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.

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.

Post-surgical versus post-intravitreal injection endophthalmitis: changing patterns in causative flora.

IMPORTANCE: Endophthalmitis is a serious complication of intraocular procedures: knowledge of its causative organisms and outcomes may guide prevention and treatment. BACKGROUND: To determine the outcomes and spectrum of causative organisms in acute post-procedural endophthalmitis. DESIGN: A retrospective observational case series performed at a tertiary referral hospital during the period 1 July 2012 to 31 July 2017. PARTICIPANTS: Two hundred and forty-eight patients diagnosed with acute (≤ 6 weeks post-inciting event) endophthalmitis. METHODS: Chart review of microbiological and clinical data. MAIN OUTCOME MEASURES: The main outcome measure was odds of any improvement in visual acuity (3 months versus presentation). Secondary outcomes included causative organism, likelihood of vitrectomy and likelihood of evisceration. RESULTS: One hundred and ninty cases were post-cataract surgery or post-intravitreal injection (49 and 141, respectively). Causative organisms were identified in 45% of post-cataract surgery and 54% of post-injection cases (OR = 0.69; P = 0.61). Staphylococcus epidermidis was the most frequent causative organism. Streptococcus species accounted for 32% of post-surgical and 7% of culture-positive post-injection cases (OR = 6.63; P = 0.02). At 3 months, 81% of post-surgical and 84% of post-injection cases had improved BCVA over presentation (OR 0.59; P = 0.61). CONCLUSIONS AND RELEVANCE: S. epidermidis is the most common causative organism. In contrast to other studies, we did not find evidence for an increased odds of Streptococcus spp. endophthalmitis following intravitreal injection. This may in turn reflect guideline-driven changes in practice.

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.

Resident training in a new robotic thoracic surgery program.

BACKGROUND: The volume of robot-assisted operations has drastically increased over the past decade. New programs have focused on training surgeons, whereas resident training has lagged behind. The objective of this study was to evaluate our institutional experience with resident participation in thoracic robotic surgery cases since the initiation of our program. METHODS: The first 100 robotic thoracic surgery cases at our institution were retrospectively reviewed and categorized into three sequential cohorts. Procedure type, patient and operative characteristics, level of resident participation (primary surgeon [PS] or assistant), and postoperative variables were evaluated. RESULTS: Of the first 100 cases, 38% were lung resections, 23% were esophageal operations, and 20% were sympathectomies. The distribution of cases changed over time with the proportion of pulmonary resections significantly increasing. Patient age (P < 0.05), body mass index (P = not significant [NS]), and comorbidities (P = NS) increased over time. Resident participation as PS increased from 33%-59% between the early and late cohorts (P < 0.05). A subset analysis of the 20 lobectomies (7 attending PS, 13 residents) showed similar patient characteristics (P = NS): age (67 versus 69), body mass index (29.5 versus 26.1), and American Society of Anesthesiologists category (2.8 versus 2.8). Operative and postoperative characteristics were also similar (P = NS) regardless of PS: operative time (260 versus 249 min), estimated blood loss (187 versus 203 mL), and length of stay (4.8 versus 4.7 d). CONCLUSIONS: Residents can participate as the PS in a variety of thoracic operations during the implementation of a robotics program. Operative time, estimated blood loss, and length of stay were similar regardless of level of resident participation.

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.

Intravitreal aflibercept for treatment-resistant neovascular age-related macular degeneration.

OBJECTIVE: To assess the effectiveness of intravitreal aflibercept in patients with neovascular age-related macular degeneration (AMD) previously resistant to treatment with other anti-vascular endothelial growth factor agents. DESIGN: Prospective, open-label, noncontrolled, registered clinical trial. PARTICIPANTS: Forty-nine patients with treatment-resistant neovascular AMD. INTERVENTION: A dose of 2 mg intravitreal aflibercept was administered as 3 initial loading doses every 4 weeks (week 0, week 4, and week 8), followed by further injections every 8 weeks (weeks 16 and 24) across a 24-week period in total. All patients underwent a complete ophthalmic examination, including measurement of Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), intraocular pressure assessment, adverse event monitoring, and spectral-domain optical coherence tomography at every visit. Baseline fluorescein angiography and indocyanine green angiography also were performed. MAIN OUTCOME MEASURES: Outcomes assessed included proportions of patients with a gain or loss of more than 5 ETDRS letters and a decrease or increase in central retinal thickness (CRT) of more than 150 µm at week 24 compared with baseline, change in mean BCVA and CRT between baseline and week 24, and descriptive safety data. RESULTS: The BCVA improved and CRT was reduced significantly at all follow-up visits compared with baseline (P < 0.001), with a mean improvement of 6.9 letters of BCVA and a decrease of 89.4 µm in CRT at week 24. Spacing of injections from every 4 weeks to 8 weeks resulted in an increase of 37.4 µm in CRT (P < 0.001); however, this was not correlated with a significant change in vision. There was 1 (2%) patient who lost more than 5 ETDRS letters, and 27 (55%) patients who gained more than 5 letters. Two (4%) patients had a more than 150 µm increase in CRT at week 24, and 10 (20%) patients showed a decrease in CRT of more than 150 µm. CONCLUSIONS: Intravitreal aflibercept is effective in previously treatment-resistant neovascular AMD. Further follow-up is required to determine whether these improvements can be maintained.

Injections in the back of the eye: The why, the what and when to worry.

BACKGROUND: Many Australians, particularly the elderly, suffer from eye diseases that require treatment with regular injections given into the eye. These injections can result in complications, some of which can be vision threatening. OBJECTIVE: To summarise some of the more common reasons for intraocular injection, as well as some common and/or more serious complications of intraocular injection that might present to general practitioners. DISCUSSION: Intraocular injection is an increasingly common means of treatment for a range of eye conditions. Serious complications, although rare, often require acute intervention to achieve the best outcomes, and timely referral of patients with worrying symptoms is important to achieve optimum patient care.

Lesion area progression in eyes with neovascular age-related macular degeneration treated using a proactive or a reactive regimen.

BACKGROUND: To compare the change in lesion area over 4 years of follow-up in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a proactive or a reactive regimen in routine clinical practice. METHODS: This was a multicentre, retrospective comparative study. Totally, 202 treatment-naïve nAMD eyes (183 patients) received anti-VEGF therapy according to a proactive (n = 105) or reactive (n = 97) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had baseline fluorescein angiography and annual optical coherence tomography (OCT) imaging. Two masked graders independently delineated the lesion's margins from serial OCT images and growth rates were calculated. RESULTS: At baseline, the mean [SD] lesion area was 7.24 [5.6] mm2 in the proactive group and 6.33 [4.8] mm2 in the reactive group respectively (p = 0.22). After four years of treatment, the mean [SD] lesion area in the proactive group was 5.16 [4.5] mm2 showing a significant reduction compared to the baseline (p < 0.001). By contrast, the mean [SD] lesion area kept expanding in the reactive group during the follow-up and was 9.24 [6.0] mm2 at four years (p < 0.001). The lesion area at 4 years was significantly influenced by treatment regimen, baseline lesion area, and proportion of visits with active lesions. CONCLUSIONS: Eyes treated using a reactive strategy had an increased lesion area and worse visual outcomes at 4 years. By contrast, the proactive regimen was associated with fewer recurrences of active disease, shrinkage of the lesion area, and better vision at four years.

Saffron therapy for the ongoing treatment of age-related macular degeneration.

OBJECTIVE: To assess the long-term efficacy and safety of oral saffron, a natural antioxidant, in treating mild/moderate age-related macular degeneration (AMD). METHODS AND ANALYSIS: Open-label, extension trial of 93 adults (>50 years) with mild/moderate AMD and vision >20/70 Snellen equivalent in at least 1 eye. Exclusion criteria included confounding visual lesions or significant gastrointestinal disease impairing absorption.Participants were given oral saffron supplementation (20 mg/day) for 12 months. Those already consuming Age-Related Eye Diseases Study (AREDS) supplements or equivalent maintained these.Primary outcomes included changes in multifocal electroretinogram (mfERG) response density and latency, and changes in best-corrected visual acuity (BCVA). Secondary outcomes included safety outcomes, changes in mfERG and BCVA among participants on AREDS supplements and changes in microperimetry. RESULTS: At 12 months, mean mfERG response density was significantly higher in rings 1, 2 and overall (p<0.001 for all) but not in rings 3-6, and there was no difference in response between those taking AREDS supplements and those not (p>0.05). Mean mfERG latency was not significantly different in any of rings 1-6 or overall (p>0.05 for all), again with no difference between those taking AREDS supplements or not (p>0.05). Mean BCVA was 1.6 letters worse (p<0.05) with no difference between those on AREDS supplements or not, and this may have been related to cataract progression. No saffron-related serious adverse events were detected. CONCLUSION: Saffron supplementation modestly improved mfERG responses in participants with AMD, including those using AREDS supplements. Given the chronic nature of AMD, longer-term supplementation may produce greater benefits.

Comparative assessment of subretinal hyper-reflective material in patients treated with brolucizumab versus aflibercept in HAWK and HARRIER.

PURPOSE: Post hoc analysis of the phase III HAWK and HARRIER studies to compare the reductions in subretinal hyper-reflective material (SHRM) thickness following brolucizumab 6 mg or aflibercept 2 mg treatment and to assess SHRM thickness and thickness variability as a potential biomarker of visual outcomes in patients with neovascular age-related macular degeneration (nAMD). METHODS: Optical coherence tomography images from the brolucizumab (n=700) and aflibercept (n=696) arms were analysed for the maximum SHRM thickness across the macula over 96 weeks. In a pooled treatment-agnostic analysis, the effect of week 12 SHRM thickness and SHRM thickness variability on best-corrected visual acuity (BCVA) through week 96 were also assessed. RESULTS: Brolucizumab was associated with numerically higher percentage reductions from baseline in SHRM thickness versus aflibercept in all patients (week 96: 54.4% vs 47.6%, respectively) and also in the matched subgroups with disease activity at week 16 (week 96: 51.6% vs 33.8%, respectively). In eyes with lower SHRM measurements at week 12, mean BCVA gains from baseline were higher at week 96 (<200 µm, +6.47 Early Treatment Diabetic Retinopathy Study letters; ≥200 µm, +3.10 letters). Eyes with the lowest SHRM thickness variability from week 12 to week 96 showed the greatest mean BCVA gains from baseline (week 96: <12 µm, +7.42 letters; >71 µm, -2.95 letters). CONCLUSIONS: In HAWK and HARRIER, greater reductions in maximum SHRM thickness from baseline were observed with brolucizumab compared with aflibercept. Furthermore, the data suggest that SHRM thickness postloading and SHRM thickness variability over time are biomarkers for visual outcomes in patients with nAMD.

Dexamethasone intravitreal implant in diabetic macular oedema refractory to anti-vascular endothelial growth factors: the AUSSIEDEX study.

AIM: To evaluate effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX) monotherapy in the AUSSIEDEX study non-responder subgroup, defined by diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: This prospective, open-label, observational, real-world study included pseudophakic and phakic (scheduled for cataract surgery) eyes that did not achieve a ≥5-letter best corrected visual acuity (BCVA) gain and/or clinically significant central subfield retinal thickness (CRT) improvement after 3-6 anti-VEGF injections for DME (N=143 eyes), regardless of baseline BCVA and CRT. After an initial DEX injection (baseline visit), reinjection was permitted at ≥16-week intervals. PRIMARY ENDPOINTS: changes in mean BCVA and CRT from baseline to week 52. Safety assessments included adverse events. RESULTS: Of 143 eyes, 53 (37.1%) and 89 (62.2%) switched to DEX after 3-6 (early) and >6 (late) anti-VEGF injections, respectively; 1 (0.7%) had missing information. With 2.3 injections (mean) over 52 weeks, the change in mean BCVA from a baseline of 57.8 letters was not significant at week 52. Mean CRT improved significantly from a baseline of 417.8 µm at week 52 (mean change -60.9 µm; p<0.001). Outcomes were similar in eyes switched to DEX early and late. No unexpected adverse events were reported; no filtration surgeries were required. CONCLUSION: To date, AUSSIEDEX is the largest prospective, real-world study of DEX monotherapy for treatment-naïve or anti-VEGF-refractory DME. Following early or late switch from anti-VEGF agents, DEX significantly improved anatomic outcomes at 52 weeks without new safety concerns, supporting use in anti-VEGF-refractory DME. TRIAL REGISTRATION NUMBER: NCT02731911.

Improving Communication Skills: A Roadmap for Humanistic Health Care.

This article outlines frameworks that enable health care providers to take steps to improve their health care communication skills, including not only outward-facing conversational tools but also personal awareness. Such awareness includes recognition of bias and emotional reactions, their behavioral consequences, and how to intervene when necessary. The authors describe the intrinsic and extrinsic motivators to improving communication skills, followed by a review of foundational communication microskills and suggestions on how to improve them through the perspectives of the clinician as a self-learner, the clinician with external coaching, and the administrator/leader.