Louis Giavedoni

Effectiveness at 1 year of monthly versus variable-dosing intravitreal ranibizumab in the treatment of choroidal neovascularization secondary to age-related macular degeneration.

Purpose To evaluate the visual acuity results of monthly ranibizumab injections compared with a variable-dosing schedule for the treatment of neovascular age-related macular degeneration. Methods A retrospective study that compared two cohorts of consecutive patients. All patients were treatment naive, with baseline visual acuity of 20/400 or better, and completed 12 months of therapy. In the first group all patients received monthly injections. In the other group, after 3 monthly loading doses, a variable-dosing schedule was used, based on a monthly clinical assessment and optical coherence tomography. Results Fifty-six consecutive patients (60 eyes) were included. At 12 months the median number of injections were 12 and 8, respectively, and the mean change in Snellen visual acuity was an improvement of 0.27 logarithm of the minimum angle of resolution in the monthly treated group versus 0.21 logarithm of the minimum angle of resolution improvement in the variable-dosing group (P = 0.53). In the monthly treated group 96.8% of eyes lost <0.3 logarithm of the minimum angle of resolution versus 96.6% of eyes in the variable-dosing group (P = 1.0). Conclusion We were able to show that in our clinical setting patients achieved similar visual acuity results with either monthly injections or with a variable-dosing protocol. There was a trend toward better results with monthly treatment.

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 &mgr;m 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.

Bacterial endophthalmitis: 10-year review of the culture and sensitivity patterns of bacterial isolates

OBJECTIVE To examine the spectrum and sensitivity patterns of bacterial isolates derived from all culture-positive aqueous and vitreous samples submitted for culture and sensitivity analysis at our institution over a 10-year period. DESIGN Retrospective cohort study. PARTICIPANTS A total of 368 culture-positive aqueous and vitreous samples from 265 patients were reviewed. METHODS Over a decade extending from January 2000 through December 2009, all culture-positive aqueous and vitreous specimens at our institution were identified. Isolated bacterial pathogens and their in vitro antibiotic sensitivities were analyzed. RESULTS Approximately 86.4% of patients had positive cultures for either staphylococci (Staphylococcus aureus and coagulase-negative staphylococci [CNS]) or streptococci. Gram-negative bacteria were isolated in only 9.8% of patients. From 2000 to 2004, 81.2% and 55.9% of CNS isolates were sensitive to ciprofloxacin and cefazolin, respectively, compared with 41.2% and 23.5% of isolates in the last 5 years. Over the study period, ceftazidime retained 100% efficacy against the gram-negative isolates tested. Vancomycin was 99.6% effective against the gram-positive isolates tested. CONCLUSIONS The microbiology of pathogens in endophthalmitis is evolving, with an increase in streptococcal isolates and a decrease in CNS. The apparent lack of efficacy of conventionally used antibiotics and the emergence of increasingly resistant strains of bacteria may have significant implications in the management of bacterial endophthalmitis.

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 &mgr;m 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.

Differences in Surgical Performance of Internal Limiting Membrane Peeling for Macular Hole Repair Between Supervised Vitreoretinal Fellows and Vitreoretinal Faculty at a Single Institution

Purpose: To investigate the differences in surgical maneuvers between vitreoretinal fellows and experienced vitreoretinal surgeons (attendings) when performing internal limiting membrane (ILM) peel during macular hole (MH) surgery and repair. Methods: Prospective case series. Macular hole surgeries performed by fellows and attendings at St Michael’s Hospital (Toronto, Canada) were recorded during a 12-month period. Evaluation of recordings was masked. Total peel time (TPL) in seconds, total movement attempts initiating and extending ILM flaps, intrasurgical complications, and surgical efficiency (ratio of approaches leading to case progression to total approaches) were quantified. Results: A total of 145 surgeries were evaluated; 44 met inclusion and exclusion criteria. Of the 44 cases, 25 were performed by fellows and 19 by attendings. Mean TPL was shorter for attendings (336 vs 506 seconds, P = .0032). Attendings had a lower average total movement attempts (32.2 vs 43.2, P = .045) and average flap initiation attempts (16.1 vs 23.3, P = .042). Surgical efficiency was better for attendings (45% vs 37% of approaches led to case progression, P = .038). There was no significant difference between groups in total flap extension attempts or intrasurgical complications. Conclusions: Compared to fellows, attendings peel ILM in MH surgery faster, more efficiently with a lower number of flap initiation attempts and total movements.

Age-related macular degeneration: Is polypoidal choroidal vasculopathy recognized and treated?

OBJECTIVE To assess how polypoidal choroidal vasculopathy (PCV) is recognized and treated, and to assess whether treatment outcomes are different between Chinese and Caucasian Canadian patients with age-related macular degeneration (AMD). DESIGN Retrospective chart review. PARTICIPANTS 154 eyes from 135 Chinese patients and 2291 eyes from 1792 Caucasian patients who were newly diagnosed with either AMD or PCV and had more than 1 year of follow-up were included. METHODS All newly diagnosed AMD patients presenting to the Retina Service of 3 Toronto University Hospitals, between March 25, 2008, to September 30, 2014, were reviewed. RESULTS 10/154 eyes (6.5%) in Chinese Canadians and 16/2291 eyes (0.7%) in Caucasian Canadians were diagnosed as having PCV. Indocyanine green angiography (ICGA) was used to diagnose PCV in 20% of Chinese Canadians and 8.8% of Caucasian Canadians. Clinical practices with a larger percentage of Chinese patients were more likely to diagnose PCV in both Chinese (p = 0.004) and Caucasian patients (p = 0.03), were more likely to use photodynamic therapy (PDT) (p < 0.01), and had significantly greater central retinal thickness decrease (p < 0.001). CONCLUSION Our study has shown that PCV is under-recognized in a Canadian population, and ICGA is underutilized. In clinical practices with a greater portion of Chinese patients, PCV is more often recognized and PDT is used more liberally.