Intravitreal ranibizumab and dexamethasone implant injections as primary treatment of diabetic macular edema: simultaneously double protocol

PurposeTo assess the 12-month efficacy and safety of simultaneously administered intravitreal dexamethasone implant (DEX implant) and ranibizumab (simultaneous double protocol) injections in comparison with ranibizumab monotherapy as the first-line treatment of diabetic macular oedema (DMO).MethodsProspective, consecutive, clinical interventional study. Patients were randomized into two groups: 24 naive DMO patients (34 eyes) who received simultaneous double-protocol therapy and 22 DMO patients (34 eyes) who received ranibizumab monotherapy were included. Monthly ranibizumab (0.5 mg) was administered for the first 6 months and later on, an as-needed treatment basis. DEX implant injection was performed at any time during the loading dose of the three consecutive monthly injections of ranibizumab, and with as-needed reinjections of ranibizumab from 6th month onwards. Change in visual acuity was the primary efficacy endpoint. Secondary efficacy endpoints were a gain of ≥15 letters and a change in the central foveal thickness.ResultsMean BCVA increased from baseline to month 12 in the simultaneously double-protocol therapy group compared with the ranibizumab monotherapy group (21.6 versus 9.6 letters [P < 0.001]). The corresponding proportions of eyes gaining ≥15 letters were 60% versus 29.4% (P < 0.0001). Moreover, the mean reductions in the central foveal thickness were 413 versus 282 µm (P = 0.001). At 12 month, the simultaneous double-protocol therapy decreased a significant number of foveal cysts and subfoveal neuroretinal detachment compared with those by ranibizumab monotherapy.ConclusionsThe simultaneous addition of DEX implant at any time during the three monthly loading doses of ranibizumab in patients with DMO significantly improved the visual outcomes and revealed superior anatomic outcomes than those with the ranibizumab monotherapy.Subject terms: Retinal diseases, Prognosis     

Visual and anatomical outcomes following intravitreal aflibercept in eyes with recalcitrant neovascular age-related macular degeneration: 12-month results

Purpose

To describe the efficacy of intravitreal aflibercept on 12-month visual and anatomical outcomes in patients with neovascular age-related macular degeneration (AMD) recalcitrant to prior monthly intravitreal bevacizumab or ranibizumab.

Methods

Non-comparative case series of 21 eyes of 21 AMD patients with evidence of persistent exudation (intraretinal fluid/cysts, or subretinal fluid (SRF), or both) on spectral domain OCT despite ≥6 prior intravitreal 0.5 mg ranibizumab or 1.25 mg bevacizumab (mean 29.8±17.1 injections) over 31.6±17.4 months who were transitioned to aflibercept.

Results

At baseline, best-corrected visual acuity (BCVA) was 0.42±0.28 logarithm of minimum-angle of resolution (logMAR), central foveal thickness (CFT) was 329.38±102.67 μm and macular volume (MV) was 7.71±1.32 mm³. After 12 months of aflibercept (mean 10.2±1.2 injections), BCVA was 0.40±0.28 logMAR (P=0.5), CFT decreased to 292.71±91.35 μm (P=0.038) and MV improved to 7.33±1.27 mm³ (P=0.003). In a subset of 15 eyes with a persistent fibrovascular or serous pigment epithelial detachment (PED), mean baseline PED greatest basal diameter (GBD) was 2350.9±1067.6 μm and mean maximal height (MH) was 288.7±175.9 μm. At 12 months, GBD improved to 1896.3±782.3 μm (P=0.028), while MH decreased to 248.27±146.2 μm (P=0.002).

Conclusion

In patients with recalcitrant AMD, aflibercept led to anatomic improvement at 12 months, reduction in proportion of eyes with SRF and reduction in PED, while preserving visual acuity.     

Phase I/II randomized study of proton beam with anti-VEGF for exudative age-related macular degeneration: long-term results

Background/objectiveTo determine if treatment of exudative age-related macular degeneration (eAMD) using proton beam therapy (PBT) combined with intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is safe and effective long term.Subject/methodsThirty eyes with newly diagnosed eAMD were enrolled in a phase I/II prospective, sham-controlled double-masked university study. Eyes were randomized 1:1:1–24 GyE, 16 GyE or sham radiation, and treated with three initial monthly intravitreal ranibizumab or bevacizumab. Subsequent anti-VEGF reinjection was based on monthly optical coherence tomography and examination for 2 years and standard of care thereafter.ResultsA total of 23 eyes completed 2-year study follow-up, of which 16 maintained monthly follow-up. Mean best-correct visual acuity (BCVA) at 2 years was similar among treatment groups (p > 0.05). The 24 GyE group required fewer anti-VEGF injections when compared with the sham group at 2 years (4.67 ± 1.9 vs 9.67 ± 3.5; p = 0.017). Extended follow-up (mean 4 years) available in 22 eyes showed persistent reduced need for anti-VEGF therapy among eyes treated with 24 GyE compared with sham radiation (2.0 ± 1.6 vs 4.84 ± 2.4 per year, p = 0.008). New and increasing geographic atrophy (GA), noted in some eyes in all treatment groups, resulted in decreased mean BCVA from baseline for the 24 GyE group on extended follow-up (p = 0.009). Possible mild radiation retinopathy noted in 15% of eyes was not visually significant.ConclusionsInitial treatment combining PBT (24 GyE) with intravitreal anti-VEGF therapy appears to decrease the need for anti-VEGF reinjection in eyes with newly diagnosed eAMD. Radiation retinopathy risk was low and does not appear visually significant. Long-term vision was limited by GA development especially in the 24 GyE group.Subject terms: Macular degeneration, Outcomes research     

Short-term intraocular pressure trends following intravitreal ranibizumab injections for neovascular age-related macular degeneration—the role of oral acetazolamide in protecting glaucoma patients

Purpose

To determine the effect of oral acetazolamide on lowering the peak and duration of intraocular pressure (IOP) rise in glaucoma and glaucoma suspect patients, following intravitreal injection of ranibizumab for neovascular age-related macular degeneration.

Methods

The study was an open-label, parallel, randomised, controlled trial (EudraCT Number: 2010-023037-35). Twenty-four glaucoma or glaucoma suspect patients received either 500 mg acetazolamide or no treatment 60–90 min before 0.5 mg ranibizumab. The primary outcome measure was the difference in IOP immediately after injection (T0) and 5, 10, and 30 min following injection. ANCOVA was used to compare groups, adjusting for baseline IOP. The study was powered to detect a 9-mm Hg difference at T0.

Results

The IOP at T0 was 2.3 mm Hg higher in the non-treated group (mean 44.5 mm Hg, range (19–86 mm Hg)) compared with the treated group (mean 42.2 mm Hg, range (25–58 mm Hg)), but was not statistically significant after adjusting for baseline IOP (P=0.440). At 30 min, IOP was 4.9 mm Hg higher in the non-treated group (mean 20.6 mm Hg, range (11–46 mm Hg)) compared with the treated group (mean 15.7 mm Hg, range (8–21 mm Hg)). This was statistically significant after adjusting for baseline IOP (P=0.013).

Conclusions

Although the primary end points were not reached, 500 mg oral acetazolamide, 60–90 min before intravitreal injection, results in a statistically significant reduction in IOP at 3O min post injection. Prophylactic treatment may be considered as an option to minimise neuro-retinal rim damage in high-risk glaucoma patients who are most vulnerable to IOP spikes and undergoing repeated intravitreal injections of ranibizumab.     

Transitioning to intravitreal aflibercept following a previous treat-and-extend dosing regimen in neovascular age-related macular degeneration: 24-month results

Purpose:

To evaluate frequency of injections, visual and anatomical outcomes of neovascular age-related macular degeneration (nAMD) patients transitioned to intravitreal aflibercept after failure to extend treatment interval beyond 8 weeks with prior intravitreal bevacizumab or ranibizumab.

Methods:

Retrospective review of patients with nAMD switched to aflibercept following ≥6 prior intravitreal ranibizumab or bevacizumab injections at 4–8-week intervals. Three monthly aflibercept injections were given followed by a treat-and-extend dosing regimen.

Results:

Twenty-one eyes of 18 patients who had received a mean of 23.8±18.8 (mean±SD; range 6–62) prior ranibizumab or bevacizumab injections were included. Over a mean follow-up of 24 months after the transition, 9.2±2.9 (range 4–21) aflibercept injections were required. Interval between aflibercept injections increased to 57.3 days (range 35–133 days), as compared with 37±6.1 days (range 29–54 days) with the prior agents (P=0.01). Mean best-corrected visual acuity was preserved (0.42±0.31 vs 0.42±0.23 logMAR; P=0.2). Mean OCT central subfoveal thickness (292.1±83.2 μm to 283.6±78.6 μm; P=0.4) and mean macular volume (7.9±0.95 mm³ to 7.67±0.94 mm³; P=0.16) remained stable.

Conclusion:

Patients requiring treatment more frequently than every 8 weeks with ranibizumab and bevacizumab were transitioned to >8-week treatment interval with aflibercept while maintaining the anatomic and visual gains.     

Effectiveness and safety of ranibizumab in patients with central retinal vein occlusion: results from the real-world,global, LUMINOUS study

ObjectiveTo evaluate the effectiveness, treatment patterns and long-term safety of ranibizumab 0.5 mg in treatment-naïve patients with central retinal vein occlusion (CRVO) in a real-world setting.MethodsLUMINOUS, a 5-year, global, prospective, multicentre, multi-indication, observational, open-label study, recruited treatment naïve or prior treated patients who were treated as per the local ranibizumab label. Here, we report the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), treatment exposure over year (Y) 1 and 5-year safety in treatment-naïve CRVO patients.ResultsAt baseline, the mean age of treatment-naïve CRVO patients (n = 327) was 68.9 years, with a mean (Standard deviation [SD]) VA of 40.6 (23.9) letters. At Y1, patients (n = 144) had a mean (SD) VA gain from baseline of 10.8 (19.66) letters, with a mean (SD) of 5.4 (2.65) ranibizumab injections. Patients demonstrated mean (SD) VA gains of 2.7 (19.35), 11.6 (20.56), 13.9 (18.08), 11.1 (18.46) and 8.2 (24.86) letters with 1, 2–3, 4–5, 6–8 and >8 ranibizumab injections, respectively. Mean (SD) VA gains at Y1 in patients receiving loading (67.4%) and no loading dose (32.6%) was 11.9 (20.42) and 8.4 (17.99) letters, respectively. Over five years, the incidence of ocular/non-ocular adverse events (AEs) and serious AEs was 11.3%/8.6% and 1.2%/6.7%, respectively.ConclusionsThese results demonstrate the effectiveness of ranibizumab in treatment-naïve CRVO patients at Y1 with clinically meaningful VA gains and no new safety findings over five years. These findings may help inform routine practice and enable better clinical management to achieve optimal visual outcomes.Subject terms: Retinal diseases, Clinical pharmacology     

Morphometric analysis of corneal endothelium after intravitreal ranibizumab (Lucentis) in age-related macular degeneration treatment

PurposeTo determine the effect of intravitreal injection of 0.5 mg ranibizumab on the corneal endothelium in patients with age-related macular degeneration (AMD).MethodsObservational, prospective case series pilot study. Twenty-six eyes of 26 consecutive patients with AMD were evaluated. All participants received one monthly intravitreal injections of 0.5 mg ranibizumab for three consecutive months. The follow-up period was 6 months. Central corneal specular microscopy was performed before injection and at 7 days and 6 months after the first intravitreal injection. The endothelial cell density, coefficient of variation of cell size, and percentage of hexagonal cells were analyzed and the central corneal thickness was measured.ResultsThere were no significant differences in the endothelial cell densities, coefficients of variation of cell size and percentages of hexagonal cells before injection and at 7 days and 6 months after the first intravitreal ranibizumab injection (P > 0.5). There was also no significant difference in central corneal thickness measurements through the follow-up period (P > 0.5).ConclusionsRepeated intravitreal injections of 0.5 mg ranibizumab do not seem to cause substantial changes in the corneal endothelium.     

Residual edema evaluation with ranibizumab 0.5?mg and 2.0?mg formulations for diabetic macular edema (REEF study)

Purpose

To compare the efficacy of ranibizumab 0.5-mg and 2.0-mg intravitreal injections for persistent diabetic macular edema (DME) previously treated with bevacizumab.

Methods

In all, 43 patients with residual center-involved DME following intravitreal bevacizumab were included in this 12-month prospective, nonrandomized, multicenter study. Enrolled patients received three monthly ranibizumab 0.5-mg injections. At month 3, patients with residual macular edema switched to three monthly injections of ranibizumab 2.0-mg. Assessments included monthly visual acuity and spectral-domain optical coherence tomography.

Results

Mean visual acuity improved by +6.4 letters at month 3 and +8.8 letters at month 6. Mean central subfield thickness (CST) decreased by –113 μm at month 3 and –165 μm at month 6. Before enrollment, 29/43 (67.4%) patients showed <10% CST reduction following monthly bevacizumab treatment. After three monthly ranibizumab 0.5-mg injections, 22/29 (75.9%) patients showed >10% reduction in CST, whereas 6 showed <10% reduction. Of these six, three (50%) showed >10% reduction in CST after switching to three monthly ranibizumab 2.0-mg doses. No serious adverse events were observed to month 6.

Conclusion

Ranibizumab 0.5-mg or 2.0-mg may improve visual and anatomic outcomes in patients with DME who demonstrated minimal or no response to bevacizumab therapy. Moreover, increased dosage of ranibizumab (2.0-mg) may provide additional benefit over ranibizumab 0.5-mg in some patients. However, 2.0-mg ranibizumab is not currently commercially licensed or available.     

Predictive factors for exudation of quiescent choroidal neovessels detected by OCT angiography in the fellow eyes of eyes treated for a neovascular age-related macular degeneration

BackgroundTo identify predictive factors for exudation for quiescent choroidal neovessels (qCNV) in the fellow eyes of eyes treated for a neovascular age-related macular degeneration (AMD).MethodsProspective observational study. One hundred and forty-four contralateral eyes of 144 patients treated for wet AMD were analysed. At a baseline visit, multimodal imaging including dye angiographies and optical coherence tomography angiography (OCT-A) was performed in order to detect qCNV. Patients were followed up for 12 months with a monthly assessment. The manifestation of any type of exudation (either intra- or subretinal fluid or hyperreflective subretinal material) was monitored.ResultsThe prevalence of qCNV in the treatment-naive eyes was 15.9% with an incidence over a 12-month period of 2.8%. In total, 40.7% of the overall neovessels remained stable with no sign of exudation, while 59.3% presented some fluid during the follow-up. A statistically significant relationship was established for the following variables preceding the exudation: increase in central macular thickness (OR = 116; 95% CI [4.74; 50530] p = 0.038), increase in pigment epithelial detachment height (OR = 1.76; 95% CI [1.17; 3.18] p = 0.021) and width (OR = 1.53; 95% CI [1.12; 2.62] p = 0.042), increase in neovessels’ surface on OCT-A (OR = 6.32; 95% CI [1.62; 51.0] p = 0.033), emergence of a branching pattern (OR = 7.50; 95% CI[1.37; 61.5] p = 0.032) and appearance of a hypointense halo surrounding the lesion (OR = 10.00; 95% CI [1.41; 206] p = 0.048).ConclusionsThe risk of exudation in the treatment-naive fellow eyes of eyes treated for neovascular AMD was notably increased in the presence of qCNV. The biomarkers identified will help to detect their activation in order to ensure prompt antiangiogenic therapy.Subject terms: Risk factors, Tomography     

Intravitreal aflibercept treatment in eyes with exudative age-related macular degeneration following prior treatment with intravitreal ranibizumab

Background:

To investigate visual and anatomical outcomes in eyes with exudative age-related macular degeneration treated with intravitreal aflibercept following prior treatment with intravitreal ranibizumab.

Materials and Methods:

Retrospective, single-center study of 192 eyes treated with 0.5 mg intravitreal ranibizumab every 4 weeks for three consecutive doses followed by a variable dose schedule. After more than 12 months of ranibizumab treatment, eyes that required ranibizumab injections at 4-week or 6-week intervals were switched to aflibercept therapy.

Results:

After 12–69 months (42 months ± 18 months, mean ± standard deviation [SD]) of treatment with intravitreal ranibizumab, 80 eyes were changed to 2 mg intravitreal aflibercept treatment with follow-up after 12–18 months (16 months ± 1 month, mean ± SD). Thirty-nine eyes had persistent macular fluid after treatment with ranibizumab. Mean logMAR visual acuity (VA) in eyes treated with ranibizumab changed by − 0.089 ± 0.310 (mean ± SD; P = 0.0003), which correlates to an approximate gain of 4.5 letters. The number of eyes with macular fluid decreased from 39 to 23 after aflibercept treatment. Mean logMAR VA in eyes with intraretinal macular fluid treated with aflibercept changed by −0.079 ± 0.134 (mean ± SD; P = 0.006), which correlates to an approximate gain of 4 letters. Mean logMAR VA in eyes with submacular fluid was not significantly different after aflibercept treatment.

Conclusion:

Eyes with persistent intraretinal macular fluid had visual and anatomic response after changing from ranibizumab to aflibercept treatment.     

Pilot study to evaLuate the role of high-dose rAnibizumab 2.0 mg in the management of neovascular age-related macular degeneration in patients with perSistent/recurrenT macular fluid <30 days following treatment with intravitreal anti-VEGF therapy (the LAST Study)

Purpose

To determine the efficacy of intravitreal ranibizumab 2.0 mg in patients with recalcitrant neovascular age-related macular degeneration (AMD).

Methods

This single-masked, randomized, prospective, pilot study enrolled patients with subfoveal neovascular AMD. All study eyes had persistent subretinal (SRF) or intraretinal fluid (IRF) on spectral-domain optical coherence tomography (SD-OCT) <30 days following at least 6 monthly intravitreal injections of ranibizumab or bevacizumab. Patients were randomized 2 : 1 to receive either ranibizumab 2.0 or 0.5 mg. Following three-loading treatments 4-weeks apart, both groups were treated using a ‘treat and extend'' regimen guided by eye-tracked SD-OCT through month 12. The primary end point was the mean change in best-corrected visual acuity (BCVA) at month 6.

Results

Nine eyes of 9 patients (mean age±SD, 82.0±5.8 years) were enrolled. Seven eyes received ranibizumab 2.0 mg and two eyes received 0.5 mg. Owing to the small number of patients enrolled, no statistical comparison could be made between the two dosages. At month 6, the mean improvement in BCVA was +6.1±3.7 (W=0, P<0.001) ETDRS letters and +2.0 ETDRS letters in the 2.0 and 0.5 mg groups, respectively. In the 2.0 mg group, there was a statistically significant decline in central foveal thickness, SRF and maximum pigment epithelial detachment height at 6 months compared with baseline. No adverse events were reported in either group.

Conclusion

Ranibizumab 2.0 mg has the potential to maintain or improve BCVA in some patients with persistent or recurrent SRF or IRF secondary to neovascular AMD despite prior monthly intravitreal anti-vascular endothelial growth factor therapy with the standard dose.     

Effects of ranibizumab on human corneal endothelial cells

PurposeThis study aims to evaluate corneal endothelial changes occurring over a 3-month period after intravitreal injections of ranibizumab in patients with wet age-related macular degeneration.MethodsThis is a prospective case series. A total of 29 patients (29 eyes) received a 0.5-mg intravitreal injection of ranibizumab. Specular microscopy, including measurement of central corneal thickness and endothelial cell count, was performed on each patient prior to and after completing three intravitreal injections.ResultsAll patients received three intravitreal injections and were followed up for a mean of 3 months. There was no significant change in corneal thickness (p = 0.32) or endothelial cell density (p = 0.38) after ranibizumab injections.ConclusionIntravitreal ranibizumab injections (0.5 mg) have no harmful effects on corneal endothelial cells.     

Long-term follow-up of primary silicone oil tamponade for retinal detachment secondary to macular hole in highly myopic eyes: a prognostic factor analysis

PurposeTo investigate the risk factors associated with retinal detachment recurrence after first vitrectomy in high myopic eyes with macular hole retinal detachment (MHRD).MethodsPatients with high myopic eyes with MHRD who underwent pars plana vitrectomy and silicone oil (SO) tamponade with a follow-up period more than 12 months and more than 3 months after SO removal were included in this retrospective study. Logistic regression was performed to determine the risk factors associated with retinal re-detachment.ResultsA total of 45 eyes from 43 patients were included in this study (11 male and 34 female patients). The retinal re-detachment rate after the first removal of silicon oil was 35.5% (16/45) in a mean postoperative follow-up time of 35.64 ± 32.94 months. Complete macular atrophy on fundus photography (odds ratio (OR) = 17.021, 95% confidence interval (95% CI): 2.218–130.609, p = 0.006) was a risk factor for MHRD after SO removal, while internal limiting membrane (ILM) peeling (OR = 0.091, 95% CI: 0.013–0.633, p = 0.015) and duration of SO tamponade (OR = 0.667, 95% CI: 0.454–0.980, p = 0.039) were protective factors.ConclusionFor high myopic eyes with MHRD, complete macular atrophy was a significant risk factor for retinal re-detachment after silicon oil removal. ILM peeling and the duration of silicon oil tamponade were protective factors.Subject terms: Retinal diseases, Risk factors     

Microperimetry and mfERG as functional measurements in diabetic macular oedema undergoing intravitreal ranibizumab treatment

PurposeTo evaluate Microperimetry (MP) and multifocal electroretinogram (mfERG) as whole-macula functional markers of treatment response in naive diabetic macular oedema (DMO) patients undergoing ranibizumab treatment.MethodsAn exploratory sub-analysis of a prospective study ({"type":"clinical-trial","attrs":{"text":"NCT01947881","term_id":"NCT01947881"}}NCT01947881-CHARTRES). Patients received three monthly ranibizumab injections (loading dose) followed by pro re nata (PRN) regimen during 1 year. At baseline, during and after treatment (Months 0, 3, 6 and 12), subjects were tested using BCVA, OCT, MP and mfERG. MP was performed in the central 12°, and retinal sensitivity was measured overall (mean sensitivity (MS)), and in three concentric rings (R1–R3). mfERG P1 amplitude and implicit time were measured over six concentric rings (R1–R6).ResultsThirty-two eyes were included. MP mean and rings sensitivity were significantly lower in DMO (p < 0.001). After loading dose, a significant improvement in retina sensitivity was observed, particularly in good BCVA responders (MS = +2.28 dB; R1 = +2.33 dB, R2 = +2.20 dB, R3 = +2.25 dB; p = 0.049). Overall retinal sensitivity was significantly correlated with BCVA improvement (r = 0.54; p = 0.026) and inversely correlated with OCT central subfield thickness improvement (r = −0.39; p = 0.026). mfERG amplitude and implicit time were also lower in DMO (p < 0.011). An improvement of mfERG P1 amplitude and implicit time in R1 was noted in good responders after ranibizumab loading dose (+16.49 nV/deg²; p = 0.013 and −0.005 ms; p = 0.048, respectively). When changing to PRN treatment regimen, BCVA was maintained during the 12 months of follow-up but worsening of the visual function was detected by MP and mfERG.ConclusionsMicroperimetry and mfERG were able to demonstrate DMO functional improvement after treatment loading dose, as well as early visual changes when treatment regimen was switched to PRN.Subject terms: Predictive markers, Retinal diseases     

Maternal smoking as an independent risk factor for the development of severe retinopathy of prematurity in very preterm infants

Background/objectivesRetinopathy of prematurity (ROP) is a severe neonatal complication potentially leading to visual impairment and blindness. Known risk factors include preterm birth, low birth weight and respiratory support. Limited and contradictory data exist on the risk of maternal smoking during pregnancy on the development of ROP. This study aims to investigate smoking as an independent risk factor for the development of severe ROP (≥stage 3).Subjects/methodsThis is a single centre retrospective case-control study of prospectively collected clinical data of infants born before 32 weeks of gestation between 2001 and 2012 at a tertiary care university hospital. The association between maternal smoking during pregnancy and the development of severe ROP was analyzed by multivariate logistic regression.ResultsIn total, n = 751 infants born < 32 weeks of gestation were included in this study. In total, 52.9% (n = 397) were diagnosed with ROP and 10.8% (n = 81) developed ROP ≥ stage 3. In total, 8.4% (n = 63) mothers presented with a history of smoking during pregnancy, which was associated to a higher rate of ROP (OR 2.59, 95% CI 1.10–6.12). Low gestational age, low birth weight and prolonged respiratory support were confirmed as independent risk factors for the development of severe ROP.ConclusionsTo date, this is the largest study evaluating the effect of maternal smoking on the development of ROP. Maternal smoking during pregnancy is identified as an independent risk factor for the development of severe ROP in preterm infants born < 32 weeks of gestation.Subject terms: Retinal diseases, Risk factors, Outcomes research     

Impact of injection frequency on 5-year real-world visual acuity outcomes of aflibercept therapy for neovascular age-related macular degeneration

BackgroundTo evaluate the impact of injection frequency on yearly visual outcomes of patients treated with intravitreal aflibercept for neovascular age-related macular degeneration (nAMD) over a period of 5 years in a tertiary ophthalmic centre.DesignSingle centre, retrospective cohort study.ParticipantsConsecutive treatment-naive nAMD patients initiated on aflibercept injections 5 years ago.MethodsThe Moorfields OpenEyes database was searched for consecutive patients who were initiated on intravitreal aflibercept for nAMD in 2013–14 and the visual acuity (VA) in Early Diabetic Retinopathy Study (ETDRS) letters and injection records per year were recorded for a period of 5 years. Analyses of the whole cohort and a sub-sample of 5-year completers were done. The cohort was further grouped into Group A (on continuous treatment), Group B (early cessation of treatment) and Group C (interrupted treatment) to evaluate the relation between treatment frequency and visual outcomes.Main outcome measuresThe primary end point was change in VA at 5 years; secondary outcomes included proportion of eyes that gained or maintained VA, number of injections received and the effect of treatment frequency.ResultsData were collected on 468 patients (512 eyes). Sixty-six percent of the patients completed 5-year follow-up. The mean age of the whole cohort was 79.5 ± 8.5 years and the mean baseline VA was 58.3 ± 15.4 letters. Amongst the completers, final VA change was −2.9 (SD 23.4) ETDRS letters and the cumulative number of injections over 5 years was 24.2 (10.6). Group A had three letter gain and received significantly higher cumulative number of injections over 5 years than Group B and C (31.8, 14.6 and 18.4 respectively, p = 0.001). After adjusting for age and baseline VA, on average, final VA was +8.0 letters higher in the ≥20 injections group than the <20 group (p = 0.001).ConclusionsAflibercept therapy results in sustained good visual outcome over 5 years in neovascular AMD eyes when early and persistent treatment is given.Subject terms: Macular degeneration, Vision disorders     

Postoperative severe visual impairment: surgical outcome of 165 patients with orbital tumours in the muscle cone

ObjectiveThis study aimed to evaluate the risk factors of postoperative severe vision impairment (PSVI) for a primary orbital tumour in the muscle cone.MethodsA retrospective analysis of the patients who underwent orbitotomy for primary intraconal tumours at the Tianjin Medical University Eye Hospital from January 2010 to December 2015.ResultsA total of 165 cases of orbitotomy for primary orbital tumours in the muscle cone were included in the study. Postoperatively, 12 cases with vision acuity ≤20/400 or ≥4 rows of vision decline and without any corrected effect were analysed as PSVI, including no light perception (NLP) for 3 cases. The multivariate logistic regression indicated that the tumour in orbital apex (P = 0.048, OR = 4.912, 95% CI: 1.011–23.866), severe optic nerve displacement (P = 0.030, OR = 6.007, 95% CI: 1.184–30.473) and intraoperative tight adhesion (P = 0.003, OR = 12.031, 95% CI: 2.282–63.441) were the independent risk factors for PSVI.ConclusionsThe incidence of PSVI for the intraconal tumour was 7.3%, and the incidence of NLP was 1.8%. The tumour in orbital apex, severe optic nerve displacement and intraoperative tight adhesion were independent risk factors for PSVI.Subject terms: Risk factors, Vision disorders, Surgery     

Continued anti-VEGF treatment does not prevent recurrences in eyes with stable neovascular age-related macular degeneration using a treat-and-extend regimen: a retrospective case series

BackgroundThe continuation of anti-vascular endothelial growth factor (anti-VEGF) treatment after achieving stability in patients with neovascular age-related macular degeneration has generally been advocated. In our own patients, we thought to assess whether continued anti-VEGF treatment is capable of preventing recurrences.MethodsIn this retrospective observational case series, patients with stable disease either opted to continue treatment every 12–14 weeks (Group 1) or stopped treatment with subsequent follow-up visits every 8–12 weeks (Group 2).ResultsOf the 103 eyes of 103 patients achieving stability, 49 eyes continued treatment (Group 1), whereas treatment was stopped in 54 eyes undergoing regular follow-up (Group 2). Recurrent disease was observed in 21 (42.9%) and 33 (61.1%) cases in Group 1 and Group 2, respectively (p = 0.08). Time between achieving stable disease and recurrence was comparable between Group 1 and Group 2 (11.1 ± 8.2 months vs. 9.2 ± 6.7 months; p = 0.43). The number of visits between achieving stability and disease recurrence was similar, but not the number of injections (3.5 ± 2.0 vs. 0.2 ± 0.4; p < 0.001).ConclusionsContinuing anti-VEGF therapy after achieving functional and morphological stability every 12–14 weeks does not prevent recurrences. Patients deserve to be informed of a potential lifetime risk of recurrences, even under continued therapy.Subject terms: Macular degeneration, Retinal diseases     

Reproducibility of qualitative assessment of drusen volume in eyes with age related macular degeneration

BackgroundAlthough an optical coherence tomography (OCT)-derived central drusen volume ≥0.03 mm³ has been found to be a risk factor for progression to late age-related macular degeneration (AMD), this parameter is not currently available on most OCT devices or acquisition protocols. The purpose of this study was to evaluate the ability of human graders to qualitatively assess drusen volume by inspection of OCT B-scans.Methods100 subjects (200 eyes) from the Amish Eye Study diagnosed with early or intermediate AMD underwent OCT imaging with both Cirrus OCT and Spectralis OCT. Drusen volume was automatically computed from the Cirrus OCT volumes using the Cirrus Advanced RPE Analysis software. Spectralis volume scans were reviewed by two independent, masked graders who were asked to determine whether the central drusen volume was ≥0.03 mm³. Cohen’s kappa coefficients were computed to assess the agreement.ResultsAfter excluding 11 eyes with poor image quality and 5 eyes used for training of the graders, the remaining 184 eyes were included in this analysis. The agreement between the graders and the automated evaluation of drusen volume by the Cirrus OCT was excellent with K = 0.88 for grader 1 and K = 0.82 for grader 2. The agreement between graders was also excellent with a K = 0.88.ConclusionsThe presence of a high central drusen volume can be assessed reliably by qualitative inspection of OCT B-scans. This approach may be useful in the assessment of risk for progression to late AMD.Subject terms: Macular degeneration, Eye diseases