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.

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.

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.

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.

Long-term outcomes of anti-VEGF treatment of retinal vein occlusion.

BACKGROUND/OBJECTIVES: To analyze the long-term outcomes of eyes with retinal vein occlusion (RVO) 8 years after commencing treatment with anti-vascular endothelial growth factor (VEGF) agents. SUBJECTS/METHODS: Retrospective, multicentre study of 221 eyes diagnosed with RVO, which were commenced on anti-VEGF therapy between 2009 and 2011. VA and CRT were recorded at baseline and at subsequent annual time points. The mean number of injections administered each year and the incidence of adverse events were recorded. RESULTS: Of a total of 221 eyes which commenced treatment with anti-VEGF agents for RVO, 95 were diagnosed with BRVO and 126 with CRVO. 8-year data were available for 94 eyes (43%). The mean age of patients was 65.1 ± 12.0 years. Mean VA improved from baseline by 16.9 letters, (57.8-74.7 letters), (P < 0.001). For BRVO eyes, mean VA improved from 60.5 to 74.8 letters (p < 0.001) and for CRVO eyes from 52.0 to 66.4 letters (p < 0.001). In all RVO eyes, there was a reduction in mean CRT from 501.0 to 249.1 µm; in BRVO eyes from 472.4 to 284.7 µm and in CRVO eyes from 533.9 to 267.5 µm. In the 8th year after starting treatment, eyes with RVO were receiving a mean of four injections. CONCLUSION: Good long-term outcomes of VEGF inhibition for eyes with RVO were found in this study. Patients maintained a gain of 3-lines of vision 8-years after the commencing therapy. This encouraging result contrasts with long-term studies of patients with neovascular age-related macular degeneration, where initial gains are lost over time.

Efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy in Japanese participants of HAWK.

PURPOSE: To compare the efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy (PCV) over 96 weeks in the HAWK study. DESIGN: HAWK was a global, 2-year, randomised, double-masked, multicentre phase III trial in participants with neovascular age-related macular degeneration. METHODS: Of the Japanese participants with PCV, 39 received brolucizumab 6 mg and 30 received aflibercept 2 mg. After 3 monthly loading doses, brolucizumab-treated eyes received an injection every 12 weeks (q12w) but were adjusted to q8w if disease activity was detected. Aflibercept-treated eyes received fixed q8w dosing. Mean change in best-corrected visual acuity (BCVA), the proportion of participants on q12w, retinal thickness, retinal fluid changes and safety were assessed to Week 96. RESULTS: Mean change in BCVA (early treatment diabetic retinopathy study (ETDRS) letters) from baseline to week 48/week 96 was+10.4/+11.4 for brolucizumab and +11.6/+11.1 for aflibercept. For brolucizumab-treated eyes, the probability of only q12w dosing after loading through week 48 was 76%, and 68% through week 96. Fluid resolution was greater with brolucizumab than aflibercept: respective proportions of eyes with intraretinal fluid and/or subretinal fluid were 7.7% and 30% at week 48% and 12.8% and 16.7% at week 96. Brolucizumab exhibited an overall well-tolerated safety profile despite a higher rate of intraocular inflammation compared with aflibercept. CONCLUSION: In Japanese eyes with PCV, brolucizumab q12w/q8w monotherapy resulted in robust and consistent BCVA gains that were comparable to q8w aflibercept dosing. Anatomical outcomes favoured brolucizumab over aflibercept, with 76% of brolucizumab participants maintained on q12w dosing after loading to week 48.

Endophthalmitis: Changes in Presentation, Management and the Role of Early Vitrectomy.

Endophthalmitis is a sight-threatening condition, and its timely and appropriate management is essential in preventing permanent vision loss. Recent changes in clinical practice in endophthalmitis and advances in modern vitreoretinal surgery may limit the applicability of established randomised clinical trial evidence to current management. This review discusses the epidemiology, pathophysiology, changing patient presentation, diagnosis and advances in the management of endophthalmitis, presenting the existing literature on this topic and results from Sydney Eye Hospital.

Predictors of Visual Acuity After Treatment of Neovascular Age-Related Macular Degeneration - Current Perspectives.

Visual acuity is a key outcome measure in the treatment of neovascular age-related macular degeneration (nAMD) using anti-vascular endothelial growth factor agents. Large variations in visual responses between individuals within clinical trials and real-world studies may relate to underlying differences in patient and treatment factors. Most notably, a better baseline visual acuity, younger age and smaller choroidal neovascularization lesion size have been strongly associated with achieving better visual outcomes. In addition, there is emerging evidence for other roles including genetic factors and anatomical variables such as fluid status. Apart from patient-related factors, treatments that favor a higher number of injections tend to provide better visual outcomes. Overall, the identification of predictive factors does not currently play an essential role in the clinical management of patients with nAMD. However, they have allowed for the understanding that early detection, timely management and close monitoring of the disease are required to achieve optimal visual outcomes. Further investigation into predictive factors alongside the development of novel therapeutic agents may one day provide a means to accurately predict patient outcomes. Treatment regimens that offer flexible dosing patterns such as the treat-and-extend strategy currently provide a degree of personalization during treatment.

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.

Diet and risk of visual impairment: a review of dietary factors and risk of common causes of visual impairment.

Age-related macular degeneration, diabetic retinopathy, cataract, and glaucoma remain the leading causes of visual impairment in developed nations, resulting in a substantial treatment burden on sufferers and health care systems. Despite significant advances in diagnostic testing and therapeutics, population-based strategies to reduce the burden of these diseases remain limited. However, there is some evidence that these diseases may share overlapping risk factors, particularly in regard to dietary intake and antioxidant status, and it is thus possible that dietary modification may reduce both the prevalence and severity of these conditions. In particular, dietary intake of green leafy vegetables, hyperglycemia/glycemia index, and omega-3 fatty acid intake, as well as overall dietary patterns, may affect risk of one or more of these conditions. In this review, we analyse the evidence for dietary intake and the association with these conditions, and provide insights into possible modifications that may thus simultaneously reduce the risk of visual impairment from multiple causes, including improving dietary intake of green leafy vegetables and reducing dietary glycemic index, both of which have been associated with a decreased risk of multiple causes of visual impairment.

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.

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.

To Treat or Not to Treat: Management Options for Symptomatic Vitreous Floaters.

Vitreous floaters are a common cause for presentation to ophthalmologists, and may significantly affect visual function. In the absence of some more serious underlying pathology such as uveitis, many patients may not experience significant persistent visual impairment from floaters. For some patients, the symptomatic effects of floaters may persist. For these patients, treatment options are available, of which the most commonly reported is vitrectomy. Other treatment modalities have also become more common, notably YAG vitreolysis. Selection of appropriate patients for surgery is often difficult, in part due to the relative lack of objective outcomes with which to measure both visual impairment and improvement post-procedure. Although well-tolerated, vitrectomy does carry with it risks, including iatrogenic retinal breaks, retinal detachment, and in phakic patients, subsequent cataract formation. Techniques such as small gauge vitrectomy, intraoperative examination and treatment of breaks or other worrying lesions, and careful consideration of the need for posterior vitreous detachment induction may help limit the incidence of these adverse events. For other treatment options such as YAG vitreolysis, research and clinical experience remain more limited, and as such the long-term efficacy and risks of these therapies are still unclear. Here, we review the evidence surrounding the role of vitrectomy and YAG vitreolysis in the treatment of vitreous floaters and potential means to minimize therapeutic complications.

Burden Of Treatment Among Patients Undergoing Intravitreal Injections For Diabetic Macular Oedema In Australia.

AIM: The incidence and prevalence of diabetes mellitus (DM) in Australia is increasing. Thus, it is essential that practitioners appreciate the impending effect that increasing incidence of diabetes has on patients and the wider community. Accordingly, this study examines the humanistic burden of intravitreal injections for the treatment of diabetic macular oedema (DMO) among several health variables. METHODS: Survey data from a representative sample of Australian adults undergoing treatment for DMO were examined. Respondents participated via an online survey recruited by means of a national online consumer panel and the New South Wales and Victorian Diabetes Foundations. The online survey included questions relating to the humanistic burden of disease, such as the emotional and physical impact of intravitreal injection therapy; the practical impacts of injection therapy; and to identify potential improvements to treatment regimens. RESULTS: Sixty-five participants took part in the online survey. Of these, 49% had their most recent injection <1 month prior to completing the survey. The mean age was 52.5 years, with the majority of patients in full-time work. A substantial proportion of participants had several comorbidities, with a significantly high Charlson comorbidity index of 2.7. Participants reported the main burden of DMO care was the direct cost of medical treatment and the time burden demanded upon their carers. Results suggest that the overall burden is significant for those with diabetes and increases as additional complications of diabetes occur. CONCLUSION: These results suggest that treatment strategies for DMO should consider clinical, humanistic and economic burden and patients should be educated on the roles of complications in disease outcomes. Less frequent treatment regimens could also reduce the economic burden and assist in decreasing the effect on health care resources, relevant to the escalation in the prevalence of diabetes.

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.

Five-year outcomes of retinal vein occlusion treated with vascular endothelial growth factor inhibitors.

PURPOSE: Report 5-year outcomes of patients receiving anti-vascular endothelial growth factor (VEGF) for the treatment of macular oedema secondary to retinal vein occlusion (RVO. METHODS: Retrospective review of eyes with RVO which initiated anti-VEGF treatment. Data including age, gender, visual acuity (VA) and injection numbers were obtained from medical records. Optical coherence tomography scans were graded for presence or absence of macular oedema and central foveal thickness (CFT). Macular perfusion was assessed on fundus fluorescein angiography by masked graders. RESULTS: 68 eyes (31 branch RVO, BRVO; 35 central RVO, CRVO and 2 hemi-RVO) with 5 years of follow-up after initiation of anti-VEGF treatment. Mean change in VA at 5 years was + 9.6 ± 21.6 letters among CRVO eyes and + 14.2 ± 15.6 letters among eyes with BRVO (p=0.001). Vision of 20/40 or better was achieved in 65 % of treated eyes. The proportion of eyes with a three-line improvement of vision (15 letters) at 5 years was 22 %. Mean CFT decreased by 257.6 ± 249.8 µm in eyes with CRVO and 145.6 ± 143.3 µm in eyes with BRVO. CONCLUSION: The results confirm good long-term outcomes can be achieved with anti-VEGF therapy for RVO.

Long-term outcomes of switching to aflibercept for treatment-resistant neovascular age-related macular degeneration.

PURPOSE: To report 4-year outcomes following the switch to aflibercept in treatment-resistant neovascular age-related macular degeneration (nAMD). METHODS: In this prospective, open-label, non-controlled, clinical trial, 49 patients with treatment-resistant nAMD received 2 mg intravitreal aflibercept as three loading doses every 4 weeks, followed by injections every 8 weeks for the first 48 weeks, then an individualized regimen for a further 36 months, following previous treatment with ranibizumab and/or bevacizumab. Outcome measures included best-corrected visual acuity (BCVA), central retinal thickness (CRT), pigment epithelial detachment (PED) height and geographic atrophy (GA) surface area. RESULTS: Of the 49 patients who were initially recruited, data from 39 eyes of 39 patients were available at 48-month follow-up. Mean age was 76.7 ± 7.2 years. Over the 48 months, these eyes received a mean of 32.1 ± 5.6 injections. The mean BCVA improved significantly following 12 months of treatment (4.9 ± 9.0 ETDRS letters, p < 0.001); however, this was not maintained and was similar to baseline after 48 months (mean difference -0.4 ± 13.3 letters between baseline and 48 months, p < 0.001). The reduction in CRT from baseline was 170.3 ± 143.3 µm (p < 0.001) with absence of macular fluid in 56% of the 39 eyes at the end of month 48. PED height reduced by a mean 77.5 ± 20.0 µm, and geographic atrophy increased by a mean of 4.1 ± 3.4 mm2 (p < 0.01) over the 48 months. CONCLUSION: Aflibercept is an effective alternative therapy for treatment-resistant nAMD. Good anatomical and stable functional responses are achievable with continued therapy. The lack of continued visual improvement may be representative of GA progression, reflecting the progression of late-stage nAMD in these patients.

Early Pars Plana Vitrectomy for Treatment of Acute Infective Endophthalmitis.

PURPOSE: To evaluate the efficacy and safety of early pars plana vitrectomy (PPV) for the treatment of acute infective endophthalmitis, and identify prognostic factors for better visual outcome. DESIGN: Retrospective cohort study. METHODS: Consecutive patients who underwent early PPV within 72 hours of presentation for the treatment of acute infective bacterial endophthalmitis and presented to a large tertiary referral center in New South Wales, Australia, between January 2009 and December 2013 were included. Changes in best-corrected visual acuity (VA) from baseline to 1 year were examined. RESULTS: A total of 64 patients were included. The inciting events were cataract surgery (53%), intravitreal injection (36%), trabeculectomy (3%), and endogenous (3%). The mean VA improved from 3.1 logMAR (hand motion) at baseline to 1.02 (approximately 20/200) at 1 year, with 42% achieving final VA equal to or better than 0.477 logMAR (20/60) following early PPV. Positive prognostic factors were negative microbial cultures (P < 0.01) and etiology of post-cataract surgery (P < 0.01). In multivariable analyses adjusting for age and prognostic factors, patients with baseline VA of light perception and hand motion achieved greater visual gains than those with counting fingers, with gains of logMAR of -2.68, -2.09, and -0.85, respectively (P < 0.0001). CONCLUSIONS: Most patients who undergo early PPV experience substantial VA improvement. Negative microbial cultures and endophthalmitis after cataract surgery were associated with better final visual outcome. Patients with presenting VA of light perception or hand motion achieved higher visual gains than those with counting fingers, suggesting the possibility that early PPV may be beneficial in both groups.