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.

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.

Management of macular oedema due to retinal vein occlusion: An evidence-based systematic review and meta-analysis.

BACKGROUND: Central retinal vein occlusion and branch retinal vein occlusion are common causes of visual loss due to associated macular oedema. The aim of this review was to assess the effectiveness of interventions improving vision and treating macular oedema in central retinal vein occlusion and branch retinal vein occlusion. METHODS: Medical search engines and clinical trial registries were systematically searched. Randomised clinical trials with ≥90 eyes and real-world outcome studies with ≥100 eyes each with ≥6 months follow-up were included. RESULTS: There were 11 randomised controlled trials evaluating treatments for central retinal vein occlusion which met the inclusion criteria and 10 for branch retinal vein occlusion. There were 10 real world outcome studies of central retinal vein occlusion and 5 real world outcome studies of branch retinal vein occlusion. Meta-analysis was performed on studies that met the defined inclusion criteria. Main outcomes were change in visual acuity at 6-, 12-, 24- and 36 months by treatment. CONCLUSIONS: Intravitreal anti-vascular endothelial derived growth factor is recommended as first line treatment over intravitreal corticosteroid due to its effectiveness and lower rate of ocular adverse events. Best outcomes are achieved when intravitreal treatment is started early. Macular laser may have an adjunctive role in branch retina vein occlusion but not central retinal vein occlusion.

Update on Retinal Vein Occlusion.

Retinal vein occlusion represents the second leading cause of retinal vascular disorders, with a uniform sex distribution worldwide. A thorough evaluation of cardiovascular risk factors is required to correct possible comorbidities. The diagnosis and management of retinal vein occlusion have changed tremendously in the last 30 years, but the assessment of retinal ischemia at baseline and during follow-up examinations remains crucial. New imaging techniques have shed light on the pathophysiology of the disease and laser treatment, once the only therapeutic option, is now only one of the possible approaches with antivascular endothelial growth factors and steroid injections being preferred in most cases. Nowadays long-term outcomes are better than those achievable 20 years ago and yet, many new therapeutic options are under development, including new intravitreal drugs and gene therapy. Despite this, some cases still develop sight-threatening complications deserving a more aggressive (sometimes surgical) approach. The purpose of this comprehensive review is to reappraise some old but still valid concepts and to integrate them with new research and clinical data. The work will provide an overview of the disease's pathophysiology, natural history, and clinical features along with a detailed discussion on the advantages of multimodal imaging and of the different treatment strategies with the aim of providing retina specialists with the most updated knowledge in the field.

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.

Role of anti-vascular endothelial growth factor in the management of non-proliferative diabetic retinopathy without centre-involving diabetic macular oedema: a meta-analysis of trials.

This systematic review and meta-analysis investigated the impact of anti-vascular endothelial growth factor (VEGF) treatment in management of eyes with non-proliferative diabetic retinopathy (NPDR) without centre involving diabetic macular oedema (CI-DMO). We searched multiple databases for all randomised clinical trials (RCTs) that evaluated anti-VEGF treatment versus observation in eyes with NPDR without CI-DMO. Data was collected for six outcomes (best corrected visual acuity (BCVA) improvement, diabetic retinopathy severity score (DRSS), central subfield thickness, progression to vision threatening complications (VTCs), ocular adverse events and quality of life measures). Risk of bias was assessed using Cochrane risk-of-bias tool for randomised trials (RoB 2) and certainty of evidence was assessed using Grade of Recommendations, Assessment, Development and Evaluation (GRADE). We identified a total of 2 unique RCTs that compared aflibercept and sham to treat a total of 811 eyes. For BCVA change, there was a small, clinically insignificant benefit for aflibercept treatment at year 2 (MD 0.70, 95% CI 0.02-1.38, GRADE rating: MODERATE). DRSS demonstrated a statistically significant improvement with aflibercept use at year 2 (RR 3.76, 95% CI 2.75-5.13, GRADE rating: MODERATE). VTCs were significantly less in aflibercept arm at year 2 (RR 0.30, 95% CI 0.23-0.40, GRADE rating: MODERATE). In conclusion, aflibercept treatment versus observation in eyes with NPDR without CI-DMO can result in reduced risk of development of VTCs and regression of DRSS score over 2 years. Future trials are needed to increase the precision of the treatment effect and to provide data on quality-of-life metrics.PROSPERO Registration: CRD42021288608.

Dexamethasone intravitreal implant in treatment-naïve diabetic macular oedema: findings from the prospective, multicentre, AUSSIEDEX study.

AIM: To evaluate the effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX; Ozurdex) monotherapy in the patient subgroup of the AUSSIEDEX study with treatment-naïve diabetic macular oedema (DME). METHODS: The open-label, prospective, phase 4, real-world study included pseudophakic eyes and phakic eyes scheduled for cataract surgery that were treatment-naïve or non-responsive to antivascular endothelial growth factors. No eyes were excluded based on baseline best-corrected visual acuity (BCVA) or central subfield retinal thickness (CRT). After the initial DEX injection at the baseline visit, reinjection was permitted at ≥16-week intervals. Week-16 and week-52 visits were mandatory. Primary endpoints were changes in mean BCVA and CRT from baseline to 52 weeks. RESULTS: Of 200 eyes enrolled in the AUSSIEDEX study, 57 were treatment-naïve. Baseline mean BCVA was 58.8 letters and baseline mean CRT was 418.6 µm; changes in mean BCVA and CRT from baseline to 52 weeks in this subgroup were 3.4 letters (p=0.042) and -89.6 µm (p<0.001), respectively, with a mean 2.5 injections. The change in mean CRT from baseline was -55.8 µm at week 16 (p<0.001). The most common adverse event was increased intraocular pressure (IOP), with 20.0% of eyes requiring IOP-lowering medication. One patient was discontinued due to increased IOP. No eyes required filtration surgery. No serious, treatment-related ocular adverse events were reported. CONCLUSION: In this largest prospective, real-world study of DEX monotherapy for DME to date, DEX significantly improved CRT and BCVA at 52 weeks in treatment-naïve eyes, without new safety concerns, supporting DEX use in treatment-naïve DME. TRIAL REGISTRATION NUMBER: NCT02731911.

Vitrectomized vs non-vitrectomized eyes in DEX implant treatment for DMO-Is there any difference? the VITDEX study.

OBJECTIVE: We aimed to compare visual and anatomical outcome in vitrectomized and non-vitrectomized eyes treated with dexamethasone (DEX) implant due to diabetic macular oedema (DMO). DESIGN: Multicenter, retrospective, interventional study. PARTICIPANTS: 236 eyes from 234 patients with DMO with or without previous vitrectomy performed with follow-up of 12 months. METHODS: Records were reviewed for cases of DMO treated with DEX implant in vitrectomized and not vitrectomized eyes. Best corrected visual acuity (BCVA), central subfoveal thickness (CST), and intraocular pressure (IOP) were recorded at baseline and 12 months after treatment with DEX implants. Correlations between vitreous status and visual and anatomical outcome, as well as safety profile were analysed. MAIN OUTCOME MEASURES: BCVA and CST over follow-up period. SECONDARY OUTCOMES: cataract rate formation, intraocular pressure increase, number of implants needed. RESULTS: The non-vitrectomized group included 130 eyes (55.1%), the vitrectomized group included 106 eyes (44.9%). The groups were well balanced for age and gender (p = 0.540, and p = 0.053, respectively). Both groups showed statistically significant improvement in BCVA and CST (for all groups: p < 0.001). There was no significant difference between the groups in terms of change in vision (p = 0.89) and anatomy (p = 0.65). The mean number of DEX implants given during follow-up was 3.5 in both groups, and there was no significant difference between the groups (p = 0.81). CONCLUSION: We demonstrated similar anatomical and functional efficacy of DEX implant in non-vitrectomized and vitrectomized eyes. Its efficacy was not influenced by full vitrectomy for diabetic retinopathy complications. Safety profile was well balanced between groups.

Five-year outcomes of eyes initially enrolled in the 2-year BEVORDEX trial of bevacizumab or dexamethasone implants for diabetic macular oedema.

BACKGROUND: The BEVORDEX trial compared outcomes of eyes with diabetic macular oedema (DMO) randomised to receive either intravitreal dexamethasone (DEX-) implant or bevacizumab over 2 years. We assessed long-term efficacy and safety outcomes 5 years from enrolment. METHODS: Patients received standard clinical care after they finished the study. Their files were reviewed for visual and anatomical outcomes, post-trial treatments and complications. RESULTS: Three-year and five-year data were available for 82% and 59% of eyes enrolled in the BEVORDEX study, respectively. Visual acuity gains at end of trial were generally lost by both treatment groups at 5 years but the macular thickness did not change from end of trial to 5 years. A similar proportion of eyes from each treatment group gained ≥10 letters at 5 years from enrolment in the BEVORDEX trial.Eyes that were initially randomised to the DEX-implant group had significantly fewer treatments but were more likely to develop proliferative diabetic retinopathy (PDR) over the 5-year period compared with eyes initially randomised to bevacizumab. The proportion of eyes that had cataract surgery by 5 years was similar between initial treatment groups. CONCLUSIONS: Eyes in the BEVORDEX trial had similar 5-year rates of cataract surgery, however, more eyes converted to PDR in the group initially treated with DEX-implant. Eyes that were initially treated for 2 years with either intravitreal DEX-implant of bevacizumab followed by standard of care had similar visual and anatomical outcomes at 5 years.

Polypoidal Choroidal Vasculopathy Based on Non-ICGA Criteria in White Patients With Neovascular Age-Related Macular Degeneration.

PURPOSE: To determine prevalence of probable polypoidal choroidal vasculopathy (PCV) among White patients with neovascular age-related macular degeneration (nAMD) using non-indocyanine green angiography (ICGA) criteria DESIGN: Multicenter, multinational, retrospective, cross-sectional study. METHODS: A total of 208 treatment-naive eyes from Hispanic and non-Hispanic White individuals diagnosed with nAMD were included. All underwent color fundus photography (CFP), optical coherence tomography (OCT), and fluorescein angiography (FFA). De-identified images of study eyes were sent to 2 groups of graders. Group 1 reviewed CFP, OCT, and FFA to confirm nAMD diagnosis. Group 2 reviewed CFP and OCT to determine highly suggestive features for PCV. Probable PCV diagnosis defined as the presence of ≥2 of 4 highly suggestive features for PCV: notched or fibrovascular pigment epithelial detachment (PED) on CFP, sharply-peaked PED, notched PED, and hyperreflective ring on OCT. RESULTS: Eleven eyes were excluded because of poor image quality (6) or non-nAMD diagnosis (5). Of 197 eligible eyes (197 patients), the mean age (SD) was 78.8 years (8.9), 44.2% were men, 26.4% were Hispanic, and 73.6% were non-Hispanic White individuals; 41.1%, 23.4%, 9.1%, and 2.5% had ≥1, ≥2, ≥3, and 4 highly suggestive features. Results showed that 23.4% (95% CI, 17.6%-29.9%) had probable PCV diagnosis. Predominantly occult CNV was more frequently found in probable PCV than nAMD subgroup (84.8% vs 64.9%, P = .01). Hispanic White individuals had a lower prevalence of probable PCV than non-Hispanic White individuals (9.6% vs 28.2%, P = .006) CONCLUSIONS: These findings suggest that probable PCV occurs between 17.6% and 29.9% in White individuals with nAMD, and more commonly in non-Hispanic than in Hispanic White individuals.

One-year real-world outcomes of bevacizumab for the treatment of macular oedema secondary to retinal vein occlusion.

BACKGROUND: Bevacizumab is the only agent that many people can afford, yet there are only limited data on whether it improves macular oedema (MO) secondary to retinal vein occlusion (RVO) in real-world clinical practice. Here we studied 12-month real-world treatment outcomes of bevacizumab for RVO-related MO. METHODS: This was a multicentre, observational study analysing 12-month data from the Fight Retinal Blindness! (FRB) database. We studied treatment-naïve eyes with MO secondary to RVO commencing bevacizumab therapy between June 2009 and June 2019. Visual acuity (VA) and central subfield thickness (CST) were measured at baseline, 6 and 12 months. The primary outcome was a change in VA from baseline to 12 months. RESULTS: Two hundred and twenty treatment naive eyes were analyzed. The baseline VA for BRVO was better than CRVO (55.8 vs. 42.6 LogMAR letters) and this gap widened over the 12-month period, with a 12-month VA change of +14.0 (95% CI 11.1, 16.8) letters for BRVO and + 11.9 (95% CI 6.4, 17.4) for CRVO. The mean CST at baseline was 511 µm for BRVO and 627 µm for CRVO, falling at 12 months by -155 µm (-190, -121) in BRVO and -198 µm (-252, -145) in CRVO. The median number of injections for BRVO and CRVO completers was 7 (5, 9). CONCLUSIONS: Bevacizumab can be an effective treatment of RVO-MO in a real-world setting with outcomes approaching those reported by the seminal clinical trials. The functional and anatomical outcomes of intravitreal therapy were better for BRVO than CRVO.

Characterization of Poor Visual Outcomes of Diabetic Macular Edema: The Fight Retinal Blindness! Project.

PURPOSE: To investigate the incidence, characteristics, and baseline predictors of poor visual outcomes in eyes with diabetic macular edema (DME) receiving intravitreal therapy in routine clinical practice. DESIGN: Observational study. PARTICIPANTS: Treatment-naïve eyes starting intravitreal therapy for DME between 2014 and 2018 tracked in the Fight Retinal Blindness! registry. We examined 2 groups with poor visual outcomes: (1) those with sustained vision loss of > 10 letters from baseline without recovery of visual acuity (VA); and (2) those with a VA of < 55 letters at 2 years. Respective controls were eyes that did not experience poor visual outcomes. METHODS: Kaplan-Meier curves analyzed the proportion of eyes that experienced poor outcomes. Cox proportional hazards models evaluated the potential baseline predictors of poor outcomes. MAIN OUTCOME MEASURES: The proportion of eyes that experienced poor visual outcomes within 2 years of treatment initiation and its baseline predictors. RESULTS: The proportion of eyes with sustained VA of ≥ 10 letter loss was 14% at 2 years; 16% of eyes had VA of ≤ 55 letters 2 years after starting intravitreal therapy. Initial treatment with intravitreal corticosteroid was independently associated with a higher incidence of ≥ 10 letter loss (hazard ratio [HR], 3.21; 95% confidence interval [CI], 1.60-6.44; P < 0.01). No improvement in the VA at 3 months after starting treatment was associated with ≥ 10 letter loss (HR, 6.81; 95% CI, 4.11-11.27; P < 0.01) and VA of ≤ 55 letters at 2 years (HR, 4.28; 95% CI, 2.66-6.89; P < 0.01). The other factors related to higher risk of VA of ≤ 55 letters were older age (HR, 1.02 per year; 95% CI, 1-1.04; P = 0.04) and poor baseline VA (HR, 0.68 per 5 letters; 95% CI, 0.65-0.72, P < 0.001). CONCLUSIONS: Fourteen percent of eyes managed with intravitreal therapy in routine clinical care experienced ≥ 10 letter loss and 16% had VA of ≤55 letters 2 years after starting the treatment for DME. The identification of the incidence and predictors of poor outcomes provides a more accurate assessment of the potential benefit from intravitreal therapy.

Reactivation of Multifocal Choroiditis Associated with Treatment in Latent Tuberculosis.

Tuberculosis (TB) causes significant morbidity and mortality worldwide. Ocular manifestations of TB can lead to severe and sight-threatening complications. Initiating treatment in ocular TB with anti-tubercular therapy (ATT) may be necessary to prevent long-term visual complications. We present a case of the reactivation of bilateral multifocal choroiditis (MFC) in a patient with latent TB after commencing ATT. An asymptomatic 36-year-old Indian male was referred to an ophthalmologist with extensive inactive bilateral MFC close to his fovea despite no previous medical or ocular history. Latent TB was subsequently diagnosed via TB specific antigens and antibodies. After a period of stable observation without evidence of active eye or systemic disease, the patient was commenced on quadruple ATT with the aim of reducing the risk of visual loss with the MFC. However, after commencing treatment, MFC reactivation was observed. This settled with the addition of high-dose oral prednisone. The steroid was slowly weaned and ceased with the cessation of ATT. There have been no further episodes of active choroiditis since treatment was ceased. TB is a significant cause of mortality worldwide, and ocular manifestations can cause severe and sight-threatening complications in active and latent TB. The treatment of TB, however, may lead to further complications. We present the case of a visually asymptomatic patient with latent TB, with before and after fundal images, demonstrating the reactivation of the MFC after commencing ATT.

12-month outcomes of ranibizumab versus aflibercept for macular oedema in central retinal vein occlusion: data from the FRB! registry.

PURPOSE: To compare 12-month treatment outcomes of eyes receiving aflibercept or ranibizumab for macular oedema secondary to central retinal vein occlusion (CRVO) in routine clinical practice. METHODS: 296 treatment-naïve eyes receiving either aflibercept (171 eyes, 2 mg) or ranibizumab (125 eyes, 0.5 mg) for macular oedema secondary to CRVO were recruited retrospectively from centres using the prospectively designed FRB! registry. The primary outcome measure was the mean change in LogMAR letter scores of visual acuity (VA). Secondary outcomes included change in central subfield thickness (CST), injections and visits, time to first grading of inactivity, switching and non-completion from baseline to 12 months. RESULTS: Baseline VA (SD) was somewhat better in aflibercept- versus ranibizumab-treated eyes (42.5 ± 25.5 letters versus 36.9 ± 26 letters; p = 0.07) with similar CST (614 (240) µm versus 616 (234) µm: p = 0.95). The 12-month adjusted mean (95%CI) VA change was +16.6 (12.9, 20.4) letters for aflibercept versus +9.8 (5.5, 14.1) letters for ranibizumab (p = 0.001). The mean (95%CI) adjusted change in CST was significantly greater in aflibercept- versus ranibizumab-treated eyes: -304 (-276, -333) µm versus -252 (-220, -282) µm (p < 0.001). Both groups had a median (Q1, Q3) of 7 (5, 9) injections and 10 (8,13) visits. Aflibercept-treated eyes became inactive sooner than ranibizumab (p = 0.02). Switching occurred more commonly from ranibizumab (26 eyes, 21%) than from aflibercept (9 eyes, 5%) (p < 0.001). CONCLUSION: Both aflibercept and ranibizumab improved VA and reduced CST in eyes with CRVO in routine clinical practice, with aflibercept showing significantly greater improvements in this comparative analysis.

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.

Twelve-month outcomes of ranibizumab versus aflibercept for macular oedema in branch retinal vein occlusion: data from the FRB! registry.

BACKGROUND/AIMS: To compare the efficacy of ranibizumab (0.5 mg) with aflibercept (2 mg) in the treatment of cystoid macular oedema due to branch retinal vein occlusion (BRVO) over 12 months. METHODS: A multicentre, international, database observational study recruited 322 eyes initiating therapy in real-world practice over 5 years. The main outcome measure was mean change in EDTRS letter scores of visual acuity (VA). Secondary outcomes included anatomic outcomes, percentage of eyes with VA >6/12 (70 letters), number of injections and visits, time to first inactivity, switching or non-completion. RESULTS: Generalised mixed effect models demonstrated that mean (95% CI) adjusted 12-month VA changes for ranibizumab and aflibercept were similar (+10.8 (8.2 to 13.4) vs +10.9 (8.3 to 13.5) letters, respectively, p=0.59). The mean adjusted change in central subfield thickness (CST) was greater for aflibercept than ranibizumab (-170 (-153 to -187) µm vs -147 (-130 to -164) µm, respectively, p=0.001). The overall median (Q1, Q3) of 7 (4, 8) injections and 9 (7, 11) visits was similar between treatment groups. First grading of inactivity occurred sooner with aflibercept (p=0.01). Switching was more common from ranibizumab (37 eyes, 23%) than from aflibercept (17 eyes, 11%; p=0.002). CONCLUSION: Visual outcomes at 12 months in this direct comparison of ranibizumab and aflibercept for BRVO in real-world practice were generally good and similar for the 2 drugs, despite a greater effect of aflibercept on CST and time to first grading of inactivity.

Initial observation or treatment for diabetic macular oedema with good visual acuity: two-year outcomes comparison in routine clinical practice: data from the Fight Retinal Blindness! Registry.

PURPOSE: To compare visual acuity (VA) change at 24 months in eyes with clinically significant DME (CSDME) and good VA initially treated versus initially observed in routine clinical practice. METHODS: Retrospective analysis of treatment-naïve eyes with CSDME and good VA (baseline VA ≥ 79 letters), with at least 24 months of follow-up and initially managed with treatment (intravitreal treatment and/or macular laser) or observation with possible treatment after 4 months that were tracked in a prospectively designed observational registry. RESULTS: We identified 150 eligible eyes (98 initially observed, 52 initially treated) of 130 patients. The proportion of eyes with at least a 5-letter VA loss at 24 months was not significantly different between the groups: 65% with initial observation and 42% with initial treatment (p = 0.39). However, initially observed eyes were more likely to have a 10-letter VA loss at 24 months (OR = 4.6, p = 0.022). Most of eyes in the initial observation group received at least one treatment (an intravitreal injection in 66% and macular laser in 20%) during the 24-month period. CONCLUSIONS: The risk of 5 letters loss was similar between both management groups. However, initially observed eyes were more at risk of developing moderate visual loss and more than 80% of them required treatment over 24 months.

Retinal findings in glomerulonephritis.

The complement system is part of the innate immune system activated by three distinct pathways: classical, lectin and alternative. It is also involved in retinal development and homoeostasis. Dense deposit disease is a rare renal disease associated with mutations in Complement factor H and overactivity of the alternative complement pathway. As well as glomerulonephritis, many affected individuals have retinal drusen and may be at risk of vision loss due to macular atrophy or choroidal neovascularisation. We discuss the reclassification of dense deposit disease as a type of C3 glomerulonephropathy, and hypothesise on the mechanisms of retinal abnormalities. Drusen have also been described in individuals with other types of glomerulonephritis involving abnormalities of the classical (membranoproliferative glomerulonephritis type 1) or lectin (IgA nephropathy, lupus nephritis) complement pathways. Although drusen are found in abnormalities of all three complement pathways, the age at onset, aetiology, and the threat to vision differs. This review describes drusen and other retinal abnormalities associated with the glomerulonephritides due to abnormal activation in each of the three complement activation pathways, and provides the first report of drusen occurring in a patient with the recently reclassified C3 glomerulonephritis with homozygous variant V62I in complement factor H. Optometric management of young patients presenting with retinal drusen is discussed, and complement-based therapies for visual loss are reviewed.

Patient-reported outcomes from a phase IV study of aflibercept in patients with refractory retinal vein occlusions.

PURPOSE: To determine the patient-centered effectiveness of switching patients with persistent macular edema due to retinal vein occlusion (RVO) to aflibercept using the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25). MATERIALS AND METHODS: Prospective study of eyes with persistent cystoid macular edema due to RVO despite regular treatment with bevacizumab or ranibizumab switched to aflibercept. Three loading doses of intravitreal aflibercept were administered every 4 weeks and thereafter every 8 weeks until week 48. Vision-related quality of life (VRQoL) using NEI-VFQ-25 was measured at baseline, 24 weeks, and 48 weeks following the switch. Baseline scores were compared to week 24 and 48 using paired t-test. Relationship between best-corrected visual acuity (BCVA) in the study eye and the NEI-VFQ-25 composite and subscale scores was investigated. RESULTS: Eighteen patients with RVO were enrolled in the study with a mean age of 70.3 ± 8.6 years. The mean change in BCVA and central macular thickness (CMT) from baseline to 48 weeks was +20.6 ± 5.2 Early Treatment of Diabetic Retinopathy Score letters and -109.2 ± 82.8 µm, respectively. VRQoL improved significantly, with an increase of mean NEI-VFQ composite score of 11.5 ± 9.5; the corresponding improvements in near and distant activities were 13.3 ± 19.4 and 8.4 ± 10.4, respectively (P < 0.001 for both). Logistic regression analysis demonstrated that BCVA gain of >15 letters and CMT < 300 µm at the end of the study predicted a higher change in VFQ-25. CONCLUSION: Switching eyes with persistent macular edema due to RVO to aflibercept resulted in significant improvement in visual function and patient satisfaction.