Posterior Approach Total Hip Arthroplasty Utilizing a Monoblock Dual-Mobility Construct Without Posterior Hip Precautions: A Series of 580 Hips With One Dislocation.

BACKGROUND: Instability remains a devastating complication following total hip arthroplasty. Here we describe a mini-posterior approach with a monoblock dual-mobility implant without "traditional posterior hip precautions" yielding excellent results. METHODS: There were 580 consecutive hips in 575 patients who underwent total hip arthroplasty utilizing a monoblock dual-mobility implant and a mini-posterior approach. With this technique, the acetabular component positioning does not rely on tradition intra-operative radiographic abduction and anteversion goals but rather uses patient-specific anatomic landmarks (anterior acetabular rim and, when visible, the transverse acetabular ligament) to set cup position; stability is assessed with a significant, dynamic intra-operative test of range of motion. Patients' mean age was 64 years (range, 21 to 94), and 53.7% were women. RESULTS: Mean abduction was 48.4° (range, 29° to 68°) and mean anteversion was 24.7° (range, -1° to 51°). Patient Reported Outcomes Measurement Information System scores improved in every measured domain from preoperative to final postoperative visit. There were seven (1.2%) patients who required reoperation, with mean time to reoperation of 1.3 months (range, one to 176 days). Only one patient (0.2%) who had a preoperative history of spinal cord injury and Charcot arthropathy dislocated. CONCLUSION: A posterior approach hip surgeon may want to consider using a monoblock dual-mobility construct and avoidance of traditional posterior hip precautions to achieve early hip stability with an extremely low dislocation rate and high patient satisfaction scores.

Fracture of Contemporary Femoral Stems: Common Trends in This Rare Occurrence.

BACKGROUND: Fracture of contemporary femoral stems is a rare occurrence in total hip arthroplasty. A knowledge gap remains regarding manufacturing, patient, and surgeon factors that may contribute to the increased risk of this complication. METHODS: We analyzed 13 contemporary fractured porous-coated femoral stems of various designs to determine cause and contributing factors of mechanical failure. Cases included 12 men and 1 woman who had an average age at index surgery of 53 years (range, 34 to 76 years). There were 10 of 13 patients who had a body mass index more than 30 (obese); 3 of the 10 had a body mass index more than 40. The mean time to fracture was 7.6 years (range, 7 months to 12 years). RESULTS: There were 4 titanium alloy stems that fractured an average of 3.6 years postrevision surgery for head/cup exchange and had associated iatrogenic mechanical and electrocautery damage to the femoral neck at fracture initiation sites. There were 6 modular stems that failed at the stem-sleeve or stem-neck interfaces with evidence of fretting corrosion. For 2 stem-neck fractures, mismatched head/stem combinations from different manufacturers resulted in untested mechanical offsets and loading. There were 2 proximal neck fractures and 1 mid-shaft fracture of coated cobalt-chromium alloy stems that occurred in 3 obese men. The neck fractures (10 to 12 years) were well-fixed stems. Lack of proximal fixation contributed to the mid-shaft fracture (7 months). CONCLUSION: While rare, femoral stem fractures pose catastrophic outcomes in primary and revision total hip arthroplasty. Manufacturing, patient, and surgical factors contributing to stem failures were identified, including patient obesity, heat-treatment reduction of mechanical properties, iatrogenic implant damage, and mixing of different vendor stems and heads.

Pearls and pitfalls in emergency CT neuroangiography through the lens of bias and error.

Computed tomography angiography (CTA) of the head and neck is central in emergency department (ED) evaluation of clinically suspected acute stroke and intracranial hemorrhage. Timely and accurate detection of acute findings is crucial for best clinical outcomes; missed or delayed diagnosis can be devastating. Our pictorial essay presents twelve CTA cases that provided significant diagnostic dilemmas to on-call trainees while reviewing current bias and error classifications in radiology. Among others, we discuss anchoring, automation, framing, satisfaction of search, scout neglect and zebra-retreat bias. Each imaging vignette depicts a potential diagnostic "pitfall" while introducing types of cognitive bias/error before concluding with a concrete "pearl" for CTA interpretation. We believe that familiarity with bias and error is particularly important in the ED setting where high case volume, high acuity and radiologist fatigue intersect. Particular attention to personal cognitive biases and these potential CTA pitfalls may help emergency radiologists transition from habit-driven pattern recognition to analytical thinking, ultimately improving diagnostic decision making.

Renoprotective Effects of Melatonin against Vancomycin-Related Acute Kidney Injury in Hospitalized Patients: a Retrospective Cohort Study.

Vancomycin is associated with nephrotoxicity, and the mechanism may in part be related to oxidative stress. In vitro and preclinical studies suggest that melatonin supplementation decreases oxidative stress. The objective of this study was to evaluate concomitant use of melatonin and vancomycin and the incidence of acute kidney injury (AKI). We performed a retrospective cohort study at a large community medical center. All consecutive patients admitted to the medical center between January 2016 and September 2020 who received vancomycin therapy alone or concomitantly with melatonin as part of ordinary care were considered for inclusion. The primary endpoint was the development of AKI, defined as an absolute increase in serum creatinine of ≥0.3 mg/dl or a ≥50% increase in serum creatinine. All data were analyzed using descriptive statistics. A multivariable logistic regression was constructed to account for potential confounding variables. We identified a total of 303 adult patients meeting inclusion and exclusion criteria treated with vancomycin, 101 of which received melatonin concomitantly. Overall baseline characteristics were similar between the two groups except for the incidence of bacteremia/sepsis. After controlling for the vancomycin area under the curve, baseline creatinine clearance, and intensive care unit admission in a multivariable logistic regression analysis, melatonin use was associated with a 63% decrease in AKI (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.14 to 0.96; P = 0.041). Melatonin use was associated with a significant reduction in vancomycin-related AKI. Although this was a retrospective study with a small sample size, given the magnitude of the difference seen, further large prospective studies are warranted.

Comparison between two multimodal imaging platforms: Nidek Mirante and Heidelberg Spectralis.

PURPOSE: To investigate the reliability and comparability of retinal measurements obtained with spectral-domain optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), confocal scanning laser ophthalmoscopy (cSLO) colour images, and fundus autofluorescence (FAF) between two multimodal imaging platforms in eyes with macular pathology and normal, healthy volunteers. METHODS: This cross-sectional, multi-centre, instrument validation study recruited 94 consecutive subjects. All participants underwent a dilated examination and were scanned consecutively on the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) and Nidek Mirante (Nidek Co. Ltd., Gamagori, Japan) devices. Agreement between device images were evaluated from measures of the central retinal thickness (CRT), presence of segmentation and fixation imaging artefacts (IA), foveal avascular zone (FAZ) measurements; as well as sensitivity and specificity values from the detection of atrophy on fundus autofluorescence (FAF), drusen, subretinal drusenoid deposits, geographic atrophy, epiretinal membrane, fibrosis and haemorrhage on multicolour imaging, and agreement between devices and groups. RESULTS: Compared with reference clinical examination, sensitivity values for the identification of retinal features using sole device images ranged from 100% for epiretinal membranes to 66.7% for subretinal drusenoid deposits (SSD). Mean absolute difference for CRT between OCT devices was 3.78 µm (95% confidence interval [CI]: - 21.39 to 28.95, P = 0.809). Differences in the superficial and deep capillary plexus FAZ area on OCTA between devices were not statistically significant (P = 0.881 and P = 0.595, respectively). IAs were significantly increased in the presence of macular pathology. CONCLUSION: Comparison of retinal measurements between the OCT devices did not differ significantly. Common ultrastructural biomarkers of multiple macular pathologies were identified with high sensitivities and specificities, with good agreement between graders, indicating that they can be identified with comparable confidence in retinal imaging between the two devices.

Macular Atrophy Incidence and Progression in Eyes with Neovascular Age-Related Macular Degeneration Treated with Vascular Endothelial Growth Factor Inhibitors Using a Treat-and-Extend or a Pro Re Nata Regimen: Four-Year Results of the MANEX Study.

PURPOSE: To compare the incidence and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a treat-and-extend (T&E) or a pro re nata (PRN) regimen over 4 years in a real-world setting. DESIGN: Four-year, multicenter, retrospective comparative study. PARTICIPANTS: Two hundred sixty-four patients with treatment-naive nAMD. METHODS: Consecutive patients with nAMD received anti-VEGF therapy according to a T&E (n = 163) or PRN (n = 101) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had undergone annual fundus autofluorescence (FAF) and OCT imaging using Heidelberg Spectralis. Two masked graders independently delineated areas of MA from serial FAF images using Heidelberg region finder software, and growth rates were calculated. Incident MA was assessed using proportional hazard ratios. MAIN OUTCOMES MEASURES: Macular atrophy incidence and progression over 4 years, association between treatment strategies, and number of injections. RESULTS: At baseline, MA was present in 24% and 20% of study eyes in T&E and PRN groups, respectively (P = 0.45). At year 4, 27% (34/124) and 25% (20/81) of eyes without baseline MA showed detectable MA in the T&E and PRN groups, respectively. In those with MA at baseline, the mean square root area of MA progressed by a rate of 0.4 ± 0.2 mm/year and 0.4 ± 0.1 mm/year in the T&E and PRN groups, respectively (P = 0.23). Multivariate analysis for baseline predictors of MA growth demonstrated that older age, poorer baseline visual acuity, and presence of retinal angiomatous proliferation had a higher risk of greater MA progression (P = 0.03). Regression analysis demonstrated no association between T&E and PRN treatment strategies with the risk of new MA developing during the 4 years of follow-up or the progression of pre-existing MA at year 4 (P = 0.692). CONCLUSIONS: Over 4 years, neither incidence nor progression of MA in eyes with nAMD treated with anti-VEGF injections was influenced by the treatment regimen and injection frequency. Eyes treated with a T&E regimen received more injections and achieved better visual outcomes compared with those treated with a PRN approach.

Prospective study of aflibercept for the treatment of persistent macular oedema secondary to retinal vein occlusions in eyes not responsive to long-term treatment with bevacizumab or ranibizumab.

IMPORTANCE: To examine the effect of switching from intravitreal bevacizumab or ranibizumab to aflibercept in eyes with persistent macular oedema due to retinal vein occlusion (RVO). BACKGROUND: We report the results of a prospective interventional study on the effect of aflibercept 2 mg in eyes with persistent macular oedema after long-term treatment with bevacizumab or ranibizumab. DESIGN: Non-randomized, prospective clinical trial. PARTICIPANTS: Eighteen eyes of eighteen patients were included. METHODS: Eyes with persistent macular oedema despite a minimum of four previous intravitreal bevacizumab/ranibizumab injections were recruited into this 48-week trial. Three loading doses of intravitreal aflibercept were administered every 4-weeks, thereafter every 8-weeks until week 48. MAIN OUTCOME MEASURES: Mean change from baseline in best corrected visual acuity (BCVA) as measured by early treatment diabetic retinopathy score (ETDRS) and central macular thickness (CMT) as measured by spectral domain optical coherence tomography (SD-OCT) at 48 weeks. RESULTS: Patients had received a mean of 40.0 ± 17.8 bevacizumab/ranibizumab intravitreal injections prior to switching to aflibercept. The mean number of previous injections administered in the 12-months preceding entry into the study was 10.2 ± 2.4. Mean vision change at week 48 was +21.1 ± 5.1 ETDRS letters in the BRVO group and +18.8 ± 5.9 letters at in the CRVO group (P < .001 for both groups). Mean decrease in CMT was 87.6 ± 48.8 µm and 191.0 ± 128.3 µm, in the BRVO and CRVO groups, respectively (P < .001). Using linear regression analyses, a higher number of previous intravitreal ranibizumab/bevacizumab injections and thicker pre-switch CMT were correlated with greater visual gains. CONCLUSION AND RELEVANCE: Switching to aflibercept from bevacizumab or ranibizumab in eyes with persistent macular oedema due to RVO can lead to functional and anatomical improvement. This effect was more obvious in eyes with a greater CMT prior to the switch.

Does functional assessment predict everyday visual functioning? Visual function testing and quality of life in mild/moderate age-related macular degeneration.

PURPOSE: To prospectively assess correlations between self-reported vision-related quality of life (VR-QoL) and clinical functional assessments in mild/moderate age-related macular degeneration (AMD). METHODS: Cross-sectional analysis of 64 participants with bilateral mild/moderate AMD. Microperimetry (MP), flicker perimetry (FP), multifocal electroretinogram (mfERG) findings, best-corrected visual acuity (BCVA) and the National Eye Institute Visual-Function Questionnaire-25 (NEI VFQ-25) were assessed for correlation between clinical testing results and NEI VFQ-25 findings. RESULTS: MP findings in the better eye were weakly correlated with NEI VFQ-25 subscales for colour, general, near and distance vision (p < 0.05 and R2 < 0.3 for all). FP findings and mfERG response density were not correlated with any subscale, apart from mfERG ring 1 response density and general health (p < 0.05, R2 = 0.41). mfERG latency was weakly correlated with general vision in the better eye in rings 2 and 4 (p < 0.05, R2 < 0.2). CONCLUSION: Functional assessment in mild/moderate AMD is at best, weakly correlated with patient-reported VR-QoL. Despite the growing awareness of the importance of VR-QoL outcomes in improving patient outcomes and satisfaction, surrogate markers of these outcomes remain elusive, and testing of VR-QoL in regular clinical settings remains difficult.

Saffron therapy for the treatment of mild/moderate age-related macular degeneration: a randomised clinical trial.

PURPOSE: To assess the efficacy and safety of oral saffron, a natural antioxidant, in treating mild/moderate age-related macular degeneration (AMD). METHODS: Randomised, double-blinded, placebo-controlled crossover trial of 100 adults (> 50 years) with mild/moderate AMD and vision > 20/70 Snellen equivalent in at least one eye. Exclusion criteria included confounding visual lesions, or significant gastrointestinal disease impairing absorption. Participants were given oral saffron supplementation (20 mg/day) for 3 months or placebo for 3 months, followed by crossover for 3 months. Participants already consuming Age-Related Eye Diseases Study (AREDS) supplements or equivalent maintained these. Primary outcomes included changes in best-corrected visual acuity (BCVA) and changes in multifocal electroretinogram (mfERG) response density and latency. Secondary outcomes included safety outcomes and changes in mfERG and BCVA amongst participants on AREDS supplements. RESULTS: Mean BCVA improved 0.69 letters (p = 0.001) and mean-pooled mfERG latency reduced 0.17 ms (p = 0.04) on saffron compared to placebo. Amongst participants on AREDS supplements, mean BCVA improved 0.73 letters p = 0.006) and mean-pooled mfERG response density improved 2.8% (p = 0.038). There was no significant difference in adverse event occurrence (p > 0.10). CONCLUSION: Saffron supplementation modestly improved visual function in participants with AMD, including those using AREDS supplements. Given the chronic nature of AMD, longer-term supplementation may produce greater benefits.

AFLIBERCEPT FOR PERSISTENT DIABETIC MACULAR EDEMA: Forty-Eight-Week Outcomes.

PURPOSE: To evaluate functional and anatomical outcomes after a switch from intravitreal bevacizumab to aflibercept in patients with persistent diabetic macular edema. METHODS: Prospective, single-arm, open-label clinical trial of patients with persistent diabetic macular edema, despite previous treatment with bevacizumab. Five loading doses of intravitreal aflibercept were administered every 4 weeks with subsequent injections administered every 8 weeks. Patients were reviewed every 4 weeks, and best-corrected visual acuity and central macular thickness were recorded. Primary outcome measures included change in central macular thickness and best-corrected visual acuity at week 48 compared with baseline. Paired t-tests were used to assess change between baseline and follow-up visits. RESULTS: At baseline, 43 eyes from 43 patients were recruited with a median (interquartile range) of 12 (7-24) previous intravitreal anti-vascular endothelial growth factor injections over a period of 18 (8-34) months. Mean ± SD central macular thickness reduced by 59 ± 114 µm (P = 0.002), and best-corrected visual acuity improved by 3.9 ± 7.0 letters (P = 0.001) after 48 weeks in the 41 patients who completed the trial. Best-corrected visual acuity improvements were more marked in patients who gained ≥5 letters after the first injection (8.9 ± 5.7 vs. 1.8 ± 6.5 letter gain at 48 weeks, P = 0.002), a difference which remained significant after regression analysis with baseline best-corrected visual acuity . Vision gains and central macular thickness reduction were similar in 9 fellow eyes eligible for inclusion being concurrently treated for diabetic macular edema with bevacizumab. CONCLUSION: Intravitreal aflibercept was effective in improving anatomical and visual outcomes among patients with an incomplete response to intravitreal bevacizumab with 48 weeks of follow-up. Patients with a good early response subsequent to switching had a better improvement in vision at 48 weeks.

Current Outcomes of Anti-VEGF Therapy in the Treatment of Macular Oedema Secondary to Branch Retinal Vein Occlusions: A Meta-Analysis.

PURPOSE: The current body of evidence on the efficacy and safety of anti-VEGFs for macular oedema secondary to branch retinal vein occlusion (BRVO) is steadily growing as large clinical trials and observational studies are continually completed. The aim of this meta-analysis is to analyse anatomical and functional outcomes in response to anti-VEGF therapy using evidence generated from a pooled analysis of current clinical trials and observational studies. METHODS: The current meta-analysis includes treatment of BRVO with aflibercept, bevacizumab and ranibizumab from randomised controlled trials and observational studies. Inclusion criteria included peer-reviewed publications with at least a 12-month follow-up period. On literature review using multiple electronic databases (PubMed, Embase and Cochrane), 22 studies met the inclusion criteria. Baseline patient characteristics, study design, sample size and 12- and 24-month change in best corrected visual acuity (BCVA) and central foveal thickness (CFT) as measured on optical coherence tomography imaging were pooled in a meta-analysis. Data were then stratified by study design and anti-VEGF therapy in subgroup analyses. RESULTS: A total of 1,236 eyes from 22 studies were included in this meta-analysis. Mean baseline BCVA ranged from 66 ETDRS letters (20/50 Snellen equivalent) to 35 letters (20/200 Snellen). Mean baseline CFT ranged from 406.0 to 681.0 µm. Anti-VEGF treatment demonstrated an overall mean improvement in BCVA at 12 months of 14 letters (95% CI 12.0 to 16.2, p < 0.001) and CFT reduction of 228 µm (95% CI -278.9 to -176.1, p < 0.001). The BCVA gains at 12 months were maintained to month 24 with a mean gain of 12.5 letters (95% CI 6.3 to 18.8, p < 0.001), as well as reduction of CFT of 238 µm (95% CI -336.0 to -140.2, p < 0.001). No cases of endophthalmitis or glaucoma were reported in any study. CONCLUSION: This meta-analysis confirms the comparable safety and efficacy of anti-VEGF therapies for patients with cystoid macular oedema secondary to BRVO. There is a need for randomised prospective comparative trials of anti-VEGF agents for BRVO.

Switching therapy from bevacizumab to aflibercept for the management of persistent diabetic macular edema.

PURPOSE: To evaluate the visual and anatomical outcomes following switching therapy from bevacizumab to aflibercept in patients with persistent diabetic macular edema (DME). METHODS: Patients with DME and central macular thickness (CMT) >300 µm on spectral domain optical coherence tomography (SD-OCT) despite at least 4 intravitreal bevacizumab injections in the prior 6 months were recruited for this prospective, single-armed, single centre, open-label clinical trial. Five loading doses of intravitreal aflibercept were administered every 4 weeks until week 16, at which point the treatment interval was extended to 8 weeks. All participants were reviewed every 4 weeks. At each visit, examination included best-corrected visual acuity (BCVA) measured with an Early Treatment of Diabetic Retinopathy Study chart and CMT measured with SD-OCT. Primary outcome measures were change in CMT and BCVA at week 24 compared with baseline. RESULTS: A total of 43 eyes from 43 patients were recruited for the study. At enrolment, study eyes had a mean ± standard deviation of 16.6 ± 11.5 previous intravitreal anti-VEGF injections over a period of 26.9 ± 23.8 months. Mean CMT reduced from 417 ± 91 µm at baseline to 380 ± 102 µm at 24 weeks (mean reduction 37 µm, p < 0.01). Mean BCVA improved from 67.8 ± 10.3 letters at baseline to 71.0 ± 10.1 letters at 24 weeks (mean 3.2 letter gain, p < 0.01). Eyes improving by ≥5 letters at 4 weeks following the first injection had improved vision outcomes at 24 weeks (6.8 ± 7.1 letters vs. 1.0 ± 4.7 letters, p < 0.01). CONCLUSION: Intravitreal aflibercept was effective in improving anatomical and visual outcomes among patients with incomplete response to intravitreal bevacizumab with 24 weeks of follow up. CLINICAL TRIAL REGISTRATION: ACTRN12614001307695.

Vision-related quality of life: 12-month aflibercept treatment in patients with treatment-resistant neovascular age-related macular degeneration.

PURPOSE: To assess changes in vision-related quality of life (VR-QoL) among patients with treatment-resistant neovascular age-related macular degeneration (nAMD) following intravitreal aflibercept treatment over 48 weeks. METHODS: We conducted a prospective study in which 49 patients with nAMD resistant to anti-vascular endothelial growth factor therapy were switched to intravitreal aflibercept. Patients were treated with three loading doses every 4 weeks followed by injections every 8 weeks, for a total of 48 weeks. Ophthalmic examinations performed at each visit included best-corrected visual acuity (BCVA) and central macular thickness (CMT) measurement. The National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) was used to assess VR-QoL at baseline and weeks 24 and 48. Changes in NEI VFQ-25 composite and subscale scores were analyzed using paired t tests. The relationship between the change in VR-QoL and changes in BCVA and CMT, and the impact of the better-seeing eye (BSE, defined as the eye reading the greater number of letters at baseline) vs. the worse-seeing eye (WSE, the fellow eye to the BSE) were assessed. RESULTS: Mean NEI VFQ-25 composite scores improved significantly at weeks 24 and 48 compared to baseline (4.5 ± 9.2 and 4.4 ± 11.8, respectively, all p < 0.01). Among subscales, general vision and near and distance activities showed significant improvements at weeks 24 and 48 (all p < 0.05). Improvement in the NEI VFQ-25 composite score was significantly associated with increased BCVA at week 48 (ß coefficient = 0.43, p = 0.029), but not with change in CMT (ß coefficient = -0.007, p = 0.631). There was no association between VR-QoL changes and BSE or WSE. CONCLUSION: Despite previous anti-VEGF treatment in this cohort, overall VR-QoL improved following aflibercept therapy over 48 weeks. This improvement was related to improved vision in treatment eyes regardless of whether they were the BSE or WSE.

Bilateral Neovascular Age-Related Macular Degeneration: Comparisons between First and Second Eyes.

PURPOSE: To compare 12-month outcomes and clinical presentations between first and second eyes of patients who developed neovascular age-related macular degeneration (nAMD) in both eyes and received ranibizumab intravitreal therapy (IVT). METHODS: This is a retrospective case series of 45 patients undergoing IVT for unilateral nAMD who subsequently developed second-eye nAMD. At each visit, both eyes underwent visual acuity (VA) measurement and optical coherence tomography (OCT). RESULTS: In second eyes, 53% were asymptomatic at baseline, with OCT retinal fluid as the only sign of nAMD among 33% of patients. In eyes with baseline VA >6/9, 82% of second treated eyes maintained this vision versus 12% of first eyes (p = 0.05). At 12 months, 70% of second eyes were fluid free versus 41% of first eyes (p = 0.02). CONCLUSIONS: A large proportion of patients are asymptomatic at diagnosis of second-eye nAMD. Early intervention following earlier detection of nAMD in the second eye may lead to improved clinical outcomes.

Choroidal Thickness and Microperimetry Sensitivity in Age-Related Macular Degeneration.

PURPOSE: To assess choroidal thickness (CT) and its relationship to retinal sensitivity in mild/moderate age-related macular degeneration (AMD). METHODS: Seventy-two eyes of 51 participants with mild/moderate AMD and 36 eyes of 18 age-matched normal participants were prospectively recruited to undergo enhanced-depth imaging optical coherence tomography (EDI-OCT) imaging and microperimetry (MP) functional assessment. OCT-measured CT and retinal thickness (RT) were matched with MP sensitivity at 13 retinal loci, and correlations were analysed. RESULTS: Patients with AMD had an average RT 56.5 µm greater than those without AMD (p < 0.001). There was no significant difference in CT between normal and AMD participants (p = 0.36). In patients without atrophy or pigment epithelial detachment, there was no correlation between MP sensitivity and CT (p = 0.08); however, a correlation between RT and MP was detected (b = 0.006, p = 0.046). Among patients without AMD, MP sensitivity was positively correlated with RT (b = 0.007, p < 0.001) and negatively correlated with CT (b = 0.0046, p = 0.035). CONCLUSIONS: CT does not correlate with retinal sensitivity in AMD. Although choroidal damage and impaired choroidal perfusion appear to be important concepts in AMD pathogenesis, increasing choroidal thinning may not be associated with worsening retinal function in AMD.

Diabetic macular oedema: pathophysiology, management challenges and treatment resistance.

Diabetic macular oedema (DMO) is the leading cause of vision loss in patients living with diabetes. DMO results from hyperglycaemia-induced activation of pathways that lead to oxidative stress and release of cytokines, impairing the inner and outer blood-retinal barriers. Improved understanding of the pathophysiological mechanisms leading to DMO have led to the development of effective therapies, including vitreoretinal surgery, laser photocoagulation, intravitreal anti-vascular endothelial growth factor drugs and corticosteroids. Advances in imaging, including fluorescein angiography and optical coherence tomography, have also enhanced diagnosis and management of the condition. Despite these advances, there remain patients who do not respond completely to therapy, reflecting the complex pathophysiology of DMO. These patients may be considered treatment-resistant. In this review, we summarise the pathophysiology of DMO, as well as the available treatments and their mechanism of action. Additionally, we focus on treatment-resistant disease and review the literature on potential options for managing this complication of diabetes.

Intravitreal Ranibizumab for neovascular Age-related macular degeneration in clinical practice: five-year treatment outcomes.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are the established standard of care for neovascular age-related macular degeneration (nAMD). However, data on long-term outcomes of this therapy are limited. The purpose of this study was to assess the visual and anatomical outcomes and safety profile of intravitreal ranibizumab in treating nAMD over a period of five years. METHODS: 208 patients (208 eyes) were included in this retrospective case series study. Intervention was an "as-needed" treatment model. Visual acuity (VA), central macular thickness (CMT), ophthalmic examination, and adverse events (AEs) were assessed in each visit. Snellen VA was converted to Early Treatment Diabetic Retinopathy Study letters for analysis. RESULTS: The average VA improved by 1.9 letters after one year (p = 0.017), and decreased by 2.4 letters over five years of treatment (p = 0.043). At the end of year five, 11.1 % of patients (23/208) had improved VA by more than 15 letters and 68.8 % (143/208) had VA improvement or loss less than or equal to 15 letters, while 20.2 % of patients (42/208) had a loss of more than 15 letters. Patients with VA of less than 35 letters at baseline showed significant VA improvement after five years of treatment. There was a positive relationship between injection numbers and VA improvement over the five-year period, after adjusting for age and baseline VA (p < 0.0005). Mean CMT decreased by 28.3 µm (p < 0.0005) over five years. Ocular AEs, serious adverse events (SAEs), and systemic SAEs occurred in 4.6 %, 0.48 %, and 2 % of patients, respectively, during the follow-up period. CONCLUSIONS: The use of intravitreal ranibizumab in an as-needed treatment regimen over a five-year period was effective in maintaining vision in patients with nAMD and in reducing macular thickness, with a relatively low rate of adverse and serious adverse events.

Response of pigment epithelial detachments to intravitreal aflibercept among patients with treatment-resistant neovascular age-related macular degeneration.

PURPOSE: To assess the effect of intravitreal aflibercept on pigment epithelial detachment (PED) in patients with treatment-resistant neovascular age-related macular degeneration. METHODS: Forty-six patients with vascularized PEDs participating in a wider, prospective clinical trial of treatment-resistant neovascular age-related macular degeneration received 2-mg aflibercept as 3 loading doses 1 month apart, followed by further 2-monthly doses over a total 12-month period. Change in PED dimensions and reflective properties were assessed by optical coherence tomography. Reflectivity was subclassified as solid (hyperreflective), hollow (hyporeflective), or mixed (elements of both). RESULTS: Aflibercept reduced PED height, width, and length at 48 weeks compared with baseline values (P ≤ 0.01 for all). Reductions in PED height were correlated with reductions in central macular thickness at 48 weeks (R = 0.36, P < 0.001). There was no significant correlation between PED height decrease and visual acuity changes at 48 weeks. Solid PEDs were less likely to experience reductions in all three dimensions than either hollow or mixed PEDs. CONCLUSION: Aflibercept is effective in reducing PED dimensions in treatment-resistant patients and is most effective in PEDs demonstrating some hyporeflective optical coherence tomography characteristics. Reduction in PED dimensions correlated with central macular thickness, but not with visual acuity changes. The role of PEDs as markers of disease requires further investigation; however, lesions should be monitored for retinal fluid recurrence.

Intravitreal Aflibercept for Treatment-Resistant Neovascular Age-Related Macular Degeneration: 12-Month Safety and Efficacy Outcomes.

PURPOSE: To prospectively assess the safety and efficacy of intravitreal aflibercept for treatment-resistant neovascular age-related macular degeneration (nAMD). METHODS: This prospective, non-randomized clinical trial included 49 patients with treatment-resistant nAMD who received 2 mg intravitreal aflibercept as 3 monthly loading doses, followed by injections every 2 months over 12 months. Inclusion criteria included active nAMD on fluorescein angiography at baseline and persistent intra- or subretinal fluid on optical coherence tomography (OCT) for ≥ 6 months prior to baseline with a minimum of 4 injections of bevacizumab and/or ranibizumab. Patients were assessed monthly for best-corrected visual acuity (BCVA), central retinal thickness (CRT) measured with OCT and occurrence of adverse events. Retinal pigment epithelium atrophy (RPEA) was assessed at baseline and at 12 months. RESULTS: Mean BCVA improved by 4.7 letters (95% CI: 2.1-7.3, p < 0.001) and CRT decreased by 97.2 µm (95% CI: 54.4-140.1, p < 0.001) at 12 months compared to baseline. Median RPEA area increased by 0.48 mm2 (range = -0.1 to 19.9, p < 0.001). There was 1 arterial thromboembolic event and 2 cases of submacular haemorrhage. CONCLUSION: In this cohort of treatment-resistant nAMD patients, intravitreal aflibercept was effective in improving vision and reducing exudation. Early visual and anatomic outcomes may predict longer-term response to treatment, but further assessment is required.

Colonoscopy after CT-diagnosed acute diverticulitis: Is it really necessary?

BACKGROUND: Computed tomography (CT) scans are commonly used to diagnose acute diverticulitis, but there are overlapping features between diverticulitis and colorectal cancer (CRC) on imaging studies. Hence, colonoscopy is typically recommended after an episode of acute diverticulitis to rule out underlying malignancy. Currently, 64-slice multidetector CT scanners are capable of providing higher-resolution images and may be able to distinguish malignancy from diverticular inflammation. We aimed to determine the prevalence of CRC among patients with CT-diagnosed acute diverticulitis. METHODS: We performed a retrospective study of patients with acute diverticulitis diagnosed on CT scan between December 2005 and December 2010 at St. Paul's Hospital, Vancouver, BC. Nonresidents were excluded. We reviewed CT scan reports that included the term "diverticulitis," reports of follow-up colonic evaluation within 1 year of diagnosis and pathology results. We queried the provincial cancer registry to ensure no cases of CRC were missed. RESULTS: A total of 293 patients had acute diverticulitis diagnosed on CT scan, but 8 were nonresidents and were excluded. Of the 285 included in the analysis, the mean age was 59.4 ± 15.1 years, and 167 (58.6%) were men. Among the 114 patients who underwent follow-up evaluation, malignancy was diagnosed in 4 (3.5%). The overall prevalence of malignancy among patients with CT-diagnosed diverticulitis was 1.4%. CONCLUSION: Routine endoscopic evaluation after an episode of diverticulitis diagnosed with high-resolution CT scan does not appear to be necessary. Selective approach in patients with protracted clinical course or those with mass lesion/obstruction on CT scan may be of benefit.

CONTEXTE: La tomodensitométrie (TDM) est couramment utilisée pour le diagnostic de la diverticulite aiguë, mais des caractéristiques sont communes à la diverticulite et au cancer colorectal (CCR) aux épreuves d'imagerie. On recommande donc en général la coloscopie après un épisode de diverticulite aiguë pour écarter un diagnostic de cancer sous-jacent. À l'heure actuelle, les appareils de TDM multidétecteurs à 64 barrettes peuvent fournir des images de haute résolution et permettent même de distinguer le cancer d'une inflammation diverticulaire. Nous avons voulu déterminer la prévalence du CCR chez les patients ayant présenté une diverticulite aiguë diagnostiquée par TDM. MÉTHODES: Nous avons procédé à une étude rétrospective sur des patients porteurs d'une diverticulite aiguë diagnostiquée à l'aide de TDM entre décembre 2005 et décembre 2010 à l'Hôpital St. Paul's de Vancouver, en Colombie-Britannique. Les non-résidents ont été exclus. Nous avons examiné les rapports de TDM incluant le terme « diverticulite ¼, les rapports d'examens du côlon au cours de l'année suivant le diagnostic et les rapports d'anatomopathologie. Nous avons interrogé le registre provincial sur le cancer pour nous assurer qu'aucun cas de CCR ne nous avait échappé. RÉSULTATS: En tout, 293 patients ont reçu un diagnostic de diverticulite à l'aide de la TDM; 8 étaient des non-résidents et ont été exclus. Parmi les 285 patients inclus dans l'analyse, l'âge moyen était de 59,4 ± 15,1 ans et 167 (58,6 %) étaient des hommes. Parmi les 114 patients qui ont subi un examen de suivi, le cancer a été diagnostiqué chez 4 (3,5 %). La prévalence globale du cancer chez les patients porteurs d'un diagnostic de diverticulite posé par TDM était de 1,4 %. CONCLUSION: L'évaluation endoscopique de routine après un épisode de diverticulite diagnostiquée à l'aide d'une TDM de haute résolution ne semble pas nécessaire. Une approche sélective chez les patients qui présentent une évolution clinique lente ou ceux qui présentent une lésion ou obstruction tumorale à la TDM pourrait être utile.