The 34th Annual Meeting of the American Society of Retina Specialists (ASRS) was held from 9–14 August, 2016 in San Francisco, California. A contingent of around 10 Australian and New Zealand ophthalmologists joined hundreds of delegates from around the world to attend this meeting, one of the largest of its kind in retinal-related diseases.
Optical coherence tomography angiography (OCT-A) is changing the landscape of medical retina and our understanding of pathophysiology. This technique uses principles of the doppler effect to detect flow within retinal vessels. Unlike conventional fluorescein angiography, it can be performed without the use of a dye contrast and on the same machine which performs conventional OCT. It therefore has the advantages of avoiding potential complications of fluorescein dye (including rare events of anaphylaxis) combined with a faster acquisition time. In addition, several retinal vessels can be seen using OCT-A that cannot be visualised with conventional fluorescein angiography. These include the radial peripapillary capillaries and the deep capillary plexus. The main disadvantages at the moment are the numerous artefacts that occur with image acquisition, including projection artefact and motion (white line) artefact. OCT-A does not detect leakage from vessels, but is useful in detecting flow. Considerable debate remains surrounding the interpretation of images, as well as how best to manage findings. For instance, with this technique choroidal new vessels can be detected that are fluorescein angiographically ‘silent’. These vessels are seen on OCT-A but not fluorescein angiography, and do not exhibit haemorrhage, fluid or lipid on clinical examination or OCT. Currently there is no consensus as to how to treat these subclinical neovascular complexes. Phil Rosenfeld MD, PhD, demonstrated the use of the outer-retinal layer and choriocapillaris (ORCC) segments on swept source OCT-A to identify such new vessels in drusen and shallow pigment epithelial detachments. This correlates with previously published histological data and indocyanine green angiography. Inspection of en face RPE maps is also suggestive of these vessels. Both he and Ching Chen MD suggest close follow-up of clinically ‘silent’ CNV without recommending treatment given the remaining uncertainty surrounding the association between anti-VEGF therapy and RPE atrophy. Richard Rosen MD, DSc(Hon) presented beautiful images of retinal vessels validating the use of OCT-A with a prototypical technique using adaptive optics confocal scanning laser ophthalmoscopy fluorescein angiography (AOSLO-FA). This new technique may form the basis of future advances in retinal imaging.
Age-related Macular Degeneration (AMD)
Genetic stratification of patients is useful in determining the role of antioxidants according to Carl Awh, MD. Using the AREDS cataract trial, researchers were able to stratify patients with high risk depending on the presence of gene mutations including CFH and ARMS2. Individuals without AMD and high genetic risk are more likely to develop intermediate AMD (40 per cent at 8.5 years), and AREDS vitamin supplements were recommended. In contrast, taking antioxidants in patients without AMD and low genetic risk was actually found to be detrimental. Genetic stratification was also found to be useful in determining response to intravitreal anti-VEGF therapy in patients with neovascular AMD. Nancy Holekamp MD presented data identifying single nucleotide polymorphisms on chromosome X that may be associated with better outcomes.
The need for ongoing treatment of neovascular AMD with intravitreal anti-VEGF therapy was highlighted by Thomas Ciulla MD, MBA. ‘Real world’ data showed worse outcomes than patients in clinical trials, with the worse prognosis in patients lost to follow up. Nizar Abdelfattah MD presented data from the TREX-AMD study. This showed no significant difference between macular atrophy rates in patients with neovascular AMD being treated with a monthly or treat and extend protocol. Previously there has been concern that intravitreal anti-VEGF therapy may be accelerating the rate of geographic atrophy. Dan Martin MD presented five-year data from the Comparison of AMD Treatments Trial (CATT), which looked at intravitreal ranibizumab, bevacizumab, monthly and PRN dosing for neovascular AMD. Between year two (the end of the initial study) and year five, there was a mean 11 letter decrease in vision, with patients ending up three letters worse than baseline. This mirrors other long-term anti-VEGF studies which show a slow gradual decline in vision after the initial two year gains. However, 50 per cent of patients still had 6/12 vision or better at five years. Despite the long-term decline, he highlighted just how much better patients were doing when compared with the pre-anti-VEGF era. By year five patients were averaging four injections per year, and 83 per cent still have persistent fluid (predominantly intraretinal). The main cause of visual decline was thought to be from atrophy of the retina and retinal pigment epithelium (geographic atrophy) as well as expansion of the CNV complex.
Digital Assisted Vitreoretinal Surgery is a new system where two cameras acquire stereoscopic images that are visualised by the surgeon wearing 3D-spectacles on a high-definition television screen
In India, a biosimilar to ranibizumab (razumab) is available to patients at a cheaper price point than the original medication, according to Alay Banker MD. Encapsulated cell therapy was shown to be inferior to intravitreal aflibercept standard of care by Szilard Kiss MD. Unfortunately, this study, attempting to produce a more durable effect with a VEGF receptor, had to be cancelled due to lack of efficacy. Engineered biopolymer thin-films have the potential to extend intravitreal drug delivery according to Robert Bhitsitkul MD, PhD. Preliminary evidence for a novel anti-VEGF and anti-angiopoietin two for the treatment of neovascular AMD and diabetic macular oedema (DMO) was discussed by Pravin Dugel MD. Jayakrishna Ambati MD discussed the potential use of nucleoside analogs and derivatives to prevent progression of dry AMD.
Retinal Vascular Occlusions
Pro re nata (PRN) treatment with intravitreal ranibizumab for macular oedema secondary to retinal vein occlusion was shown to be non-inferior to monthly treatment in the SHORE study, presented by W Clark MD. This led to fewer injections with similar visual acuity outcomes. Interestingly, Jeffrey Heier MD showed improvements in peripheral non-perfusion following intravitreal aflibercept for proliferative diabetic retinopathy and central retinal vein occlusion. These improvements appear to regress once therapy has been ceased.
A treat and extend protocol with intravitreal ranibizumab was shown to have similar efficacy to monthly treatment for DMO, as presented by John Payne MD. Previously published data from the DRCR.net Protocol T study was discussed by John Wells MD, FACS. This showed no significant difference in visual outcomes for the treatment of DMO between aflibercept, ranibizumab and bevacizumab after two years. However, for patients with worse levels of initial vision, visual acuity responses were greater for aflibercept when compared with bevacizumab, but not ranibizumab. Analogous to retinal vein occlusion, the perfusion status and diabetic retinopathy burden of patients undergoing treatment with intravitreal ranibizumab was shown to improve by Charles Wykoff MD, PhD. The implications of the DRCR.net Protocol S study was discussed by Andrew Antoszyk MD. This showed non-inferiority of intravitreal anti-VEGF compared to traditional panretinal photocoagulation for the treatment of proliferative diabetic retinopathy. Eric Chin MD discussed ocular hypertension (OHT) following intravitreal dexamethasone implantation, which is indicated in the USA for macular oedema secondary to retinal vascular occlusion, non-infectious posterior uveitis and diabetes. Peak intraocular pressure elevation occurred 1.5 0–2.5 months’ post-injection, and did not vary depending on clinical indication. Twenty-seven per cent of patients developed OHT, 21 per cent required glaucoma drops and 3 per cent underwent glaucoma surgery (all of whom had preceding glaucoma). Unlike a study presented by Jay Stewart MD, Dr. Chin did not find that multiple injections had an effect on the likelihood of OHT development.
Other Medical Retinal Conditions
Selective laser therapy (a type of subthreshold laser) was advocated by Young Jung Roh MD, for the treatment of central serous chorioretinopathy. In the medical retina case conference there was discussion of Hemorrhagic Occlusive Retinal Vasculitis (HORC), a rare but devastating complication usually following cataract surgery which related to the use of intraocular vancomycin. The hazards of unregulated treatments were highlighted by Ajay Kuriyan MD, MSc. He presented three cases of patients who went blind after undergoing intravitreal injections of autologous adipose-derived stem cells for AMD. These injections were performed at unlicensed stem cell clinics by nurses. The patients were misled to believe they were enrolling in a clinical trial, but this was not actually the case. The need for tighter regulation by the US Food and Drug Administration was discussed.
Using commercially available hardware (Heidelberg Spectralis), Netan Choudhry MD, FRCS(S) demonstrated ultra-widefield SD-OCT imaging of peripheral retinal lesions. Using a standardised technique, he presented beautiful images of peripheral retinal holes, tufts and lattice degeneration. This technique is useful when significant diagnostic uncertainty remains following clinical examination (for instance, differentiating a retinoschisis from retinal detachment).
Symptomatic Vitreomacular Adhesion
Results from the OASIS trial studying efficacy of intravitreal ocriplasmin was presented by Joseph Coney MD and Michael Tolentino MD. Overall, one-third of patients with symptomatic vitreomacular adhesion required vitrectomy by month six. A higher rate of VMA resolution (52 per cent) following intravitreal ocriplasmin was seen at day 28 than in the previous MIVI studies, predominantly due to a more selective population with smaller holes and no epiretinal membrane. Clement Chan MD, FACS showed good results of pneumatic vitreolysis for anomalous vitreomacular adhesion. A 0.2–0.3ml C3F8 gas bubble was injected in the eye. Success rates were 80 per cent for focal vitreomacular traction and 64 per cent for small stage two macular holes. Grazia Pertile MD and Zofia Michalewska MD, PhD discussed what they saw as benefits of performing an ‘inverted ILM’ flap technique to operate on macular holes, in contrast to the traditional technique of removing the entire internal limiting membrane around the hole.
Digital Assisted Vitreoretinal Surgery (e.g. Ngenuity) is a new system where two cameras acquire stereoscopic images that are visualised by the surgeon wearing 3D-spectacles on a high-definition television screen. The surgeon no longer has to look down an operating microscope. The main advantage is an ability to digitally modify the image to highlight specific tissues using digital filters. Lower light levels are required (minimising phototoxicity), since the exposure can be digitally enhanced.
A similar device (BEyeOnics) was presented by Adiel Barak MD. The benefits of intraoperative OCT during macular surgery were highlighted by Mark Barakat MD and Mehnz Khan MD. The main benefit was a better appreciation of the adequacy of membrane peeling at the time of surgery. A novel technique of ‘blindly’ repairing cyclodialysis clefts with 9-0 prolene sutures was described by Aleksandra Rachitskaya MD. Andre Principe de Oliveira MD discussed induction of posterior hyaloid separation from the macula without vitrectomy in patients with vitreomacular traction thought to be worsening AMD and CRVO. The main advantage of this technique is that it retains the vitreous reservoir and half-life of future anti-VEGF therapy. Jonathan Prenner MD showed a nice video demonstrating his technique of scleral sutured intraocular lens implantation using a 7-0 Gore-Tex suture and ‘cow-hitch’ knot giving two-point fixation on each haptic. In the RETINAWS instructional course, Kirk Packo MD discussed how he makes his own snare for removing large intraocular foreign bodies using a tuberculin syringe, 20-gauge blunt needle and 9-0 prolene suture. Abdallah Jeroudi MD presented a large retrospective case series of patients with retinoschisis. Outer wall breaks were found in 11 per cent of patients, and 28.6 per cent of these progressed to retinal detachment, slightly higher than previous literature had reported. Interestingly, he showed that wide field infrared imaging can help differentiate between the areas of retinal detachment (darker) and retinoschisis (lighter). Ehab El-Rayes MD, PhD presented four-year data on his technique of temporary scleral buckling by injecting Healon five in the suprachoroidal space. An experimental hypersonic vitrector was presented by Victor Gonzalez MD. This vitrector has cut rate speeds up to 1.7million cpm without increasing heat to unsafe levels.
Gene expression profiling is useful in prognosticating metastatic rates and survival in patients with uveal melanoma. Class two tumours have a much worse prognosis than class one tumours. Performing genetic testing can therefore help determine which patients are most appropriate to enroll in clinical trials of therapies for metastatic choroidal melanoma. Issues regarding genetic testing were discussed by Armin Afshar MD, Amy Schefler MD, Zelia Correa MD, PhD, Prithvi Mruthyunjaya MD and Bertil Damato MD, PhD. Tumours larger than 12mm in basal diameter were shown to have a worse prognosis. Timothy Murray MD demonstrated the off-label benefit of intravitreal aflibercept to treat radiation maculopathy, and Tara McCannel MD, PhD showed visual benefits of radiation attenuation by performing vitrectomy and silicone oil insertion at the time of plaque brachytherapy.
Hereditary Eye Disease
The retinal genetics instructional course led by Christine Kay MD discussed multimodal imaging to monitor the progression of hereditary eye disease. For instance, cone photoreceptor density can be measured by adaptive optics. The width of the healthy ellipsoid zone at the fovea is thought to be one of the most accurate parameters when determining progression of retinitis pigmentosa. Options for gene therapy include: replacement, addition (e.g. growth factors), neuromodulation (optogenetics), suppression (siRNA) and gene editing (CRISPR). Replacement is currently the most common option, using either viral (e.g. AAV) or nanoparticle vectors. Intravitreal and subretinal delivery is being explored, with the latter being more popular. MedOne Surgical Inc. now has a commercially available 1ml syringe that can attach to the VFC tubing to help with subretinal injection of gene vectors. Intraoperative OCT is useful in determining correct localisation in the subretinal space. An update of clinical gene therapy trials was presented, including for choroideremia, X-linked Retinoschisis, Achromatopsia and RPE65 Leber Congenital Amaurosis.
Dr Adrian Fung, MMBS (Hons), MMed (Ophthal Sci), MMed (Clin Epi), FRANZCO is a vitreoretinal surgeon and medical retinal specialist. He also has expertise in tumours of the retina and choroid. He trained at Sydney Eye Hospital before completing fellowships at the University of British Columbia, Vancouver, Canada; Manhattan Eye Ear & Throat Hospital, New York; Bascom Palmer Eye Institute, Miami and Wills Eye Hospital, Philadelphia, USA. He has published seven ophthalmic books or book chapters and over 40 peer-reviewed journal articles. Dr Fung is a Senior Clinical Lecturer at the University of Sydney and Macquarie University. He works privately at Retina & Macula Specialists (Miranda and Hurstville), Retina Associates (Chatswood, Bondi, Liverpool), Westmead and Macquarie University Hospitals.
Dr. Adrian Fung independently paid for all travel and accommodation costs to attend ASRS 2016. He has no relevant financial disclosures.