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.

Diabetic Macular Oedema Guidelines: An Australian Perspective.

The number of people living with diabetes is expected to rise to 578 million by 2030 and to 700 million by 2045, exacting a severe socioeconomic burden on healthcare systems around the globe. This is also reflected in the increasing numbers of people with ocular complications of diabetes (namely, diabetic macular oedema (DMO) and diabetic retinopathy (DR)). In one study examining the global prevalence of DR, 35% of people with diabetes had some form of DR, 7% had PDR, 7% had DMO, and 10% were affected by these vision-threatening stages. In many regions of the world (Australia included), DR is one of the top three leading causes of vision loss amongst working age adults (20-74 years). In the management of DMO, the landmark ETDRS study demonstrated that moderate visual loss, defined as doubling of the visual angle, can be reduced by 50% or more by focal/grid laser photocoagulation. However, over the last 20 years, antivascular endothelial growth factor (VEGF) and corticosteroid therapies have emerged as alternative options for the management of DMO and provided patients with choices that have higher chances of improving vision than laser alone. In Australia, since the 2008 NHMRC guidelines, there have been significant developments in both the treatment options and treatment schedules for DMO. This working group was therefore assembled to review and address the current management options available in Australia.

Association of Dietary Nitrate and a Mediterranean Diet With Age-Related Macular Degeneration Among US Adults: The Age-Related Eye Disease Study (AREDS) and AREDS2.

Importance: Low dietary nitrate intake has previously been suggested to be a risk factor for age-related macular degeneration (AMD) progression; however, this finding has not been replicated in other cohorts or adjusted for dietary patterns. Objective: To determine whether there is an association between dietary nitrate intake and AMD progression. Design, Setting, and Participants: This cohort study analyzed data from the prospective Age-Related Eye Disease Study (AREDS) and AREDS2 randomized clinical trial cohorts and their extended follow-up studies, which were conducted in multicenter outpatient retinal practices. Participants in both trials had non-late AMD in at least 1 eye. Data were analyzed from March 1, 2020, to September 30, 2022. Exposure: Dietary nitrate intake. Main Outcomes and Measures: Association between dietary nitrate intake and development of late AMD (neovascular AMD [nAMD] or geographic atrophy [GA]) or large drusen. The interactions of dietary patterns, with common at-risk single-nucleotide polymorphisms, were also assessed. Results: In the combined AREDS/AREDS2 cohort of 7788 participants (4288 AREDS participants and 3610 AREDS2 participants [110 of whom participated in both studies]), there were 13 511 eligible eyes. The combined cohort comprised 4396 women (56%) and 3392 men (44%), and the combined mean (SD) age was 71.1 (6.6) years. Dietary nitrate intake was associated with a decreased risk of progression to late AMD in the combined AREDS/AREDS2 cohort (hazard ratio [HR], 0.77 [95% CI, 0.69-0.86] for quartile 4 vs quartile 1 of intake) and a decreased risk of GA (HR, 0.71 [95% CI, 0.61-0.83]) and nAMD (HR, 0.85 [95% CI, 0.73-0.99]). In AREDS, increased nitrate intake (quartile 4 vs quartile 1) was associated with a decreased risk of late AMD (HR, 0.77 [95% CI, 0.65-0.91]) and GA (HR, 0.80 [95% CI, 0.65-0.97]) but not nAMD; in AREDS2, there was no association between nitrate intake (quartile 4 vs quartile 1) and late AMD (HR, 0.90 [95% CI, 0.80-1.02]) or nAMD (HR, 0.93 [95% CI, 0.78-1.11]). There was a correlation between Mediterranean dietary patterns and dietary nitrate intake (r = 0.52, P < .001). Conclusions and Relevance: The findings of this cohort study suggest that dietary nitrate intake was associated with lower AMD risk. However, this association disappeared after adjusting for Mediterranean dietary patterns. These results are subject to potential bias and are hypothesis-generating in nature; therefore, they are insufficient to support new clinical recommendations. Previously described associations between dietary nitrate intake and AMD may in fact represent overall dietary patterns. Further research is needed before dietary nitrate intake can be recommended as a therapy for AMD.

Proliferative Retinopathy Associated with Repeated High-Altitude Exposure in a Patient with Sickle Cell Trait.

Broadhead Geoffrey K., Henry E. Wiley, David Peprah, Kenneth Olumba, and Alisa T. Thavikulwat. Proliferative retinopathy associated with repeated high-altitude exposure in a patient with sickle cell trait. High Alt Med Biol. 23:369-371, 2022.-Sickle cell trait (SCT), a carrier state characterized by one normal copy of the beta-globin gene (producing hemoglobin A) and one abnormal variant (producing hemoglobin S), is typically asymptomatic and very low risk for manifestations of hemoglobinopathy, including development of retinopathy. Reported cases of proliferative retinopathy in patients with SCT have occurred in the context of concurrent ocular or systemic disease. We report a case of an otherwise healthy patient with SCT who developed proliferative retinopathy requiring surgical intervention in the setting of significant exposure to high altitude through increased work hours as a flight attendant in the month leading to her presentation. Significant high-altitude exposure may contribute to development of retinopathy in patients with sickle trait. Practitioners should consider the possibility of sickle cell retinopathy in patients with sickle trait in these circumstances.

DeepLensNet: Deep Learning Automated Diagnosis and Quantitative Classification of Cataract Type and Severity.

PURPOSE: To develop deep learning models to perform automated diagnosis and quantitative classification of age-related cataract from anterior segment photographs. DESIGN: DeepLensNet was trained by applying deep learning models to the Age-Related Eye Disease Study (AREDS) dataset. PARTICIPANTS: A total of 18 999 photographs (6333 triplets) from longitudinal follow-up of 1137 eyes (576 AREDS participants). METHODS: Deep learning models were trained to detect and quantify nuclear sclerosis (NS; scale 0.9-7.1) from 45-degree slit-lamp photographs and cortical lens opacity (CLO; scale 0%-100%) and posterior subcapsular cataract (PSC; scale 0%-100%) from retroillumination photographs. DeepLensNet performance was compared with that of 14 ophthalmologists and 24 medical students. MAIN OUTCOME MEASURES: Mean squared error (MSE). RESULTS: On the full test set, mean MSE for DeepLensNet was 0.23 (standard deviation [SD], 0.01) for NS, 13.1 (SD, 1.6) for CLO, and 16.6 (SD, 2.4) for PSC. On a subset of the test set (substantially enriched for positive cases of CLO and PSC), for NS, mean MSE for DeepLensNet was 0.23 (SD, 0.02), compared with 0.98 (SD, 0.24; P = 0.000001) for the ophthalmologists and 1.24 (SD, 0.34; P = 0.000005) for the medical students. For CLO, mean MSE was 53.5 (SD, 14.8), compared with 134.9 (SD, 89.9; P = 0.003) for the ophthalmologists and 433.6 (SD, 962.1; P = 0.0007) for the medical students. For PSC, mean MSE was 171.9 (SD, 38.9), compared with 176.8 (SD, 98.0; P = 0.67) for the ophthalmologists and 398.2 (SD, 645.4; P = 0.18) for the medical students. In external validation on the Singapore Malay Eye Study (sampled to reflect the cataract severity distribution in AREDS), the MSE for DeepSeeNet was 1.27 for NS and 25.5 for PSC. CONCLUSIONS: DeepLensNet performed automated and quantitative classification of cataract severity for all 3 types of age-related cataract. For the 2 most common types (NS and CLO), the accuracy was significantly superior to that of ophthalmologists; for the least common type (PSC), it was similar. DeepLensNet may have wide potential applications in both clinical and research domains. In the future, such approaches may increase the accessibility of cataract assessment globally. The code and models are available at https://github.com/ncbi/deeplensnet.

Comparison of agents using higher dose anti-VEGF therapy for treatment-resistant neovascular age-related macular degeneration.

PURPOSE: To explore the comparative efficacy and safety of higher dose intravitreal bevacizumab, ranibizumab, or aflibercept for treatment-resistant neovascular age-related macular degeneration (nAMD). METHODS: Retrospective analysis of 37 eyes of 35 patients with treatment-resistant nAMD divided into 3 cohorts based on high-dose treatment received: 3 mg aflibercept, 0.75 mg or 1.0 mg ranibizumab, and 1.8 mg or 2.5 mg bevacizumab. The eyes were analyzed at standardized time points up to 48 months. Included eyes demonstrated active nAMD with persistent exudation on imaging for at least 6 months with at least 4 anti-VEGF injections during this time. Outcomes included change in visual acuity (VA), central retinal thickness (CRT), intraocular pressure (IOP), retinal morphology, adverse event occurrence, and yearly intravitreal injection (IVI) rate. RESULTS: There was no significant difference in VA or IOP change compared to the initiation of high-dose treatment for any agent or comparing between agents at any time point (p > 0.05). CRT improved at month 1, 3, 6, and 12 with all 3 agents (p < 0.05 for all) with a greater CRT reduction seen for ranibizumab than aflibercept at month 6 (p < 0.05), although baseline CRT was greater in the ranibizumab group than the aflibercept group (p < 0.05). Mean absolute CRT was similar at month 6 for all agents (p > 0.05). IVI rates pre- and post-conversion to higher-dose therapy were similar (1 injection per 5.7-6.4 weeks). Mean follow-up was 22.8 months. CONCLUSIONS: Higher dose therapy may achieve improved anatomic outcomes and maintain vision, but frequent injections are required to achieve this. There was no detected difference in efficacy or safety between agents.

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.

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.

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.

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.

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.

The burden of neovascular age-related macular degeneration: a patient's perspective.

PURPOSE: To quantify the burden and quality of life of patients and their caregivers in a cohort of patients with neovascular age-related macular degeneration (nAMD) in an Australian clinical setting. METHODS: A total of 103 patients undergoing anti-vascular endothelial growth factor (VEGF) therapy for nAMD were asked to complete questionnaires relating to the financial and time burdens of nAMD. RESULTS: All patients completed the questionnaires. Loss in productivity due to attendance of appointments was 4.4±1.7 hours per month, with additional time lost by caregivers. Financial strain was incurred by direct medical costs associated with intravitreal assessment and injections at an average of AU$199.2±$83.1 per month. Indirect costs incurred averaged $64.8±$79.7 per month. Qualitative indirect costs due to loss of productivity for the patient, unpaid caregivers, and loss of productivity due to premature mortality were also a considerable burden. Overall mean Visual Function Questionnaire and EuroQol 5D-3L scores were correlated with visual acuity and demonstrated patients' subjective decline in quality of vision. CONCLUSION: Management of nAMD carries a substantial burden on patients and caregivers. These results provide important information in understanding the effect of anti-VEGF therapy among patients with nAMD. Together with the quality-of-life burden on the patients, the management of nAMD has a significant societal impact.

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.

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.

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.