Ranibizumab in retinal vein occlusion: Treatment recommendations by an expert panel

Retinal vein occlusion (RVO) is a common cause of retinal vascular disease, resulting in potentially irreversible loss of vision despite the existence of several therapeutic options. The humanised monoclonal antibody fragment ranibizumab binds to and inhibits vascular endothelial growth factor, a key driver of macular oedema in RVO. In 2010, ranibizumab was approved in the USA for the treatment of macular oedema in RVO and, in 2011, ranibizumab was approved in the European Union for the treatment of visual impairment caused by macular oedema secondary to RVO in branch and central RVO. Ranibizumab provides an additional therapeutic option for this complex disease: an option that was not fully considered during the preparation of current international guidelines. An expert panel was convened to critically evaluate the evidence for treatment with ranibizumab in patients with visual impairment caused by macular oedema secondary to RVO and to develop treatment recommendations, with the aim of assisting physicians to optimise patient treatment

Sustained Benefits of Ranibizumab with or without Laser in Branch Retinal Vein Occlusion: 24-Month Results of the BRIGHTER Study

Purpose To evaluate the long-term (24-month) efficacy and safety of ranibizumab 0.5 mg administered pro re nata (PRN) with or without laser using an individualized visual acuity (VA) stabilization criteria in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). Design Phase IIIb, open-label, randomized, active-controlled, 3-arm, multicenter study. Participants A total of 455 patients. Methods Patients were randomized (2:2:1) to ranibizumab 0.5 mg (n = 183), ranibizumab 0.5 mg with laser (n = 180), or laser (with optional ranibizumab 0.5 mg after month 6; n = 92). After initial 3 monthly injections, patients in the ranibizumab with or without laser arms received VA stabilization criteria-driven PRN treatment. Patients assigned to the laser arm received laser at the investigator's discretion. Main Outcome Measures Mean (and mean average) change in best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) from baseline to month 24, and safety over 24 months. Results A total of 380 patients (83.5%) completed the study. Ranibizumab with or without laser led to superior BCVA outcomes versus laser (monotherapy and combined with ranibizumab from month 6; 17.3/15.5 vs. 11.6 letters; P P P = 0.4259). A greater reduction in CSFT was seen with ranibizumab with or without laser versus laser monotherapy over 24 months from baseline (ranibizumab monotherapy −224.7 μm, ranibizumab with laser −248.9 μm, laser [monotherapy and combined with ranibizumab from month 6] −197.5 μm). Presence of macular ischemia did not affect BCVA outcome or treatment frequency. There were no reports of neovascular glaucoma or iris neovascularization. No new safety signals were identified. Conclusions The BRIGHTER study results confirmed the long-term efficacy and safety profile of PRN dosing driven by individualized VA stabilization criteria using ranibizumab 0.5 mg in patients with BRVO. Addition of laser did not lead to better functional outcomes or lower treatment need. The safety results were consistent with the well-established safety profile of ranibizumab

Individualized Stabilization Criteria-Driven Ranibizumab versus Laser in Branch Retinal Vein Occlusion

Purpose To compare the 6-month efficacy and safety profile of an individualized stabilization criteria-driven pro re nata (PRN) regimen of ranibizumab 0.5 mg with or without laser versus laser alone in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). Design A 24-month, prospective, open-label, randomized, active-controlled, multicenter, phase IIIb study. Participants A total of 455 patients. Methods Eligible patients were randomized 2:2:1 to receive ranibizumab (n = 183), ranibizumab with laser (n = 180), or laser only (n = 92). Patients treated with ranibizumab with or without laser received a minimum of 3 initial monthly ranibizumab injections until visual acuity (VA) stabilization, and VA-based PRN dosing thereafter. In the ranibizumab with laser and laser-only groups, laser was given at the investigator's discretion at a minimum interval of 4 months and if VA was <79 letters. Main Outcome Measures Mean change from baseline at month 6 in best-corrected visual acuity (BCVA) (primary end point) and central subfield thickness, and safety over 6 months. Exploratory objectives were to evaluate the influence of baseline BCVA, disease duration, and ischemia on BCVA outcomes at month 6. Results Baseline mean BCVA was 57.7 letters, and mean BRVO duration was 9.9 months. Ranibizumab with or without laser was superior to laser only in improving mean BCVA from baseline at month 6 (14.8 and 14.8 vs. 6.0 letters; both P < 0.0001; primary end point met). Patients with a shorter BRVO duration at baseline had a higher mean BCVA gain than those with a longer BRVO duration. Patients with a poor baseline VA had a better BCVA gain than those with a higher baseline VA, although final BCVA was lower in those with poor baseline VA. In the ranibizumab with or without laser groups, the presence of some macular ischemia at baseline did not influence mean BCVA gains. There were no new ocular or nonocular safety events. Conclusions Ranibizumab with an individualized VA-based regimen, with or without laser, showed statistically significant superior improvement in BCVA compared with laser alone in patients with BRVO. Overall, there were no new safety events other than those reported in previous studies

Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion: Twelve-Month Results of the CRYSTAL Study

Purpose To assess the 12-month efficacy and safety profile of an individualized regimen of ranibizumab 0.5 mg driven by stabilization criteria in patients with macular edema secondary to central retinal vein occlusion (CRVO). Design A 24-month, prospective, open-label, single-arm, multicenter study. Participants Three hundred fifty-seven patients. Methods Patients were treated with monthly ranibizumab 0.5-mg injections (minimum of 3 injections) until stable visual acuity (VA) was maintained for 3 consecutive months. Thereafter, ranibizumab 0.5 mg was dosed as needed if monthly monitoring indicated a loss of VA resulting from disease activity. Main Outcome Measures Mean change from baseline at month 12 in best-corrected VA (BCVA; primary end point) and safety over 12 months. The efficacy of this regimen in subgroups categorized by baseline BCVA score, CRVO duration, or presence of macular ischemia (exploratory analysis). Results At baseline, the mean BCVA was 53.0 letters and mean CRVO duration was 8.9 months (median, 2.4 months). Ranibizumab 0.5-mg treatment resulted in a statistically significant mean gain in BCVA from baseline at month 12 of 12.3 letters (standard deviation [SD], 16.72 letters; P < 0.0001). The mean number of ranibizumab injections up to month 12 was 8.1 (SD, 2.77). At month 12, mean BCVA gains were similar with or without macular ischemia at baseline (11.6 vs. 12.1 letters); the mean BCVA gain was higher with baseline CRVO duration of less than 3 months (13.4 letters) than with a longer duration (≥3-<9 months, 11.1 letters; ≥9 months, 10.9 letters). Patients with lower baseline BCVA had larger mean BCVA gains at month 12 than those with higher baseline BCVA (≤39/40-59/≥60 and 18.0/12.7/8.9 letters, respectively), although the absolute BCVA at month 12 was higher with higher baseline BCVA. No new ocular or nonocular safety events were observed. Conclusions An individualized dosing regimen of ranibizumab 0.5 mg driven by stabilization criteria for up to 12 months resulted in significant BCVA gain in a broad population of patients with macular edema secondary to CRVO, including those with macular ischemia at baseline. The safety findings were consistent with those reported in previous ranibizumab studies in patients with CRVO

Safety and Feasibility of a Novel Sparse Optical Coherence Tomography Device for Patient-Delivered Retina Home Monitoring

Purpose To study a novel and fast optical coherence tomography (OCT) device for home-based monitoring in age-related macular degeneration (AMD) in a small sample yielding sparse OCT (spOCT) data and to compare the device to a commercially available reference device. Methods In this prospective study, both eyes of 31 participants with AMD were included. The subjects underwent scanning with an OCT prototype and a spectral-domain OCT to compare the accuracy of the central retinal thickness (CRT) measurements. Results Sixty-two eyes in 31 participants (21 females and 10 males) were included. The mean age was 79.6 years (age range, 69-92 years). The mean difference in the CRT measurements between the devices was 4.52 μm (SD ± 20.0 μm; range, -65.6 to 41.5 μm). The inter- and intrarater reliability coefficients of the OCT prototype were both >0.95. The laser power delivered was <0.54 mW for spOCT and <1.4 mW for SDOCT. No adverse events were reported, and the visual acuity before and after the measurements was stable. Conclusion This study demonstrated the safety and feasibility of this home-based OCT monitoring under real-life conditions, and it provided evidence for the potential clinical benefit of the device. Translational Relevance The newly developed spOCT is a valid and readily available retina scanner. It could be applied as a portable self-measuring OCT system. Its use may facilitate the sustainable monitoring of chronic retinal diseases by providing easily accessible and continuous retinal monitoring

Enucleation and development of cluster headache: a retrospective study

BACKGROUND: Cluster headache (CH) is a neurovascular, primary headache disorder. There are, however, several case reports about patients whose CH started shortly after a structural brain disease or trauma. Motivated by a patient who developed CH 3 weeks after the removal of an eye and by similar case reports, we tested the hypothesis that the removal of an eye is a risk factor for CH. METHODS: A detailed headache questionnaire was filled out by 112 patients on average 8 years after enucleation or evisceration of an eye. RESULTS: While 21 % of these patients experienced previously unknown headaches after the removal of an eye, no patient fulfilled the diagnostic criteria for CH. CONCLUSION: Our data does not suggest that the removal of an eye is a major risk factor for the development of CH

The Use of Optical Coherence Tomography for the Detection of Early Diabetic Retinopathy

Diabetic retinopathy (DR) is one of the leading causes of vision loss globally with a severe burden on all societies due to its high treatment and rehabilitation costs. The early diagnosis of DR may provide preventive steps (including retinal laser therapy and tight carbohydrate, blood pressure, and cholesterol control) that could in turn help to avoid progression of the pathology with the resultant vision loss. Optical coherence tomography (OCT) enables the in vivo structural imaging of the retina, providing both qualitative (structure) and quantitative (thickness) information. In the past decades, extensive OCT research has been done in the field of DR. In the present review, we are focusing on those that were aiming at detection of the earliest retinal changes before DR could be diagnosed funduscopically. The latest, widely available technology of spectral-domain (SD-)OCT comes with a fast and reliable retinal imaging, which, together with the most recent developments in image processing and artificial intelligence, holds the promise of developing a quick and efficient, state-of-the-art screening tool for DR

Immunhistochemische Befunde retrokornealer Membranen von Augen mit kornealer Dekompensation nach komplizierten intraokularen Eingriffen

BACKGROUND Retrocorneal membranes (RCMs) may result from epithelial ingrowth, stromal keratocytic downgrowth, fibrous metaplasia of the corneal endothelium, or a combination of these processes. In an institutional case series, the clinical history, ocular findings, and immunohistochemical staining results of RCMs were analysed in patients with unilateral corneal decompensation after complicated intraocular surgery. METHODS AND PATIENTS Between January 2021 and September 2022, six retrocorneal membranes were excised during Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) procedures and classified after screening with haematoxylin and eosin, periodic acid-Schiff, elastic van Gieson staining, and immunohistochemical screening with cytokeratin 7 (CK7), anti-cytokeratin (CAM5.2 and AE1/3), cell surface glycoprotein CD34, smooth muscle actin (α-SMA), and vimentin. RESULTS On the basis of the immunohistochemical screening, the majority of excised RCMs (5 of 6) could histopathologically be classified as membranes originating from fibrous metaplasia of the corneal endothelium. All these RCMs were positive for CK7, α-SMA, and vimentin and negative for CAM5.2 and CD34. In one patient, an RCM had developed after 18 days of corneal contact to a free-floating dexamethasone implant in the anterior chamber and was classified as originating from stromal keratocyte downgrowth (α-SMA- and vimentin-positive, all others negative). All eyes in this series had a previous history of complicated cataract surgery, partially with subsequent intraocular lens exchange. No eyes after previous penetrating keratoplasty were in this series. CONCLUSIONS In this series of eyes with previous complicated intraocular interventions (in most cases cataract surgery and revisions), the dominating RCM belonged to the type originating from fibrous metaplasia of the corneal endothelium

Enucleation and development of cluster headache: a retrospective study

Abstract Background Cluster headache (CH) is a neurovascular, primary headache disorder. There are, however, several case reports about patients whose CH started shortly after a structural brain disease or trauma. Motivated by a patient who developed CH 3 weeks after the removal of an eye and by similar case reports, we tested the hypothesis that the removal of an eye is a risk factor for CH. Methods A detailed headache questionnaire was filled out by 112 patients on average 8 years after enucleation or evisceration of an eye. Results While 21 % of these patients experienced previously unknown headaches after the removal of an eye, no patient fulfilled the diagnostic criteria for CH. Conclusion Our data does not suggest that the removal of an eye is a major risk factor for the development of CH.</p

Ranibizumab in retinal vein occlusion: treatment recommendations by an expert panel

Retinal vein occlusion (RVO) is a common cause of retinal vascular disease, resulting in potentially irreversible loss of vision despite the existence of several therapeutic options. The humanised monoclonal antibody fragment ranibizumab binds to and inhibits vascular endothelial growth factor, a key driver of macular oedema in RVO. In 2010, ranibizumab was approved in the USA for the treatment of macular oedema in RVO and, in 2011, ranibizumab was approved in the European Union for the treatment of visual impairment caused by macular oedema secondary to RVO in branch and central RVO. Ranibizumab provides an additional therapeutic option for this complex disease: an option that was not fully considered during the preparation of current international guidelines. An expert panel was convened to critically evaluate the evidence for treatment with ranibizumab in patients with visual impairment caused by macular oedema secondary to RVO and to develop treatment recommendations, with the aim of assisting physicians to optimise patient treatment