a significant decline in baseline central subfield thickness and macular volume (P values < .001), and 15% were identified as Nonresponders to anti-VEGF therapy over 51.4 ± 18.7 months of follow-up. No significant difference in baseline aqueous humor VEGF concentration was noted, while at the 2-month follow-up the Nonresponder group had a significantly higher VEGF concentration compared with the Responder group (451.5 ± 690.9 pg/mL vs 113.7 ± 211.4 pg/mL; P = .02). The Responder group also demonstrated a significant decline from baseline to 2-month follow-up in concentration of intercellular adhesion molecule-1 (P < .001), interleukin-10 (P = .041), monocyte chemotactic protein-1 (P = .046), placental growth factor (P = .027), and transforming growth factor-ß2 (P = .017). CONCLUSIONS: Aqueous humor cytokine concentrations serve as an early biomarker for long-term response to anti-VEGF therapy and may enable more effective treatment regimens that improve anatomical outcomes in eyes with DME.

Aqueous Humor Cytokine Levels and Anatomic Response to Intravitreal Ranibizumab in Diabetic Macular Edema.

Importance: Variability in response to anti-vascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME) remains a significant clinical challenge. Biomarkers could help anticipate responses to anti-VEGF therapy. Objectives: To investigate aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and to determine the association between baseline aqueous levels and anatomic response. Design, Setting, and Participants: In this prospective multicenter cohort study, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 µm or greater on spectral-domain optical coherence tomography (SD-OCT), were recruited from December 22, 2011, to June 13, 2013 and statistical analysis were performed from March 1, 2017, to June 1, 2017. A total of 48 participants proceeded to follow-up. Interventions: Participants received monthly injections of ranibizumab, 0.5 mg, for 3 months. Aqueous fluid for cytokine analysis was obtained at baseline and repeated at the 2-month visit. Multiplex immunoassay was carried out in duplicate for VEGF, placental growth factor, transforming growth factor beta 2, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), IL-8, IL-10, vascular intercellular adhesion molecule, and monocyte chemoattractant protein 1. Main Outcomes and Measures: Baseline and 2-month change in aqueous cytokine levels, 3-month change in SD-OCT central subfield thickness and macular volume (MV), and the statistical association between baseline aqueous cytokine levels and these measures of anatomic response to ranibizumab in center-involving DME. Results: Among the 48 participants, the mean (SD) age was 61.9 (7.1) years and 36 participants (75.0%) were men. The following cytokines were lower at month 2 vs baseline: ICAM-1 (median change, -190.88; interquartile range [IQR], -634.20 to -26.54; P < .001), VEGF (median change, -639.45; IQR, -1040.61 to -502.61; P < .001), placental growth factor (median change, -1.31; IQR, -5.99 to -0.01; P < .001), IL-6 (median change, -38.61; IQR, -166.72 to -2.80; P < .001), and monocyte chemoattractant protein 1 (median change, -90.13; IQR, -382.74 to 109.47; P = .01). When controlling for age, foveal avascular zone size, and severity of retinopathy, multiple linear regression determined that increasing baseline aqueous ICAM-1 was associated with a favorable anatomic response, in terms of reduced SD-OCT MV at 3 months (every additional 100 pg/mL of baseline ICAM-1 was associated with a reduction of 0.0379 mm3; P = .01). Conversely, increasing baseline aqueous VEGF was associated with a less favorable SD-OCT MV response at 3 months (every additional 100 pg/mL of baseline VEGF was associated with an increase of 0.0731 mm3; P = .02) and was associated with lower odds of being a central subfield thickness responder (odds ratio, 0.868; 95% CI, 0.755-0.998). Conclusions and Relevance: Elevated aqueous ICAM-1 and reduced VEGF levels at baseline are associated with a favorable anatomic response to ranibizumab in DME, although there is not always direct correlation between anatomic and visual acuity response.

Pain Associated With a Subconjunctival Cefazolin-Lidocaine Mixture in Retinal Surgery:A Randomized Control Trial.

BACKGROUND AND OBJECTIVE: The purpose of this randomized, single-masked clinical trial is to explore whether cefazolin mixed with 2% lidocaine can reduce pain. PATIENTS AND METHODS: Patients naïve to ophthalmic surgery were randomized to subconjunctival injection of either a 0.5 mL cefazolin-balanced salt solution (0.3 mL cefazolin and 0.2 mL balanced salt solution) or 0.5 mL cefazolin-lidocaine solution (0.3 mL cefazolin and 0.2 mL 2% lidocaine) during retinal surgery with a retrobulbar block. Pain scores were obtained at the start of surgery, middle of surgery, before and after cefazolin administration, and postoperatively. RESULTS: A total of 54 patients were recruited; 44.6% were male, and the mean age was 60.1 years ± 13.5 years. There were no statistically significant differences between the groups' operative characteristics or pain scores at each study time point. CONCLUSION: In pars plana vitrectomy with or without phacoemulsification and intraocular lens insertion, subconjunctival cefazolin mixed with lidocaine conferred no added analgesic benefit. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:881-886.].

AQUEOUS HUMOR CYTOKINE LEVELS AS BIOMARKERS OF DISEASE SEVERITY IN DIABETIC MACULAR EDEMA.

PURPOSE: To determine whether aqueous cytokine levels correlate with disease severity in diabetic macular edema. METHODS: A prospective cross-sectional study of 49 adults with diabetes mellitus, centre-involving diabetic macular edema and central subfield macular thickness ≥310 µm on spectral domain optical coherence tomography. Clinical examination and aqueous sampling were carried out before an initial injection of ranibizumab. Multiplex immunoassay of sample was carried out for vascular endothelial growth factor, placental growth factor, transforming growth factor beta, intercellular adhesion molecule-1, interleukin (IL)-2, IL-3, IL-6, IL-8, IL-10, IL-17, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and epidermal growth factor. Multivariate robust regression models were constructed, and adjusted for age, lens status, or severity of retinopathy, and size of foveal avascular zone. RESULTS: Spectral domain optical coherence tomography macular volume was an excellent measure of disease severity, correlating strongly with central subfield macular thickness (P < 0.001), best-corrected Snellen visual acuity (P < 0.001), and baseline diabetic retinopathy severity (P = 0.01). Elevated aqueous intercellular adhesion molecule-1 correlated with greater macular volume (P = 0.002). No aqueous cytokine, including VEGF, correlated with central subfield macular thickness. There was an association between IL-10 levels and best-corrected Snellen visual acuity (P = 0.03). CONCLUSION: Aqueous intercellular adhesion molecule-1 correlates with disease severity as measured by macular volume on spectral domain optical coherence tomography, and IL-10 is associated with BCVA. Intercellular adhesion molecule-1 may be a clinically useful biomarker for diabetic macular edema severity.

PROPORTION OF PATIENTS WITH MACULAR HOLE SURGERY WHO WOULD HAVE BEEN FAVORABLE OCRIPLASMIN CANDIDATES: A Retrospective Analysis.

PURPOSE: To identify favorable ocriplasmin candidates from a cohort of idiopathic full thickness macular hole surgery patients. METHODS: The records of patients with full thickness macular hole who underwent pars plana vitrectomy surgery between 2011 and 2015 were reviewed. Clinical data collected included patient demographics, pre- and post-operative Snellen visual acuity, optical coherence tomography findings, and lens status. The authors defined "favorable" ocriplasmin candidates as patients with focal vitreomacular traction, no epiretinal membrane, and hole size ≤400 µm. The authors further categorized "optimal" candidates as age ≤65, phakic, no epiretinal membrane, with focal vitreomacular traction, and hole size ≤400 µm. RESULTS: The records of 238 patients were assessed; 30.7% were male while mean age was 68.6 ± 8.3 years. The mean logMAR acuity was 1.2 (Snellen 20/317) preoperatively and 0.90 (Snellen 20/159) postoperatively. Optical coherence tomography findings indicated that 46.5% of the macular holes studied were less than ≤400 µm in size, 14.8% had an epiretinal membrane, and 25.3% had vitreomacular traction. A total of 17.7% of study patients were found to be favorable candidates, whereas 3.8% were optimal ocriplasmin candidates. CONCLUSION: Only a minority of full thickness macular hole surgical candidates in this cohort would be considered favorable ocriplasmin candidates.