Retinopuncture: A Low-invasive Technique in the Treatment of Macular Subretinal Hemorrhages
In recent years, retinal surgeons have shown keen interest in minimally invasive methods of treating macular subretinal hemorrhages. At the URETINA 2017 Congress, Dr. L. N. Boriskina and from Volgograd, Russia, and colleagues shared their experience in this emerging field in a paper entitled “Results of retinopuncture in treatment of macular subretinal hemorrhages.” The team followed-up with nine patients presenting with macular subretinal hemorrhages of different etiologies, such as posterior contusion syndrome with ruptured choroid (3 cases), idiopathic macular hemorrhage (3 cases), age related macular degeneration (2 cases) and hypertensive disease (1 case). The team performed retinopuncture using the Nd:YAG laser LPQ 3106 Super Q Lazerex (Ellex, Adelaide, Australia), at a wavelength of 1064 nm, focusing epithelium detachment. The resulting hemopthalmos in these patients responded to treatment by medication. This technique resulted in reliable improvements in visual acuity of up to 0.54± 0.1. Dr. Boriskina concluded that “retinopuncture performed in the early onset period is a highly effective, low invasive method of treatment of subretinal hemorrhages of various causations, and provides a significant improvement in visual function.”
OCTA, A Useful Tool in the Assessment of PCV Patients
Currently, there is limited data on the use of OCT angiography in assessing patients with polypoidal choroidal vascular (PCV) lesions. Therefore, Dr. Eung Suk Kim from the Department of Ophthalmology, Kyung Hee University Hospital, Seoul, Korea, and colleagues conducted a retrospective study aimed at elucidating the OCTA findings before and after treatment of patients with PCV. These patients received either monotherapy with intravitreal anti-VEGF or in combination with photodynamic therapy. This was a retrospective study which included data from 16 eyes diagnosed with treatment-naïve PCV using indocyanine green angiography (ICGA). In this study, Dr. Kim observed that the branching vascular networks (BVNs) showed more clearly on the OCTA, when compared to the ICGA, while polyps were better visualized using the ICGA. However, the OCTA remains an important, non-invasive tool for detecting vascular changes in PCV. Presenting findings at the recently held EURETINA 2017 Congress in Barcelona, Spain, Dr. Kim concluded that “OCTA patterns of the polypoidal lesions and the BVN are helpful in understanding the pathology of polypoidal choroidal vasculopathy and therapeutic outcomes.”
3D Bioprinting: Let’s Print Some Retinal Cells!
3D bioprinting technology can be used to generate in-vitro 3D tissue models for biomedical applications with great accuracy and efficiency. These tissue models mimic cell arrangements in native tissue and organs, allowing increased flexibility in experimental mechanistic evaluation of diseases as well as evaluation of possible therapeutic targets of new drugs. At the EURETINA 2017 Congress, Dr. Augustinus Laude from Singapore, presented data of a study which explored the use of 3D bioprinting to precisely deliver cells and biomolecules at fixed point levels as a precursor to micro-tissues, microorganisms and extracellular models for potential applications in retinal diseases. The research team set out to bioprint a 3D retinal tissue model, composed of human retinal pigmented epithelial cell line (ARPE- 19) and human retinoblastoma cell line (Y79 cells). Both these cells lines could be bioprinted to discrete places with precision to stimulate key aspects of native disease tissue components with verified quality. The bioprinting process did not involve any scaffolding materials, yet the printed cells managed to survive to 14 days and develop some cellular features with tissue-like distribution and density. Based on these findings, Dr. Laude concluded that “bioprinting technology can be used to generate retinal bilayer constructs which show excellent cell viability and functionality up to 14 days of co-culture.” However, more work will be needed on longer-term survival and cell differentiation potential of these 3D bioprinted cells.
Long-term Efficacy and Safety of Photodynamic Therapy on Central Serous Chorioretinopathy
Dr. Young Joo Park, Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea, and colleagues investigated the long-term efficacy and safety of photodynamic therapy on central serous chorioretinopathy (CSC). To do this, they conducted a retrospective case series, which included patients treated with verteporfin photodynamic therapy (PDT) at the Seoul National University between March 2005 and March 2017. The measured BCVA and central foveal thickness at baseline and assessed response rates, recurrence and complications. In total, the team studied 77 eyes of 74 patients (32% female) over a mean period of 57 months. Mean baseline refractive error was -0.46±1.50. Nine percent of the patients were hypertensive, and 13% had received previous CSC treatment. Total PDT count per person was 1.2 ± 0.4. Following PDT, recurrence rate was 18%, and retreatment using additional PDT resulted in excellent response rates of 83.3%. During the recent EURETINA 2017 Congress, Dr. Park reported that “verteporfin PDT for treatment of CSC showed good efficacy and visual anatomical outcomes, as well as good safety profiles in the long term follow-up.”
Analysis of Cases that Develop Rhegmatogenous Retinal Detachment after Secondary Cataract YAG Capsulotomy
At the recent EURETINA 2017Congress in Barcelona, Spain, Dr. N. Pomytkina from Russia, presented a paper from her research group which analyzed cases of development of rhegmatogenous retinal detachment in patients after secondary cataract YAG capsulotomy. For this, they conducted a retrospective analysis of patients’ records from 2013 to 2016. Nineteen cases of retinal detachment were identified (26% female) with a mean age of 63 years. Dr. Pomytkina reported that YAG capsulotomy of secondary cataract is a risk factor for retinal detachment. In addition, in the immediate period following YAG capsulotomy, the development of retinal detachment is caused by formation of valvular ruptures. Therefore, Dr Pomytkina emphasized that thorough examination of the retinal periphery and implementation of limiting laser coagulation of the retina plays a pivotal role in the prevention of retinal detachment after secondary YAG associated capsulotomy.
25-Gauge Suture- less Scleral Fixation of Posterior Chamber Intraocular Lens Implant
Intraocular lenses (IOLs) provide better vision in patients who have had cataract extraction or dislocated lens. However, posterior chamber IOL implantation remains difficult, especially in the absence of capsular support. At the recent EURETINA 2017 Congress, Dr. Muhammed Amer Awan from Shifa International Hospital, Islamabad, Pakistan, and colleagues set out to study the outcome and safety of the 25-G suture-less scleral fixation of posterior chamber IOL. This was a retrospective, single hospital-based interventional case series that included eyes with inadequate or no capsular support. In these cases, patients received a 25-G, 3 ports pars plana vitrectomy. All eyes (14) had improvements in vision. There was no significant pre- or postoperative complication reported. Based on findings, Dr. Awan concluded that the 25-G suture-less, sclera fixation of PCIOL is an excellent technique to achieve better visual outcomes on eyes with inadequate or absent capsular support.
Key Takeaways from the Aflibercept Symposium at EURETINA 2017
Takeaway #1: Aflibercept and the Role of a Multi-Target Approach to Retinal Disease
Based on a presentation by Prof. Francine Behar-Cohen, Professor of Ophthalmology and Vitreoretinal Surgeon, Assistance Publique – Hôpitaux de Paris, France
Aflibercept (Eylea, Bayer, Leverkusen, Germany) is the only approved intravitreal anti-VEGF (vascular endothelial growth factor) targeting different VEGF receptor ligands: VEGF-A, VEGF-B, placental growth factor (PLGF) and galectin-1, with greater affinity than the natural receptor. Furthermore, the aflibercept molecule has been optimized to have a high binding affinity for VEGF-A; 100 times more potent than ranibizumab (Lucentis, Novartis, Basel, Switzerland). This results in a prolonged intraocular VEGF-A suppression with a half-life of about 9 days.
In a study of 7 patients who interrupted use of aflibercept and ranibizumab, and subsequently had quantification of intraocular aflibercept levels, the duration of suppression of VEGF-A was found significantly longer, as compared to ranibizumab. To summarize VIEW 1 and VIEW 2 study data, notable findings demonstrate that giving monthly or bimonthly injections result in similar visual gains, and that administering multiple anti-VEGF injections has become an issue for many patients. In one study presented, patients with central retinal vein occulsion (CRVO) who were receiving multiple anti-VEGF injections were switched to aflibercept. This resulted in an extended duration of intervals between injections, with a gain of 0.5 lines after 6 months, and a gain of 3 lines after one year. Switching patients to aflibercept allows for extended interval between injections, which would mean less frequency of injections for patients.
Another important message is the binding of aflibercept to galectin-1. Galectin-1 has been shown to potently stimulate endothelial cells and induce neovascularization by binding to VEGFR-2 and preventing endocytosis of the receptor, potentiating cellular activation and inflammation. This has been shown in mice deficient in galectin-1, which develop less neovascularization, and a reduced area of hypoxia in a model of retinopathy of prematurity (ROP) as compared to wild type. Aflibercept efficiently inhibits galectin-1 mediated activation of VEGFR-2.
Takeaway #2: Innovative Imaging with Aflibercept
Based on a presentation by Prof. Giovanni Staurenghi, Professor of Ophthalmology, Chair of the University Eye Clinic, Director of the University Eye Clinic Department, Luigi Sacco Hospital, Milan, Italy
An important question in clinical trials evaluating efficacy of new retinal drugs is: What is the retinal thickness we need to measure and how do we measure this? Also, how much can we relate that to visual acuity (VA)? It is important is to be able to demonstrate that thickness is related to VA as this is a critical measure of reduced inflammation. In optical coherence tomography angiography (OCTA) imaging, the main advantage is that for the first time we can study images of different depths. This is of key importance in patients with diabetic retinopathy where there is a need for depth analysis to identify microaneurysms. An important technique today is ultra-widefield imaging, which becomes a key technology for studying peripheral lesions associated with perfusion. And it has been used to demonstrate the ability of aflibercept to reduce the unperfused areas of the retina. Imaging also has been used to evaluate retinal function and there are series of possibilities with microperimetry and contrast sensitivity. These techniques evaluate the function of the eye and are important parts of clinical trials where geographic atrophy and microperimetry are critical end points. However, functional tests are difficult to perform in routine clinical care. New emerging technologies, particularly OCTs, will allow better understanding of results of clinical trials.
Takeaway #3: Emerging Clinical Evidence with Aflibercept
Based on a presentation by Assoc. Prof. Gemmy Cheung, Senior Consultant Ophthalmologist at Singapore National Eye Centre (SNEC) and Clinician Investigator at the Singapore Eye Research Institute (SERI), Singapore
New clinical trials have allowed us to learn more about extensions and modifications in clinical indications for aflibercept. A wealth of data has already demonstrated that aflibercept monotherapy is effective in improvement of vision and regression of polyps in patients with polypoidal choroidal vasculopathy (PCV), a disease characterized by abnormal choroidal vascular lesions which end in polypoidal dilatations.
The PLANET study, a randomized, double blind, placebo controlled multi-center phase 3 study evaluated the effect of aflibercept on PCV with or without rescue photodynamic therapy (PDT). The study showed that aflibercept resulted in anatomical improvement in over 80% of patients and 40% had achieved complete regression of polyps. Importantly, aflibercept monotherapy led to significant gains in visual acuity in patients with PCV.
The ALTAIR study, a phase 4 trial designed to demonstrate efficacy of aflibercept in a treat-and-extend protocol, showed VA gains of 8 to 9 letters from baseline to week 52. It also demonstrated that up to 50% of patients achieved a treatment interval of 12 weeks or more, with no safety signals.
The CLARITY study was designed to study the efficacy and safety of aflibercept in the treatment of proliferative diabetic retinopathy (PDR). At the end of the study, aflibercept therapy resulted in significantly superior disease regression and improved vision in patients with PDR as compared to standard of care.
Editor’s Note: The 17th Congress of the European Society of Retina Specialists (EURETINA 2017) was held in Barcelona, Spain, on September 7 to 10, 2017.
