APVRS 2015 - Sydney, Australia - DAY 2 by Media MICE

APVRSSHOWDAILY Jul 31 – Aug 2, 2015

Sydney, Australia

The Official Conference News of APVRS 2015

Highlights

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Innovations in the retinal space have never been better.

Listening and Learning at the

APVRS

Opening Ceremony

techniques and imaging of the vitreo-retinal field has taken place, along with important intellectual exchanges in the Asia-Pacific region.

Tumors are under attack with posterior

segment oncology developments.

Day

After diabetic retinopathy, RVO is of great concern in retinal vascular disease. Published by:

Editorial Team Creative Content Director

Matt Young

Chief Editor

Gloria D. Gamat Project Manager

Hannah Nguyen Writers

John Kron, Claire Noonan, Ruchi Mahajan Ranga Designer

Winson Chua Photographer

Dwayne Foong

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by Matt Young

Attendees of the Asia-Pacific Vitreo-retina Society (APVRS) packed the room of the Opening Ceremony on Friday. Without a doubt, they gained valuable insights into the evolution of the APVRS, vitreo-retina surgery in AsiaPacific, and novel thoughts about related surgical issues. “We have over 1,100 registrants including industry,” beamed Dr. Andrew Chang, APVRS Congress Convenor. “There are 150 speakers from 20 countries.” The success of APVRS today largely is due to three individuals, he said. “The first is [Dr.] Yasuo Tano; he was a legend and he was visionary,” he said. “The second person is [Prof.] Dennis Lam. Dennis Lam makes things possible which appear impossible. He has taken APAO to great heights. He also is focusing his attention on APVRS. The third is [Prof.] Ian Constable. Ian is very softly spoken and polite. He came to me 2.5 years ago after a council meeting and

said, ‘Do you think we could have the meeting here [in Australia]? When Ian asks you to do something, you do it,” he quipped. Certainly, the importance of the APVRS organizer, speakers, exhibitors and, of course, attendees themselves, cannot be ignored in relation to the success of this Sydney meeting. Dr. Tasha Micheli, Chair of the New South Wales branch of RANZCO, said it well. “We are honored and privileged to have highly respected, internationally and locally renowned speakers to share their knowledge,” she said.

Prof. Tien Wong, Medical Director, Singapore National Eye Centre, gave the APVRS TANO Lecture. “We have seen significant progress on myopic CNV [in recent years],” Prof. Wong said. “But, what should we call this condition? Is it pathological myopia? Myopic retinopathy? Maybe ‘myopic macular degeneration’ is good to use because it has caught on with patients, governments and healthcare providers in understanding what we’re dealing with. It’s good to align the term so that myopic macular degeneration will catch people’s attention when we talk about this disease.”

PhotooftheDay

Prof. Xiaoxin Li, the APVRS President, meanwhile said history has contributed to the APVRS society’s success. “APVRS was founded in 2006 by Prof. Yasuo Tano together with the first council members,” she said. Over the last 8 years, the latest development in new drugs, surgeries,

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APVRSSHOWDAILY | Jul 31 – Aug 2, 2015 | Sydney, Australia

The Value of Aflibercept Across Retinal Diseases:

A Review of Evidence by Gloria D. Gamat

In Australia, aflibercept solution for injection (EYLEA, Bayer, Germany) is indicated for the treatment of several retinal diseases in adults: neovascular (wet) age-related macular degeneration (AMD), visual impairment due to macular edema secondary to central retinal vein occlusion (CRVO), and visual impairment due to diabetic macular edema (DME). Across these various retinal conditions, the value of aflibercept is rooted in its unique molecular design. “Specifically designed for strong, broad, and durable activity, aflibercept is a fusion protein for intravitreal injection Prof. Bora Eldem, symposium chairperson that ‘traps’ VEGF-A [vascular endothelial growth factor A] and PlGF [placenta growth factor] molecules,” emphasized Prof. Bora Eldem, M.D., FEBO, Professor of Ophthalmology, Hacettepe University, Ankara, Turkey. It [aflibercept] has a strict 1:1 binding ratio. This means that aflibercept–VEGF complexes do not link together via the VEGF dimer and most importantly, do not form multimeric conglomerates, which may aggregate and induce an immune response. Several studies have reported that PlGF have been found elevated in the vitreous and retina of patients and animals with diabetic retinopathy, thusly implicated in the pathogenesis of retinal disease. As reported by various clinical studies, aflibercept has been found to strongly inhibit VEGF (for almost twice as long as ranibizumab) and PlGF.

Aflibercept symposium panel of speakers

“The unique design of aflibercept allows for durable and broad intraocular activity, making it particularly suited for use within a treat-andextend regimen and it has the potential to minimize treatment burden,” concluded Dr. Eldem. Multiple clinical trials have demonstrated the efficacy of aflibercept across the retinal disease spectrum (AMD, DME and RVO).

Prof. Timothy Lai

“Treatments have resulted in rapid and robust visual gains that were maintained over extended periods,” explained Prof. Timothy Lai, MBBS(Sydney), MD(CUHK), MMedSc(HK), FRCS (Edin), FCOphth (HK), FHKAM (Ophth), Associate Professor, The Chinese University of Hong Kong, Hong Kong SAR, China. “Also, aflibercept is effective in the management of more difficult-to-treat disease subtypes including PCV and PED in wet AMD and ischemic RVO,” Dr. Lai added. The safety of aflibercept has been comprehensively assessed in large-scale studies with extended follow-up, and its systemic safety profile was evaluated using APTC-adjudicated criteria, reported Prof. Victor Chong, M.D., FRCS, FRCOphth, Professor, Oxford Eye

Hospital, United Kingdom. “A recent systematic review has assessed the safety of aflibercept across multiple indications and it was found well tolerated, with similar adverse effect (AE) rates to other anti-VEGF agents,” emphasized Dr. Chong. In clinical practice, despite the challenges of treating retinal disease, the real-world efficacy with EYLEA is similar to that seen in clinical trials, emphasized Prof. Sobha Sivaprasad, Professor, Moorfields Eye Hospital, London, United Kingdom. A question from the audience was directed to the panel of speakers regarding Protocol T and the difference between using 0.3 mg and 0.5 mg of ranibizumab, to which Prof. Sivaprasad replied: “The RISE & RIDE ranibizumab studies show that 0.3 mg is as effective as 0.5 mg and that there was no safety concern between the two [the FDA approved 0.3 mg].” “If there are no systematic differences between trials, we don’t expect any difference between 0.3 mg and 0.5 mg [in terms of safety or efficacy]; it should be similar,” she concluded.

APVRSSHOWDAILY | Jul 31 – Aug 2, 2015 | Sydney, Australia

Advances in

Pediatric Retinal Diseases by Claire Noonan

Retinopathy of prematurity (ROP) is a major cause of blindness. Early detection and treatment is vital, but the management challenges posed and lack of resources in some areas prevent optimal results. At the APVRS congress, speakers discussed the use of telemedicine in diagnosis, the promising nature of anti-VEGF in treatment of ROP and other topics of interest including the management of hereditary retinal diseases. ROP is the leading cause of childhood blindness. Around 30,000 children worldwide are blinded each year, due to ROP. The prevalence has increased due to improvement in the survival of children who are at risk.

If ROP is diagnosed early enough, treatments can help. Unfortunately there is lack of screening in many areas. Dr. Shuan Dai, MBBS, FRANZCO, Consultant Ophthalmologist and Senior Clinical Lecturer Dr. Shuan Dai at the University of Auckland and Auckland District Health Board, outlined strategies for improving early diagnosis. Screening programs need to ensure their own access, explained Dr Dai, for them to be worthwhile.

He explained the key to improving worldwide access to diagnostic services is to use a screening tool that can be operated by nurses or other allied health with the results then sent on to an ophthalmologist. For eight years he has worked with the Auckland Regional ROP service, a network of diagnostic coverage, which hasn’t missed a single at-risk baby. Results from this program show a decreased incidence of blindness. Dr. Pramod Bhende, MBBS, MS, ophthalmologist at Sankara Nethralaya in Chennai, India, discussed tips and

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APVRSSHOWDAILY | Jul 31 – Aug 2, 2015 | Sydney, Australia tricks for performing laser treatment of ROP. In performing this often tricky procedure, Dr. Bhende advised tactics such as using a higher table and waiting for a vantage position. Positioning the eye correctly and good pupil dilatation are helpful, as this procedure is ideally done in a single session under topical anaesthesia. Hope was offered for end-stage ROP by Prof. Rajvardhan Azad, MBBS, MD, FRCSed, FAMS, FICS, Professor and Retinal Surgeon at AIIMS. In advanced disease, surgical treatment can prevent progression. Improved outcomes have been demonstrated. However, there is a need for careful case selection for surgery. Technologies such as ultrasound biomicroscopy (UBM) aid surgical decision-making. UBM defines the surgical space- the critical gap between the retina and the lens.

One case Prof. Azad recalled - the surviving infant from a triplet birth made for a particularly special case of ROP requiring surgery. He showed a

video of the procedure to delegates, describing the care needed to avoid damaging the retina and lens. ‘’You can’t remove all the traction in one go,’’ he noted.

Retinoblastoma update Dr. Craig Donaldson, MB, BS, FRACS, FRANZCO, Paediatric Ophthalmologist, Children’s Hospital at Westmead, outlined how management of retinoblastoma has changed over the past 20 years. Less invasive tests are done now, including the use of specialized retinal imaging (RetCam). More invasive investigations are currently only done if there is clear evidence of spread. The classification system for retinoblastoma has changed. Groups A to E range from smaller in size up to a tumour that pushes on the back of the lens.

A small tumor can be managed with localized treatment, such as laser. For a larger tumor, chemotherapy may be used with the aim of shrinkage, but in such cases there is risk of recurrence, vitreous seeding or the development of other tumors, so additional focal therapy is usually implemented. For example, treatment of vitreous seeds can be performed by injection of melphalan into center of the vitreous jelly. Localized chemotherapy can also be delivered into the vitreous fluid, or directly into targeted arteries.

APVRSSHOWDAILY | Jul 31 – Aug 2, 2015 | Sydney, Australia

Inflammation Insights into the Retina by John Kron

Cytokines and other inflammatory markers may have an important role and provide insights into the management of diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). A study of 20 patients with DME who were unresponsive after three months of intravitreal bevacizumab were investigated with treatment with a corticosteroid, intravitreal triamcinolone, said Sohee Jeon, M.D., Ph.D., research fellow at the Department of Ophthalmology, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, South Korea. The study found that best-corrected visual acuity (BCVA) significantly improved after one and two months

but was not sustained at three months. However, central subfield thickness (CST) decreased 11% compared to baseline at one year. This improvement was associated with increased intraocular levels of the cytokine interleukin-8 (IL-8), according to Dr Jeon. “These results suggested that intravitreal triamcinolone may have a role in patients who are unresponsive to intravitreal bevacizumab in the short term,” she said. Treatment of PDR with anti-VEGF therapy may benefit from adjunctive therapy for potential fibrotic effects according to another study of inflammatory markers. The importance of researching this topic was emphasized by Xiaoxin Li, Dr. med., chairperson and professor of the

Eye Center and Eye Institute of Peking University People’s Hospital. “Does anti-VEGF therapy accelerate fibrosis in the retina is an important question,” she said. Scarring is necessary for treating choroidal neovascularization but the concern is whether there is “over-expression” that leads to fibrosis. Dr. Li described a study that investigated the epiretinal membranes of 14 patients proliferative diabetic retinopathy (PDR), dividing them into anti-VEGF treatment and non-treatment groups. The treatment group was found to have significantly greater levels of transforming growth factor beta (TGF-β), ciliary neurotrophic factor (CNTF) and connective tissue growth factor (CTGF), which can be associated with fibrotic effects.

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APVRSSHOWDAILY | Jul 31 – Aug 2, 2015 | Sydney, Australia

A Look into

theFuture by John Kron

of Retina

The future frontier of technology for the retina is an exciting field. A wide range of cutting edge innovations are driving the next wave of treatments for retinal disorders. A drug delivery system (DDS) for antiVEGF agents that provides a sustained and controlled delivery potentially offers an improvement to intravitreal injections, according to Jennifer KangMieler, Ph.D., associate professor of biomedical engineering, Armour College of Engineering, Illinois Institute of Technology, Chicago, USA. “The novel DDS utilizes microspheres of the drug embedded in a thermoresponsive hydrogel and is designed to increase the efficacy of the drug while reducing toxic effects,” said Dr. KangMieler. Two bionic devices showed benefits and good safety profiles. A suprachoroidal prosthesis was found to be safe and effective in a two-year study of three patients with end-stage retinitis pigmentosa (RP) who had a guide dog for navigation vision, said Penelope Allen, M.D., Ph.D., program leader of the surgical program at Bionic Vision Australia and ophthalmologist in the medical and vitreoretinal unit at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia. The prosthesis is made up of 24 stimulating electrodes made of platinum and silicone; no additional electronics are required. The study found the surgery to insert the prosthesis was “straightforward and safe.” After two years it proved to be stable and didn’t lose electronic function, provided reliable phosphenes, generated phosphene maps,

demonstrated functional vision testing and, as shown in video footage, enabled navigation vision without a blind dog. A recent meeting in Ann Arbor, Michigan, USA, of ophthalmologists and allied healthcare professionals from around the world provided feedback of the experiences of 130 patients using the Argus II Implantation, said Thiran Jayasundera, M.D., FACS, FRCSC, FRANZCO, assistant professor, ophthalmology and visual sciences, from the University of Michigan. The Argus II Implantation is a “headmounted video camera that has wireless communication with an array implanted on the retina” that is indicated for retinal peripheral degeneration disorders such as RP. The meeting concluded that the experiences have been “very promising but also have challenges.” The promising results include enabling patients to walk unassisted and pick up objects such as cups and bowls at home, while the challenges range from adverse events due to surgical implantation such as conjunctival erosion and ensuring effective clinical visual rehabilitation. Gene-based therapy also offers hope of therapeutic benefits. A trial of a tyrosine kinase VEGF1 receptor variant injected under the retina for 27 patients with wet AMD had positive initial results. While still being analysed and commercially

confidential, Ian Constable, AO, MB BS Syd., FRCSEd, FRACO, FRACS, professor of ophthalmology, from the Centre for Ophthalmology and Visual Sciences at the University of Western Australia, Perth, Australia, said there was a good safety profile and a majority of patients achieved therapeutic responses. Stem cell therapy is being tested on retinitis pigmentosa. Induced pluripotent stem cells (iPSC), which were adult stem cells taken from the skin and blood and then treated in a culture to enable them to be differentiated into rod photoreceptor cells, said Yoko Ozawa, M.D., Ph.D., chief of Laboratory of Retinal Cell Biology and assistant professor, Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan. Nanosecond laser, which is laser therapy given in 3 nanosecond pulses, was found to be effective in 40% of 50 patients with intermediate AMD for reducing drusen workload as well as improving visual function in a one-year pilot study. Robyn Guymer, MBBS, PhD, FRANZCO, head of Macular Research and deputy director, Centre for Eye Research Australia (CERA), Royal Victorian Eye and Ear Hospital, Melbourne, Australia, said while the study didn’t make conclusions on stopping end-stage AMD, an animal study on induced AMD had found reduction in retinal thickness.

APVRSSHOWDAILY | Jul 31 – Aug 2, 2015 | Sydney, Australia

Posterior Segment Oncology in Focus by John Kron

Oncology of the posterior segment of the eye is a field undergoing continuing updates of interest to both the general ophthalmologist and oncology ophthalmologist.

see definite growth,” said Prof. William Campbell, M.D., Ph.D, Head of Vitreoretinal Unit, at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia.

The overall benefits also include imaging medium to large tumors where you can see them in one field, angiography of Prof. William Campbell Wide field imaging peripheral vascular lesions has improved the ability to assess and evaluating the extent of ischemia in tumors such as choroidal melanomas radiation retinopathy. compared to the standard fundus camera. “With the standard fundus Steering away from the emphasis of camera it may be hard to see if a lesion radiology, Michael Giblin, MBBS (Hons) is growing or not, but when you take (Syd), FRACO, FRACS, Clinical Senior photographs with a wide-angled Lecturer at Clinical Ophthalmology camera over a period of time you can & Eye Health, Central Clinical School,

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University of Sydney, discussed the pitfalls and errors in the diagnosis of tumors such as choroidal melanoma. Talking about optical coherence tomography (OCT), he said: “It is very useful, we all love it. But it mustn’t serve as an alternative or substitute for a sound clinical examination. For example, OCT shows evidence of sub-retinal fluid in 20% of cases of patients with choroidal nevi but that’s not necessarily a clinically significant finding.” The importance of accurate diagnosis, specifically in relation to ocular lyphoma was also spoken about by Dr. Peter McCluskey, Professor of Clinical Ophthalmology and Eye Health and Director of Save Sight Institute, University of Sydney, Australia.

APVRSSHOWDAILY | Jul 31 – Aug 2, 2015 | Sydney, Australia “Ocular lymphoma has been steadily increasing over the past 40 years by about 3 to 5%, so it’s becoming an increasingly common disorder that we need to recognise and treat. It used to be a disease you used to see in old people, essentially with anybody aged over 40. We need to think [whether] their inflammatory symptoms in the eye be a masquerade and be a lymphoma,” he said. “A high index of suspicion” should be actively pursued with accurate tissue diagnosis with multiple surgical procedures available. Management of tumors may include observation as well as active treatment such as with vascular tumors of retina and choroid, said Adrian Fung, MBBS(Hons I), MMed(Ophthalmic Science), MMed(Clinical Epidemiology), FRANZCO, Vitreoretinal Surgeon at

Sydney Eye Hospital Retinal Unit and Clinical Senior Lecturer at Clinical Ophthalmology & Eye Health, University of Sydney, Australia. These tumors include choroidal haemangiomas, Coat’s Disease, retinal capillary haemangioblastomas and vasoproliferative tumors. Choroidal haemangiomas, for example, can be divided into circumscribed and diffuse lesions. The circumscribed lesions are benign lesions that can “often lie asymptomatic for long periods of time” unless there is fluid accumulation due to leakage of the tumor, which can cause loss of vision and then needs to be treated with photo dynamic therapy (PDT). Endoresection surgery provides a safe and effective alternative treatment option for ocular tumors in patients

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who have had brachytherapy but subsequently had recurrent growth or complications such as retinal detachment, according to Dr. Gerard McGowan, a vitreoretinal surgeon at the Tennent Institute, Glasgow, United Kingdom. Dr. McGowan presented a series of eight case studies from 2008 to 2014 whom mostly had large tumors and received endoresection at an average of 42 months post-commencement of brachytherapy. As shown in a video presentation, the procedure involved cutting out the core of the tumor and using a diode laser to destroy the remnant cells. The follow up results have been largely positive with six patients maintaining vision and one patient with improved vision and no recurrences, metastases or deaths reported.

APVRSSHOWDAILY | Jul 31 – Aug 2, 2015 | Sydney, Australia

Improving management of PCV by John Kron

Insights into the diagnosis and treatment of polypoidal choroidal vasculopathy (PCV) were provided by Colin Tan, MBBS, FRCSEd (Ophth), MMed (Ophth), Senior Consultant Ophthalmologist and Clinician-Researcher from the Department of Ophthalmology, Tan Tock Seng Hospital, Singapore. PCV is a disorder characterized by serosanguineous detachments of the pigmented epithelium and exudative changes that is found in up to 55% patients with age-related macular degeneration (AMD) and has high prevalence amongst Asians, noted Dr. Tan. The recommended diagnostic technique is indocyanine green angiography (ICGA). However, ICGA isn’t always available in all healthcare centers and it may also be contraindicated in some patients, he said.

Fluorescein angiography (FA), which can be more readily available, may provide an effective alternative that provides a high level of suspicion that can be followed up with ICGA. Dr. Tan described a prospective study of PCV patients that identified three FA features that indicated PCV, including: nodular hyperfluorescence, occult choroidal neovascularization and blocked fluorescence. In a second study of 107 patients, a classification system was identified that found three subtypes that correlated with long-term outcomes. FA and ICGA were used to describe angiographic features based on leakage and branching vascular patterns. The three subtypes were: type A (interconnecting channels) 22.4%; type B (branching vascular network) 24.3%;

type C (active leakage) 53.3%. Type C was found to have the higher rates of angiographic leakage and poorer long term visual outcomes. At five years good visual outcomes (≥6/12) were highest in type A, compared to type B and C (80% v 66.7% v 7.7%, P<0.001). Dr. Tan also described a study of 100 healthy volunteers that provided an equation to take into account the different results of retinal thickness obtained through two OCT imaging machines, Spectralis and Stratus, on the same patients. The differences can, on average, be 77 µm. The equation was able to provide consistency, which may be of benefit when reviewing past cases and conducting multicenter trials.

APVRSSHOWDAILY | Jul 31 – Aug 2, 2015 | Sydney, Australia

Clinical Applications of Imaging

Modalities

by Claire Noonan

The Heidelberg Engineering Symposium at the APVRS congress in Sydney provided an opportunity for delegates to become more familiar with the applications of promising new retinal imaging technology. Associate Professor Wilson Heriot of the University of Melbourne’s Department of Ophthalmology began the session with a discussion about ICG imagery of polypoidal choroidal vasculopathy (PCV). He explained that understanding of the condition has evolved from the earlier conceptions of subretinal bleeding that was more prevalent in certain racial groups. He stated that PCV is a condition that is often missed, as it’s only visible on Indocyanine Green Chorioangiography. Since this imaging has become more widely used, the incidence of PCV has appeared to increase, due to higher rates of recognition. Associate Professor Heriot added that there are presumably many asymptomatic cases, so we can’t truly know the incidence. He added that “it truly is an enigmatic disease” that can pose a dilemma of therapeutic choicewhether to treat with anti-VEGF alone or otherwise. Dr. Praveen Patel, Consultant Opthalmologist from Moorfields Eye Hospital in London, stated it is thanks to the development of retinal imaging technologies that progress has been made beyond anti-VEGF treatments and onto such modalities as gene therapy, stem cell therapy and retinal prostheses. Fundus photography has evolved further, culminating in the Spectralis system, allowing more accurate diagnosis, discovery of new diseases and providing more insight into treatment impacts on retinal structures.

ICGA and OCT

He explained that in the SPECTRALIS system, images gained from the reflection of three different wavelengths (blue, green and infrared) are combined, giving a crisp image with less noise than in some other modalities. Each wavelength penetrates to different layers in the retina, allowing examination of 3D structures such as retinal microvasculature. Some of the clinical applications of SPECTRALIS were outlined by Dr Patel. He showed delegates Spectralis imaging of a choroidal naevus, showing how infrared light was reflected by the particular melanin involved. Conversely, in conditions leading to macular oedema, infrared light is absorbed rather than reflected, leading to a green appearance. Compared with traditional fundography it is easier to make out Central Serous Chorioretinopathy with multicolour imaging. Separating images from the three colour channels can enhance interpretation. For example, on the green channel, haemorrhages of diabetic retinopathy are apparent as haemoglobin absorbs green light.

However, other conditions are better visualised with multicolor imaging, such as dry AMD - where, says Dr Patel - we can “interrogate the edges of the lesion.” MultiColor images can even be obtained in cases of patients with nystagmus or lens opacity. He iterated the need for many imaging modalities in addition to Spectralis. “The right scan in the right patient yields the diagnosis,” he said. Dr. Fred Chen, opthalmologist and researcher in the Ocular Tissue Engineering Lab at the Lion’s Eye Institute in Perth, discussed OCT angiography, particularly motion brightness scans. Twenty five frames per second are taken at each location, creating a map of intensity variation. This is useful in isolating structures within the retina, such as capillary network. Spectralis’s options also include multiple laser fundus imaging modalities, widefield and ultra-widefield modules, and scanning laser angiography. The latter may be done with fluorescein or ICG dye, using a smaller volume of dye than in traditional fundus photography.

APVRSSHOWDAILY | Jul 31 – Aug 2, 2015 | Sydney, Australia

Superior Pharma and Imaging Devices Discussed by John Kron

Aflibercept may provide an alternative treatment option for patients with wet age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) who are refractive to other anti-VEGF therapies, said Prof. OhWoong Kwon, M.D., Ph.D., Head Professor of Ophthalmology, Yonsei University Medical School, Seoul, South Korea. Prof. Kwon’s talk, as well as others focused on new treatments and devices, formed part of Rapid Fire Vitreo-retina Update Session 1 on Friday. A retrospective study of 29 patients with AMD or PCV found patients who switched over from other anti-VEGF therapies to aflibercept had improvements of bestcorrected visual acuity (BCVA) during 5.5 months from 0.58 to 0.55 (P=0.005) and central macular thickness (CMT) from 404 to 321 µm.

The patients who continued aflibercept sustained their improvements; however those who switched back to bevacizumab worsened, suggesting that the latter may not be a proper treatment approach, said Dr. Kwon. Meanwhile, Ocriplasmin, a relatively new recombinant protease drug for vitreomacular traction (VMT), has a good safety profile based on a large body of data from clinical trials and post-marketing research, including approximately 1,300 and 14,000 eyes respectively, said Prof. Jagjit Singh Gilhotra, MB, BS, M. Med, FRANZCO, Associate Professor, South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia. The post-marketing data is consistent with the phase III clinical trials and further demonstrates that there is no change in the favourable benefit to risk profiles of the drug, said Dr. Singh Gilhotra.

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The most common adverse event was visual impairment; 14% and 2.3% in clinical trials and post-marketing data. A study of 65 patients with high myopia and retinoschisis on B-scan who were investigated using wide field scans with swept-source optical coherence tomography (SS-OCT) that provided 3-D visualization of pathological features was described by Prof. Mingguang He, M.D., Ph.D., Professor of Ophthalmic Epidemiology, University of Melbourne, Melbourne, Australia. The study identified three types of retinoschisis based on layers, said Dr. He. The most superficial layer was within the retinal nerve fiber layer (intra-RNFL), the intermediate layer was beneath the RNFL (sub-RNFL) and the deepest was within the outer plexiform layer (intraOPL). It was found that sub-RNFL was the most affected (94%) by retinoschisis compared to the other layers, he said.

APVRSSHOWDAILY | Jul 31 – Aug 2, 2015 | Sydney, Australia

Controversies and Developments in... by Claire Noonan

The incidence of retinal vein occlusion (RVO) is increasing. It is the second most prevalent cause of retinal vascular disease after diabetic retinopathy. Therapeutic options for patients with RVO each have their pros and cons. At the APVRS congress today speakers at the symposium on RVO and other retinal vasculopathies discussed the latest evidence and new directions. The chief causative factors of RVO are age and cardiovascular risk, though recently dehydration as a cause has been postulated. With today’s trends of intense exercise and intermittent fasting diets, dehydration can leave the blood more viscous, leading to a higher likelihood of venous occlusion, though evidence is scant so far, says Sobha Sivaprasad, MBBS, MS, DM, FRCS, FRCOphth, Professor and Consultant Ophthalmologist at Moorfield’s Eye Hospital and Kings College Hospital, United Kingdom. ‘Since the Royal College guidelines for managing RVO came out ten years ago, the protocol has evolved from extensive testing for all possible underlying causes, to just the basic tests: blood pressure, blood sugar levels, ESR and FBC, as the majority of cases (around 99%) are caused by arteriosclerosis,” explained Prof. Sivaprasad. If cardiovascular risk factors are not present, then the rarer causes such as a thrombophilia or an inflammatory condition, can be considered. Another major change is that aspirin is no longer routinely given as Prof. Sivaprasad explains evidence has shown ‘it does not prevent contralateral or recurrent RVO’. The use of imaging in diagnosis and classification of RVO was also discussed by Prof. Sivaprasad. In a study by

Kaines and colleagues, some cases that appeared to be non-ischemic on a 7-field image had clear areas of non perfusion when viewed with wide field angiography. The usefulness of wide field imaging was further discussed by Ian McAllister, MBBS W.Aust., FRACS, FRACO, Professor of Ophthalmology and Director, Clinical Services, Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, who explored the features of different imaging modalities and the benefits of each with regard to visualizing aspects of RVO. There has been ongoing and exciting developments in imaging, leading up to SPECTRALIS, which, as Prof. McAllister noted, is a multimodal system and one whose images we are still learning how to read. A key feature in RVO is macular edema, the leading cause of visual loss in RVO. Also, VEGF is upregulated in the ischemic retina. Prof. McAllister reminded the congress that increased VEGF brings with it ‘devastating consequences’. He commented that Anti-VEGF seems to be useful in decreasing the incidence of capillary non-perfusion, as found by Campochiaro and colleagues (Ophthalmology 2012). It can also increase visual acuity. Findings were consistent across study arms: when the patients who started on placebo were later given anti VEGF the same good effect was observed. Prof. McAllister called for further studies to see if anti-VEGF administration can prevent perfused cases from progressing to a non-perfused state. ‘We need more data to understand the protective effect’, he concluded.

RVO Hyung Chan Kim, M.D., professor and chairman of the Department of Ophthalmology at KonKuk University Medical Centre, South Korea, outlined the indications for steroid treatment, such as those patients in whom antiVEGF is contraindicated, or those who are non-responders to anti-VEGF. Due to the short half life of dexamethasone injections, he explained that an implant drug delivery system is invaluable for these patients.

“Sequential or combination treatments for RVO is an option the cost of treatments are prohibitive in some countries, necessitating clear evidence for their use,” said Ian Wong, FRCOphth, FRCS (Edinburgh), FHKAM (Oph), FCOphthHK, M.Med (Singapore), MBBS(HKU), Clinical Assistant Professor, University of Hong Kong. Discussing the option of starting a patient on antiVEGF for the rapid onset benefit, followed by a dexamethasone implant to give improved visual acuity and better resolution of macular edema: “Future studies should look at the ideal interval between the treatment steps and assess any difference in response between ischemic and non-ischemic RVO cases,” said Dr. Wong. On the other hand, Victor Chong, M.D., FRCS, FRCOphth, clinical senior lecturer at the University of Oxford Eye Hospital, mentioned novel treatments targeting RVO that may ease the treatment burden, such as panretinal photocoagulation and laser induced venous bypass. He gave the congress a message of hope: ‘the ischemic retina can indeed recanalize’.

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Seeing is Believing Patient 1: 54-year-old with CSR who had a history of bullous CSR and a large persistent neurosensory detachment.* * BEFORE

AFTER

VA 20/200 | CMT 640 µm

4 mos post MicroPulse | VA 20/25 | CMT 204 µm (Complete resolution of subretinal fluid)

Patient 2: 59-year-old with a history of chronic (>10 years) unresolved subretinal fluid involving the fovea. As an artist, this patient desired distortion-free vision. BEFORE

AFTER

VA 20/40-2

4 wks Post MicroPulse | VA 20/30+ (Resolution of subfoveal fluid)

Photos courtesy of Gennady Landa, MD. Learn More about MicroPulse

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Gennady Landa, MD. New York Eye and Ear Infirmary, Mount Sinai, New York, NY * Bhagat N, Zarbin M, Mansour S, Chong V, and Cardillo JA. Fovea-friendly MicroPulse Laser. Supplement to Retina Today, May/June 2012 ** IRIDEX lasers are cleared for retinal photocoagulation of vascular and structural abnormalities of the retina and choroid; and iridotomy, iridectomy and trabeculoplasty in angle-closure glaucoma and open-angle glaucoma.

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