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Aim To evaluate the role of intravitreal aflibercept injection as a treatment for eyes with chronic central serous chorioretinopathy (CSCR). Methods This prospective pilot study enrolled 12 patients with chronic CSCR who received a 6-month treatment regimen of intravitreal aflibercept. Patients were followed with monthly Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) and spectral domain optical coherence tomography (SD-OCT) with enhanced depth imaging. Results All patients were men between 29 and 64 years (median 55). Subfoveal fluid was present on OCT for a median duration of 6 months (range 4–29 months) prior to treatment. Baseline BCVA ranged from 20/25 to 20/160 (median 20/50) with a mean of 62 (SD=13) ETDRS letters. No patients experienced serious ocular or systemic adverse events over the course of the study. Post-treatment BCVA ranged from 20/20 to 20/200 (median 20/40), with a mean of 64 (SD=16) ETDRS letters (p=0.56). At baseline, three patients (25%) had BCVA of ≥20/40 versus seven patients (58%) at the conclusion of the study. Two patients gained at least 15 ETDRS letters and no patients lost more than 15 ETDRS letters. Six of 12 patients (50%) had complete resolution of subfoveal fluid. Mean central macular thickness decreased from 400 µm (SD=104 µm) to 306 µm (SD=94 µm) (p=0.03), and mean subfoveal fluid decreased from 159 µm (SD=93 µm) to 49 µm (SD=68 µm) (p=0.02). Mean choroidal thickness decreased from 307 µm (SD=72 µm) to 263 µm (SD=63 µm) (p=0.0003). Conclusions Intravitreal aflibercept was well tolerated over a 6-month treatment course for chronic CSCR. No change was observed in visual acuity metrics. Anatomic trends may suggest some morphological activity, but larger controlled trials are needed. Trial registration number NCT01710332

PurposeTo evaluate the association between subfoveal choroidal thickness (SFCT) and branch retinal vein occlusion (BRVO) eyes treated with antivascular endothelial growth factor (anti-VEGF) therapy.MethodsRetrospective cohort study of treatment naïve BRVO eyes treated with 3 monthly anti-VEGF injections. All patients received enhanced depth imaging spectral-domain optical coherence tomography scans to determine SFCT and central macular thickness (CMT). Baseline predictors (particularly SFCT) for functional response (best-corrected visual acuity (BCVA) gain ≥2 lines) were assessed at 3 months using univariate and multivariate analyses.ResultsForty eyes from 39 patients were included. Mean baseline SFCT was higher in functional responders (240.4±73.1 µm), compared with both non-responders (193.3±63.6 µm; p=0.036) and their corresponding fellow eye (202.2±67.1 µm; p=0.022). A higher baseline SFCT (for every 100 µm increase in SFCT) was found to be a positive predictor for functional response (regression coefficient: 1.1; p=0.03) on univariate analysis but not multivariate analysis. A worse baseline BCVA (for every 0.1 logMAR increase) was a positive predictor for visual improvement with an adjusted OR of 1.30 (95% CI 1.03 to 1.63; p=0.0009) on multivariate analysis.ConclusionsPatients with BRVO with a worse initial BCVA are most likely to achieve visual improvement following anti-VEGF therapy. Additionally, baseline SFCT may also help predict which patients with BRVO have favourable visual outcomes. Patients with an initial choroidal thickness thicker than their fellow eye are more likely to have short-term visual improvement following treatment.

A 41-year-old man who had had a subarachnoid hemorrhage 10 years earlier presented with a 2-day history of blurred vision and throbbing headache. Nondilated funduscopic examination revealed multilayered hemorrhages in both eyes.

Frequent anti-vascular endothelial growth factor A (VEGF-A) injections reduce the risk of rapid and severe vision loss in patients with neovascular age-related macular degeneration (nAMD); however, due to undertreatment, many patients lose vision over time. New treatments that provide sustained suppression of VEGF-A are needed. RGX-314 (currently known as ABBV-RGX-314) is an adeno-associated virus serotype 8 vector that expresses an anti-VEGF-A antigen-binding fragment, which provides potential for continuous VEGF-A suppression after a single subretinal injection. We report results on the safety and efficacy of subretinal injection of RGX-314 in patients with nAMD. For this open-label, multiple-cohort, multicentre, phase 1/2a, dose-escalation study conducted at eight sites in the USA, we enrolled participants with nAMD aged 50–89 years who had previously been treated with anti-VEGF injections into five cohorts (with five different doses of RGX-314). To be eligible, participants had to have macular neovascularisation secondary to nAMD with subretinal or intraretinal fluid in the centre subfield, be pseudophakic (after cataract removal), and have a best-corrected visual acuity (BCVA) in the study eye between 20/63 and 20/400 for the first participant in each cohort and between 20/40 and 20/400 for others. Subretinal injection of RGX-314 was done without a pre-bleb by a wet-laboratory-trained vitreoretinal surgeon. Cohort 1 received 3 × 109 genome copies per eye, cohort 2 received 1 × 1010, and cohort 3 received 6 × 1010. Two additional dose cohorts (cohort 4: 1·6 × 1011; cohort 5: 2·5 × 1011) were added. Participants were seen 1 day and 1 week after administration of RGX-314, and then monthly for 2 years (up to week 106). The primary outcome was safety of RGX-314 delivered by subretinal injection up to week 26. This analysis includes all 42 patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT03066258. Between May 12, 2017, and May 21, 2019, we screened 110 patients for eligibility and enrolled 68. 42 participants demonstrated the required anatomic response to intravitreal ranibizumab and then received a single RGX-314 injection (dose range 3 × 109 to 2·5 × 1011 genome copies per eye) and were followed up for 2 years. There were 20 serious adverse events in 13 participants, of which one was possibly related to RGX-314: pigmentary changes in the macula with severe vision reduction 12 months after injection of RGX-314 at a dose of 2·5 × 1011 genome copies per eye. Asymptomatic pigmentary changes were seen in the inferior retinal periphery several months after subretinal injection of RGX-314 most commonly at doses of 6 × 1010 genome copies per eye or higher. There were no clinically determined immune responses or inflammation beyond that expected following routine vitrectomy. Doses of 6 × 1010 genome copies or higher resulted in sustained concentrations of RGX-314 protein in aqueous humour and stable or improved BCVA and central retinal thickness with few or no supplemental anti-VEGF-A injections in most participants. Subretinal delivery of RGX-314 was generally well tolerated with no clinically recognised immune responses. RGX-314 gene therapy provides a novel approach for sustained VEGF-A suppression in patients with nAMD that has potential to control exudation, maintain vision, and reduce treatment burden after a single administration. Results from this study informed the pivotal programme to evaluate RGX-314 in patients with nAMD. RegenxBio.

A 59-year-old patient with bilateral worsening diabetic macular edema received intravitreal injection of aflibercept (Eylea; Regeneron, Tarrytown, NY) to the left eye only. On 1-month follow-up, there was noted bilateral improvement of visual acuity and diabetic macular edema on spectral-domain optical coherence tomography imaging, reflecting bilateral effect of unilateral treatment with aflibercept. [ Ophthalmic Surg Lasers Imaging Retina. 2016;47:474–476.]

CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10. In this open-label, phase 1b/2 ( NCT03140969 ), 12-month, multicenter, multiple-dose, dose-escalation trial, six adult patients and five pediatric patients received ≤4 doses of intravitreal sepofarsen into the worse-seeing eye. The primary objective was to evaluate sepofarsen safety and tolerability via the frequency and severity of ocular adverse events (AEs); secondary objectives were to evaluate pharmacokinetics and efficacy via changes in functional outcomes. Six patients received sepofarsen 160 µg/80 µg, and five patients received sepofarsen 320 µg/160 µg. Ten of 11 (90.9%) patients developed ocular AEs in the treated eye (5/6 with 160 µg/80 µg; 5/5 with 320 µg/160 µg) versus one of 11 (9.1%) in the untreated eye; most were mild in severity and dose dependent. Eight patients developed cataracts, of which six (75.0%) were categorized as serious (2/3 with 160 µg/80 µg; 4/5 with 320 µg/160 µg), as lens replacement was required. As the 160-µg/80-µg group showed a better benefit–risk profile, higher doses were discontinued or not initiated. Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development. Intravitreal administration of the antisense oligonucleotide sepofarsen in patients with Leber congenital amaurosis type 10 showed a manageable safety profile, ocular adverse events being dose dependent, and achieved meaningful improvements of visual function.

A full-thickness macular hole (FTMH) is a rare sequela to submacular hemorrhage. Herein, the authors report a case of an 80-year-old man actively being treated for neovascular age-related macular degeneration who presented with sudden vision loss in the right eye. Examination with optical coherence tomography (OCT) imaging revealed submacular hemorrhage. The patient underwent vitrectomy with subretinal tissue plasminogen activator (tPA) with no intraoperative complications. Dilated fundus examination and OCT imaging revealed a FTMH at postop week 1. Possible causes for MH development include the submacular hemorrhage itself and subretinal administration of the tPA infusion. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:e257–e259.]

The authors describe a case of para-central acute middle maculopathy (PAMM) in a 75-year-old man who had recently undergone cardiac catheterization. Imaging with simultaneous en face optical coherence tomography (OCT) and OCT angiography (OCTA) revealed signal abnormalities localized to the deep capillary plexus. This case highlights the ability of OCTA to image and localize retinal disease by vascular distribution, previously difficult with conventional fluorescein angiography, and lends evidence to the belief that PAMM is caused by vascular injury to the intermediate and deep capillary plexus. [[ Ophthalmic Surg Lasers Imaging Retina . 2015;46:972–975.]

RNA antisense oligonucleotide therapy to restore normal splicing of a ciliopathy gene shows promising safety and efficacy results in a clinical trial to treat a form of childhood blindness.

Leber congenital amaurosis due to CEP290 ciliopathy is being explored by treatment with the antisense oligonucleotide (AON) sepofarsen. One patient who was part of a larger cohort (ClinicalTrials.gov NCT03140969 ) was studied for 15 months after a single intravitreal sepofarsen injection. Concordant measures of visual function and retinal structure reached a substantial efficacy peak near 3 months after injection. At 15 months, there was sustained efficacy, even though there was evidence of reduction from peak response. Efficacy kinetics can be explained by the balance of AON-driven new CEP290 protein synthesis and a slow natural rate of CEP290 protein degradation in human foveal cone photoreceptors. Post hoc analyses and follow-up of a patient with Leber congenital amaurosis treated with the antisense oligonucleotide sepofarsen as part of a clinical trial indicates sustained improvement of vision 15 months after receiving a single dose of the drug.