A 3D Approach to Vitreoretinal Surgery
In recent years, the ophthalmic world has witnessed remarkable enhancements in the surgical management of vitreoretinal diseases, mainly because of the development and availability of digital imaging systems, such as the Digitally Assisted Vitreoretinal Surgery (DAVS) 3D system (Alcon, Fort Worth, TX, USA). Digital imaging systems provide enhanced visualization, and permit adjustments in image light intensity and depth of field, making it possible to operate in very low light conditions. Furthermore, a wide variety of settings allow the surgeon to customize lighting conditions and image filters for each procedure, which is an added value in routine clinical practice.
At the recently held American Society of Retina Specialists Annual Meeting (ASRS 2017) in Boston, USA, Dr. Marco Mura, M.D., Associate Professor of Ophthalmology at the Wilmer Eye Institute, Johns Hopkins University School of Medicine in Baltimore, Maryland, USA and Chief of the Retina Division at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, shared recent insights into the role of digital 3D imaging in the surgical management of vitreoretinal disease.
In an effort to provide supportive data on quantifiable parameters associated with the performance and use of the 3D DAVS viewing system by ophthalmologists in routine clinical practice, Dr. Mura and colleagues performed a subjective, prospective evaluation, utilizing a set of questionnaires administered to surgeons across different levels of training (two consultants and five fellows). The study was conducted in standard surgical settings in two teaching hospitals and compared standard PPV 23-, 25- and 27-G with digital channels. Cameras used in the study were the Leica M844 and M822 at 175-200 mm focal lengths and an aperture of approximately 35%. Intra-ocular illumination was tangential and direct, with brightness, hue and gain adjusted with color channels (i.e. vitreous removal, diabetic, and macula filters).
Study participants were asked if the procedure was easier, same, worse, much worse or better with the surgical filters. The study team included 398 patients over the 3.5-year follow-up period, and these patients were homogenously distributed among the fellows and consultants. A majority of the surgeons (60%) found the procedure better or much better than standard settings (without filters). Furthermore, with the diabetic filters, 70% of surgeons found the procedure either better or much better. When asked about the depth of field filters compared to standard optical microscopes, 100% preferred the depth of field filters. Based on their findings, Dr. Mura and colleagues concluded that, “the 3D DAVS enhances surgical maneuvers and makes them easier to perform through increased depth of field. The possible use of these color channels offers superior ergonomics and a better teaching environment.”
Aflibercept Treatment PERMEATEs Better in DME and RVO
At the recent ASRS 2017 meeting in Boston, Dr. Justin Ehlers, M.D. from Cleveland, Ohio, USA, presented data from the PERMEATE (Peripheral and Macular Retinal Vascular Perfusion and Leakage in DME and RVO) study, which was designed to characterize longitudinal retinal vascular dynamics with an angiographic quantitative assessment tool for both diabetic retinopathy and retinal vein occlusion.
The study included male and female patients ≥ 18 years of age, with foveal-involving retinal edema secondary to DME or RVO, and E-ETDRS best-corrected visual acuity of 20/25 or worse in the study eye. Patients with any prior or concomitant therapy to treat DME or RVO in the study eye, prior laser treatment for retinal disease, prior vitrectomy, trabeculectomy, other filtration surgery or history of retinal detachment in study eye were excluded. Patients with significant vitreous hemorrhage obscuring view of macula or retinal periphery and patients unable to undergo fluorescein angiography were also excluded.
All patients received initial monthly treatment of aflibercept (Eylea, Bayer, Leverkusen, Germany), quarterly ultra-wide field fluorescein angiography (UWFA) and optical coherence tomography angiography (OCTA).
Dr. Ehlers presented the 6-month interim data analysis for the 26 patients who had completed their month 6 visits. The mean age of subjects was 67 years, and majority (62%) were men. There was an even patient distribution between diabetic macular edema and retinal vein occlusion. The baseline mean visual acuity was 20/80 and baseline mean central subfield thickness was 505 µm. Dr. Ehlers highlighted that excellent outcomes of visual acuity were seen at 6 months, with mean score of 20/40, and 38% of eyes gaining 3 lines.
From an anatomic standpoint, he noted significant improvements at month 6, with mean CST of 265 µm, 54% of eyes achieving dryness via OCT, and 100% of eyes with no sub-retinal fluid. When they assessed qualitative data, they found significant reductions in leakage, micro-aneurysms, macular and peripheral ischemia at month 6, when compared to baseline.
Quantitative leakage assessment revealed an overall 47% reduction at month 6 compared to baseline, especially marked at the posterior pole (83%) and mid-peripheral area (87%). The leakage index at month 6 was 1%. Furthermore, analysis of the evolution of micro aneurysms revealed an overall 10% reduction when compared to baseline, which was notable at the posterior pole (54%). The ischemia index, assessed at month 6, showed an overall 53% reduction when compared to baseline. Based on their findings from this treatment naive cohort study, Dr. Ehlers and colleagues concluded that aflibercept therapy resulted in significant improvements in visual acuity and reduction in macular edema. Furthermore, he proposed that “quantitative segmentation of ultra wide field angiography may provide unique opportunities for understanding of important underlying changes in retinal vascular dynamics, such as leakage, micro-aneurysms and ischemia.”
Can preoperative anti-VEGF administration reduce postoperative vitreous hemorrhage and cystoid macular edema?
Pars plana vitrectomy (PPV) is the treatment of choice for non- resolving vitreous hemorrhage (VH), and preoperative anti-VEGF is effective in reducing intraoperative bleeding by reducing neovascularization, but is washed out during vitrectomy.
Postoperative vitreous hemorrhage (POVH) is one of the most common adverse events following vitrectomy for non-resolving VH. The incidence of postoperative cystoid macular edema remains poorly documented, and possible associated factors include diabetic macular edema or postoperative inflammation following surgery or peripheral panretinal photocoagulation (PRP) endolaser.
In order to elucidate the role of preoperative anti-VEGF administered intraoperatively during vitrectomy for vitreous hemorrhage, Dr. Manish Nagpal MBBS, MS (Ophthalmology), FRCS(Edinburgh, UK) from the Retina Foundation & Eye Research Centre (Ahmedabad, India) and colleagues reviewed data from 312 eyes from 224 patients with non-resolving vitreous hemorrhage, and their findings were presented at the recent ASRS 2017 meeting in Boston, USA. In this retrospective comparative study, the patients were divided into two groups: group A (165 patients who did not receive anti-VEGF; [control]) and group B (147 patients, who received anti-VEGF). Patients were followed up on 1st, 30th, 90th and 180th postoperative day. Postoperative vitreous hemorrhage was defined as vitreous hemorrhage occurring between 1 and 6 months from the date of surgery. Patients included in the study needed to have non-resolving vitreous hemorrhage, no traction on USG, no prior anti-VEGF received in the last 3 months and no prior eye surgery.
Postoperatively, the incidence of POVH was significantly lower in group B, which received anti-VEGF (9.5%) when compared to group A, which did not receive anti-VEGF (21.8%) (p=0.01). Furthermore, Dr. Nagpal and colleagues found reduced incidence of vasculitis and venous occlusion in patients who received anti-VEGF. When stratification based on prior laser treatment was done, group A patients still had a higher incidence of POVH. Furthermore, when the study team measured central foveal thickness (CVT) they found lower CVT measurements in group B patients, who were treated with anti-VEGF. Dr. Nagpal and colleagues concluded that “preoperative anti-VEGF treatment reduces the incidence of POVH and more likely to reduce cystoid macular edema.”
Stem Cell Therapy for Ophthalmic Disorders: The Good, the Bad and the Ugly
At the ASRS 2017 meeting in Boston, USA, Dr. Mark Humayun, M.D., of the USC Roski Eye Institute (Los Angeles, California, USA) led a panel discussion on stem cell therapy and its potential application in treating ophthalmic disorders.
In his introduction, Dr. Humayun stated that the commercialization of unproven stem cell therapies has become popular in recent years. The unproven stem cell therapy industry is estimated at up to $2.4 billion, and involves over 60,000 patients per year, who pay out-of-pocket up to $40,000 per treatment. In terms of the regulatory approach to stem cell therapy, there is a tiered, risk-based framework for human cells or tissues that are intended for implantation, infusion or transfer. The biggest success has been in orthopedic diseases.
There are strict regulations under the Public Health Service (PHS) Act for highly processed or manipulated tissues, used for other than their normal function, combined with non-tissue components or used for metabolic purposes. Demonstration of clinical safety and effectiveness is mandatory and these require pre-market review.
Conventional tissue grafts undergo little processing. For example, skin grafts, and when used for their normal function are identified as lower risk, and regulated by section 361 of the PHS Act, which specifies guidelines on prevention of communicable diseases. For conventional tissue grafts, pre-market review and approval are not required.
Dr. Humayun discussed stromal vascular fraction of adipose tissue (SVF), which is a rich source of pre-adipocytes, mesenchymal cells, endothelial cells, progenitor cells, B cells, T cells and adipose tissue macrophages. Collecting the SVF is very simple and can be performed in less than 60 minutes. It involves minimal manipulation of adipose tissue, and the cells obtained can be injected quickly back into the same patient.
Three cases of vision loss after intravitreal stem cell injection were presented and discussed by the panelists. All patients underwent intravitreal injection of 0.1cc autologous adipose tissue-derived stem cells. The average cost of the procedure was $5,000. Patients signed consent forms for the procedure, but no study consent, even though they were aware of study listing on ClinicalTrials.gov, a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. Potential causes of vision loss in these patients include contamination of cells with toxic substances, use of trypsin or collagenase during stem cell isolation and effect of growth factors and cytokines in the vitreous and blood, driving undifferentiated stem cells to mesenchymal cells.
According to the panelists, stem cell treatment for ophthalmic disorders has great potential. However, the methods utilized in isolation of these cells and the delivery methods need to be scrutinized to minimize risks to patients enrolling in clinical trials.
Furthermore, patients and physicians must be aware of potentially devastating outcomes of intravitreal stem cell therapy provided by private, non-FDA approved facilities which are not affiliated with medical centers, even if these studies are IRB approved and/or listed on clinicaltrials.gov.
A Revolution in the Management of Advanced Maculopathies
At the recently held ASRS 2017 meeting in Boston, USA, researchers from Italy reported that the IOL-VIP (intraocular lens for visually impaired people) revolution system is safe, well-tolerated, and effective in improving best-corrected visual acuity (BCVA) in patients with low vision due to advanced maculopathies.
In a paper entitled Intraocular Telescopic System IOL-VIP for Advanced Maculopathies, Dr. Fabio Patelli, M.D., shared findings of a retrospective, multicenter evaluation of the IOL-VIP system. Patients were diagnosed with AMD or other macular diseases, with BCVA >0.3 and with preserved visual field at baseline. Postoperative VA and safety data were collected after two years of follow-up. Out of the 82 eyes from 64 patients, preoperative BCVA was <0.1 in 58 eyes; 56 (96.5%) of these eyes achieved postoperative BCVA of >0.1, and these patients now use optical magnifiers.
As noted by Dr. Patelli, the IOL-VIP system has several advantages. Firstly, the eye movement can be controlled with the field of view and its 1.3X magnification allows a stable increase of visual acuity, both for distance and for near vision. In addition, its prismatic effect facilitates deviation of images into the preferred retinal locus. It is also available as a binocular implant.
The research team concluded that the IOP-VIP Revolution system is safe and well-tolerated. Surgery is not difficult, and BCVA results are equal to, or better than, predicted BCVA simulation tests. Furthermore, visual field reduction is minimal (between 7-10%) and comfortable for patients, and the binocular implant is well-tolerated. Finally, in most cases, patients can use an optical magnifier instead of electronic CCTV.
Editor’s Note: The American Society of Retina Specialists (ASRS) 2017 Annual Meeting was held in Boston, Massachusetts, on August 11 to 15, 2017. Reporting for this story also took place at ASRS 2017.
