ASIA-PACIFIC’S FIRST MAGAZINE ON THE POSTERIOR SEGMENT
THE GOLD ISSUE December/January 2019 APVRS 2018 Seoul Edition
posterior segment • innovation • enlightenment
Gene and Drug Delivery for Retinal Diseases:
What’s Next? Page
Robots May Soon Take Over Surgeries... and the World! Page
The of Vitreoretinal Surgery
THE WORLD’S FIRST FUNKY OPHTHALMOLOGY MAGAZINE
Inside this issue...
Posterior Segment page page
Déjà Vu: Secondary Glaucoma after Pars Plana Vitrectomy
Alcon’s NGENUITY Revolutionizes Surgery with Greater Depth and Visualization
Posterior Segment Complications of Cataract Surgery
Revelations in Vitreoretinal Surgery
Gene and Drug Delivery for Retinal Diseases: What’s Next?
Aflibercept Receives Approval for Proactive Treat-and-Extend Regimen
Vitreoretinal surgeons explore their views on what is “gold,” and discuss what is needed to raise that benchmark even higher.
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PIE MAGAZINE LETTER TO READERS
Dear Reader, “G
It’s a term that has been thrown around abstractly in ophthalmology to address the pinnacle of contemporary treatment options. And yet, the color of gold is so vibrant. Immediately, we could easily recollect the appearance of luxurious jewelry, gold coins (chocolate-filled or otherwise), gold bricks, or if you consider yourself to be a golden goose of sorts, the eggs you lay. And yet, the gold standard can be elusive in ophthalmology. In the field of glaucoma, one might say Goldmann tonometry is the gold standard of IOP measurement. But is trabeculectomy still the gold standard of glaucoma surgery? If your answer is yes, in our MIGS era, what would be the watershed moment defining a new gold standard? What evidence would you need to view such a transition come to light? Sometimes, the industry has influenced this golden notion. Pharmacological guidelines have been developed on more than one occasion to influence a sense of standardized treatment - which could be seen as having at least a silver value if not gold. Scientific perception can be managed in peer review or a high level roundtable or conference venue. Ultimately, the gold standard still is judged by each practitioner on its own merits. One high level retinal specialist assured us that he would no longer operate without 3D visualization. Certainly to him, that had become his gold standard. Hence, we talked to modern retinal specialists about what today is the gold standard for them. Their stories won’t be your stories, but we hope it challenges you to think more than concretely about what is your gold standard among various treatment options today. After all, what is gold at its core? It’s something of inherently and incredibly high value. It stands the test of time. It is reliable, and it also has a value that the community at large can agree on. Obviously, when it comes to surgery, patient sight is in your hands. In challenging surgical circumstances, wouldn’t you want to have the gold of standards available to you? We encourage you to take time and reflect on your pharmaceuticals, lasers and surgical procedures, and for various areas of treatment, to clearly paint a picture of your gold standards. In difficult times - from surgical to even unfortunate legal circumstances - you will be glad you took time out for this colorful, powerful review of your armamentarium. We hope you enjoy our PIE 08 Cover Story on this topic. And meanwhile, this issue brings to a close two full years of PIE Magazine issues. We most appreciate you as a reader of our uniquely colorful ophthalmic material, and we wish you many golden opportunities to come in 2019 and beyond.
Matt Young CEO & Publisher PIE (Posterior Segment - Innovation - Enlightenment) Magazine
PIE MAGAZINE ADVISORY BOARD MEMBERS Dr. Gemmy Cheung, MBBS(Lond), FRCOphth(UK) Dr. Cheung currently serves as deputy head and senior consultant of the medial retina service for Singapore National Eye Centre (SNEC), as well as senior clinician investigator for the Singapore Eye Research Institute (SERI). Her research interests include the study of risk factors and clinical features of macular diseases that may be unique in Asian populations. Dr. Cheung has published more than 150 articles, mostly regarding age-related macular degeneration, including polypoidal choroidal vasculopathy, and conducted several clinical trials in anti-vascular endothelial growth factor therapies. Dr. Cheung has also been actively involved in training and education, and has served as an instructor on Asia-Pacific Academy of Ophthalmology (APAO) and American Academy of Ophthalmology (AAO) courses and many other educational programmes. In addition, she is also a volunteer faculty member for the ORBIS Flying Eye Hospital Programme. Dr. Cheung has received a number of prestigious awards, including the Macula Society Young Investigator Award (2017), APAO achievement award (2017), APAO Nakajima Award (2014), APAO Outstanding Service in Prevention of Blindness Award (2013), the Bayer Global Ophthalmology Research Award (2012), the Roper-Hall Medal (2005) and the Elizabeth Hunt Medal (Royal College of Ophthalmologists, UK). [Email: email@example.com]
Prof. Mark Gillies, M.D., Ph.D. Dr. Gillies presently holds a number of positions including: director of research and director of the Macula Research Group for the Save Sight Institute; foundation fellow for the Sydney Medical School; professor in the Department of Clinical Ophthalmology at the University of Sydney; head of the Medical Retina Unit at the Sydney Eye Hospital; deputy chair for the Ophthalmic Research Institute of Australia; and director of Eye Associates in Sydney. Dr. Gillies has served as a principal investigator or associate investigator in more than 70 clinical trials, and his research regarding macular degeneration and drug safety and efficacy has been published in 188 journals. He has also received a number of grants to study treatments for age-related macular degeneration, retinal disease and Muller cell dysfunction â€“ among other treatments and studies. Dr. Gillies has also appeared in national media on numerous occasions, including the evening news of all major networks, on ABC radio as a local expert, as well as in print media. His dedication and research has resulted in multiple awards. Most recently, he received Gerard Crock trophies for the best papers at the Royal Australian and New Zealand College of Ophthalmologists (RANZCO) Annual Scientific Meeting (2013 and 2015), an achievement award from the Asia-Pacific Academy of Ophthalmology (APAO) in 2014, and an achievement award from the American Academy of Ophthalmology (AAO) in 2015. [Email: firstname.lastname@example.org]
Dr. Vishali Gupta, M.D. Dr. Gupta currently serves as a professor of ophthalmology at Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh in India. Throughout her career, she has completed original work in the fields of intraocular tuberculosis, optical coherence tomography, diabetic retinopathy, and fungal endophthalmitis. In addition, she is actively studying vitreoretina and uveitis diseases. She has been published in 65 per-reviewed journals, and has authored 17 book chapters and four complete books. Dr. Gupta also holds a US patent for the development of multiplex PCR for uveitis. In addition, she is a sought after speaker, and has made more than 350 presentations in various national and international meetings. Dr. Gupta has received several awards for her work, including the first JN Pahwa award from the Vitreo Retinal Society of India, the first NA Rao Award from the Uveitis Society of India, and the first NA Rao award from All India Ophthalmological Society (AIOS). [Email: email@example.com]
POSTERIOR SEGMENT RETINAL COMORBIDITIES
Secondary Glaucoma after Pars Plana Vitrectomy
Elevated IOP after PPV seems to keep happening
by Dr. Sahebaan Sethi and Joanna Lee
What should doctors be watchful for after a pars plana vitrectomy (PPV)? Dr. Sahebaan Sethi takes us through an insightful overview surrounding PPV with research and from her own experience in the field. The clinical pearls shared below highlight the importance of working with retinal specialists to effectively address secondary glaucoma post-PPV.
ecause of increased retinal comorbidities in the older population, it’s crucial that glaucoma specialists work in close collaboration with retinal surgeons. Often, there are patients with increased pressure following vitreoretinal surgeries, and this can happen anytime during the postoperative period. Moreover, detecting glaucomatous damage may be difficult when the underlying retinal disorder precludes accurate assessments of visual fields or the optic nerve. PPV is done for several reasons — vitreous hemorrhage, macular holes, epiretinal membranes, retinal detachment repair and proliferative diabetic retinopathy. During the procedure, substitutes like heavy liquid (perfluorocarbon), intraocular gases, or silicone oil (SO) may be used. Heavy liquid is usually removed at the time
of the surgery; however, other internal tamponade agents may be present for weeks to several months. Often, patients with high risk of redetachment may require the tamponade for longer periods of time and the retinal surgeon might opt not to remove it – thus, compromising the aqueous outflow in several ways, which results in increased intraocular pressure (IOP).
Incidence IOP elevation is the most common complication following PPV surgery. The reported incidence of postoperative glaucoma ranges from 20%-26%.1,2,3 In a prospective study of 222 cases, an IOP rise of 5 to 22 mm Hg during the first 24 hours occurred in 61% of eyes and an increase of 30 mm Hg occurred in 35%.4 Koreen et al.5 observed a 11.6% incidence in late-
onset open angle glaucoma among 285 vitrectomized eyes, although rates were higher in eyes that had undergone cataract extraction (15.0%) versus phakic eyes (1.4%). These rates are similar to those reported by Luk et al.6 More recently, a retrospective study by Wu et al.7 examined 198 patients and found that elevated IOP incidences were 19.2% in vitrectomized eyes, compared with 4.5% in the unoperated fellow eye. It’s safe to say that these findings show PPV is a risk factor for secondary glaucoma.
Evaluation It is important to routinely monitor patients’ postoperative IOP, which is best done by applanation tonometry (indentation tonometers are unreliable due to scleral surgery and intraocular gas interfering with scleral rigidity). One study found that pneumatic tonometry and indentation tonometry underestimated the elevated IOP by 25% and 79% respectively (Poliner LS and Schoch LH, 1987). Tonopen is also an acceptable means, although it underestimates the IOP if it’s above 30 mm Hg.
Pathogenesis We approach glaucoma according to its presentation, which could either be open-angle or closed-angle glaucoma. The possibilities for open-angle include gas expansion without angle closure — this is the most common cause of acute post-vitrectomy IOP elevation, along with inflammation, silicone oil (sans pupillary block), corticosteroid response and blood mediated mechanism (hyphema, ghost cell or hemolytic).8 The mechanisms for closedangle glaucoma include ciliary body edema causing pupillary block (the most common mechanism), followed in descending order by pupillary block secondary to fibrin, gas, and lastly silicone oil.9
Secondary glaucoma due to intraocular gas injection The incidence of high IOP after PPV and long-acting gas tamponade was established by a report that found a 43% incidence of pressures greater than 25 mmHg.9 Sulfur hexafluoride can remain in the eye for 10 to 14 days and up to 55 to 65 days for perfluoropropane.10 Elevated IOP is generally due to an intraocular gas bubble, which causes open-angle glaucoma. Frequently, there is a secondary angle closure pathology – this is due to posterior pressure of the gas on the iris, which causes the angle to narrow. This is well demonstrated in the aphakic patient, who can relieve the pupillary block by posturing face down. It could also be a result of ciliary body edema and iridocorneal apposition. Risk factors that would predispose a patient to an acute increase in IOP after gas tamponade include the concentration of the gas; patient’s older age; post-operative fibrin in the anterior chamber; concurrent use of a scleral buckle; and use of intraoperative endophotocoagulation.11,12 There are a few points of caution when dealing with this type of patient. They should avoid inhaling any of the nitrous oxide anesthetic during a dental
visit or with general anesthesia. This gas diffuses rapidly and causes rapid expansion of the gas bubble, causing IOP to skyrocket as high as 70 mmHg, leading to retinal artery occlusion and ischemia. Generally, it’s suggested that these patients do not increase their elevation by 2,500 feet or travel by air where changes in the cabin pressure can instantaneously cause severe elevation of IOP.13 In Dr. Sethi’s experience, any immediate acute rise in IOP postoperatively can be controlled with topical anti-glaucoma medications and oral carbonic anhydrase inhibitors. However, if the IOPs remain uncontrolled, an anterior chamber paracentesis may help, or a small volume of gas may be aspirated from the vitreal cavity with a 27G needle and a 1ml syringe. Prudent vitreo-retinal surgeons use prophylactic treatment with intraoperative carbonic anhydrase, as this may control the post-operative pressure spike.
Elevated IOP and silicon oil Reported rates of chronic elevated IOP following use of silicone oil vary enormously—from 2.2 percent to 56 percent.14-16 Risk factors for developing high pressure after silicone oil include: silicone oil in the anterior chamber; preexisting glaucoma; aphakia; early postoperative pressure spike; trauma; diabetes; and postoperative neovascularization of the iris. Elevated IOP can occur via several mechanisms− acute angle closure with or without pupillary block; open-angle glaucoma with emulsified or nonemulsified silicone oil in the anterior chamber; continuing rubeosis of the iris leading to secondary angle closure; or simple idiopathic open-angle glaucoma. The incidence of acute angle closure with pupillary block has dropped dramatically since retinal surgeons have begun creating a prophylactic inferior peripheral iridotomies (PI) at the time of surgery. However, these iridotomies may still close spontaneously.17,18
Also, angle closure with pupillary block is more likely if the patient is aphakic. If the PI closes it may be reopened with the Nd YAG. However, Nd YAG laser PI can have a high rate of failure of 78% in reopening inferior PIs (Reddy, 1995). At one time, it was thought that whenever silicone oil made it into the anterior chamber, IOP would surely rise; however, various studies have shown that high IOP may occur with or without oil in the anterior chamber.19, 20, 21, 22 Management of these patients can be quite tricky. Frequently, removal of the silicone oil may not be enough to resolve the underlying problem; for that reason, it remains a controversial way to control glaucoma. It was reported that removal of the emulsified oil didn’t change the IOP in 91% of subjects.23 In another study, silicone oil removal and medications produced pressure control in only 25% of patients.17 Another study found that patients who underwent silicone oil removal, with or without glaucoma surgery, and those who underwent glaucoma surgery alone, experienced satisfactory IOP control.24 Surgical management of these patients should be closely discussed with retinal surgeons. This is because removing the silicone oil may not always be possible as it’s associated with re-detachment in 11 to 33% eyes.17 If the retina surgeon feels that it’s safe to remove the oil, then, Dr. Sethi says she would proceed with its removal and simultaneous placement of a glaucoma drainage device; glaucoma drainage implants can control the IOP in the majority of eyes after PPV and silicone oil injection.25 Removal of silicone oil alone does not allow eyes to achieve normal IOP. If the retinal surgeon feels the oil needs to remain in the eye for a longer period, and aqueous suppressants are not effective, a glaucoma drainage implant in an inferior quadrant or a trans-scleral diode cycloablation could be considered. According to Kim and Baumal, topical and systemic anti-glaucoma medications controlled IOP in 30% of eyes (mean number of medications:
POSTERIOR SEGMENT RETINAL COMORBIDITIES References: 1.5), with oral acetazolamide required in 7/18 cases.26 Fifty percent of the eyes required chronic glaucoma treatment. Removal of SO and medical therapy (25%) achieved normal IOPs. Control of IOPs were achieved in 10/14 eyes that underwent surgical intervention. Five of 14 that underwent trabeculectomy with mitomycin C achieved normal IOP (two cases with additional medical therapy and one with surgery alone, post ROSO). In the same study, one patient had an anterior chamber tube shunt to the encircling band (ACTSEB) and achieved normal IOP with additional medical therapy. Three patients underwent cyclocryotherapy, with 33% achieving normal IOP without and 33.3% with medical therapy. Four patients underwent transcleral cyclophotocoagulation with a 75% success rate of controlling the IOP. In patients with SO induced glaucoma, removal of the oil may reduce the IOP. If the oil is not removed before tube glaucoma surgery, migration of oil into tube can occur, even if it is placed inferiorly, with the hope that the oil will float and not occlude the tube. Transscleral cyclophotocoagulation has shown successful IOP control in 74-82% of patients after 1 year although the visual function was poor in these patients (Bloom et al 1997 and Han et al, 1999).27 Early removal of silicone oil has been noted to have reduced risk of secondary glaucoma and similar re-detachment rates (Han et al., 1998).
Conclusion Secondary glaucoma post-PPV may be one of the most refractory cases to deal with and presents a challenge to both glaucoma and retinal specialists. The causes may be multi-factorial and management depends entirely on the mechanism of glaucoma. Patients with whom aggressive medical management is unsatisfactory, may benefit from silicone oil removal, glaucoma drainage devices or cyclodestructive procedures.
Faulborn J, Conway BP, Machemer R. Surgical complications of pars plana vitreous surgery. Ophthalmology. 1978;85(2):116-125. 2 Aaberg TM, Van Horn DL. Late complications of pars plana vitreous surgery. Ophthalmology. 1978;85(2):126-140. 3 Ghartey KN, Tolentino FI, Freeman HM, et al. Closed vitreous surgery XVII.Results and complications of pars plana vitrectomy. Arch Ophthalmol. 1980;98:1248-1252. 4 Han DP, Lewis H, Lambrou FH Jr, et al. Mechanism of intraocular pressure elevation after pars plana vitrectomy. Ophthalmology. 1989;96:1357-1362. 5 Koreen L, Yoshida N, Escariao P, et al. Incidence of, risk factors for, and combined mechanism of late-onset open-angle glaucoma after vitrectomy. Retina. 2012;32:160–167. 6 Luk FO, Kwok AK, Lai TY, et al. Presence of crystalline lens as a protective factor for the late development of open angle glaucoma after vitrectomy. Retina. 2009;29:218–224. 7 Wu L, Berrocal MH, Rodriguez FJ, et al. Intraocular pressure elevation after uncomplicated pars plana vitrectomy: results of the Pan American Collaborative Retina Study Group. Retina. 2014;34:1985–1989. 8 Han DP, Lewis H, Lambrou FH Jr, et al. Mechanisms of intraocular pressure elevation after pars plana vitrectomy. Ophthalmology. 1989;96:1357. 9 Ichhpujani P, Jindal A, Katz JL. Silicone oil induced glaucoma: a review. Graefes Arch Clin Exp Ophthalmol. 2009;247(12):1585-1593. 10 Chang S. Intraocular gases. In: Ryan SJ, ed. Retina. vol. 3. St. Louis: CV Mosby, 1989:245. 11 Han DP, Lewis H, Lambrou FH, Mieler WF. Mechanisms of intraocular pressure elevation after pars plana vitrectomy. Ophthalmology. 1989;96:1357-1362. 12 Chen PP, Thompson JT. Risk factors for elevated intraocular pressure after the use of intraocular gases in vitreoretinal surgery. Ophthalmic Surg Lasers. 1997;28:37-42. 13 Mills MD, Devenyi RG, Lam WC, et al. An assessment of intraocular pressure rise in patients with gas-filled eyes during simulated air flight. Ophthalmology. 2001;108:40-44. 14 Cibis PA. Recent methods in the surgical treatment of retinal detachments: intravitreal procedures. Trans Ophthalmol Soc U K. 1965;85:111-127. 15 De Corral LR, Cohen SB, Peyman GH. Effect of intravitreal silicone oil on intraocular pressure. Ophthalmic Surgery. 1987;18:446-449. 16 Nguyen QH, Lloyd MA, Heuer DK, et al. Incidence and management of glaucoma after intravitreal silicone oil injection for complicated retinal detachments. Ophthalmology. 1992;99:1520-1526. 17 Honavar SG, Goyal M, Majji AB, et al. Glaucoma after pars plana vitrectomy and silicone oil injection for complicated retinal detachments. Ophthalmology. 1999;106:169-177. 18 Federman JL, Schubert HD. Complications associated with the use of silicone oil in 150 eyes after retina-vitreous surgery. Ophthalmology. 1988;95:870-876. 19 Haut J, Ullern M, Chermet M, Van Effenterre G. Complications of intraocular injections of silicone combined with vitrectomy. Ophthalmologica. 1980;180:29-35. 20 Watzke RC. Silicone retinopiesis for retinal detachment. A long-term clinical evaluation. Arch Ophthalmol. 1967;77:186-196. 21 Valone J, McCarthy M. Emulsified anterior chamber silicone oil and glaucoma. Ophthalmology. 1994;101:1908-1912. 22 Nguyen QH, Lloyd MA, Heuer DK, Baerveldt G, Minckler DS, Lean JS, Ligett PE. Incidence and management of glaucoma after intravitreal silicone oil injection for complicated retinal detachments. Ophthalmology. 1992;99:1520-1526. 23 Moisseiev J, Barak A, Manaim T, Triester G. Removal of silicone oil in the management of glaucoma in eyes with emulsified silicone. Retina. 1993;13:290-295. 24 Budenz DL, Taba KE, Feuer WJ, Eliezer R, Cousins S, Henderer J, Flynn HW. Surgical management of secondary glaucoma after pars plana vitrectomy and silicone oil injection for complex retinal detachment. Ophthalmology. 2001;108:1628-1632. 25 Ishida K, Ahmed I, Netland PA. Ahmed Glaucoma Valve surgical outcomes in eyes with and without silicone oil endotamponade. J Glaucoma. 2009;18:325-330. 26 Kim RW, Baumal CR. Anterior segment complications related to vitreous substitutes. Ophthalmol Clin North Am. 2004;17(4):569-576. 27 Han L, Cairns, JD, Campbell WG, et al. Use of silicone oil in the treatment of complicated retinal detachment: Results from 1981 to 1994. Aust N Z J Ophthalmol. 1998;26:299-304. 1
About the Contributing Doctor Dr. Sahebaan Sethi, MS, DNB, FICO, FMRF (Glaucoma) is currently working as a glaucoma specialist in Aronodaya Deseret Eye Hospital, an NGO non-profit organization in New Delhi, India. She has been trained at the prestigious Sankara Netralaya, Chennai, India, for glaucoma and phacoemulsification and completed her postgraduate course as a gold medalist. With years of experience in high volume charitable organizations, she has been actively involved in teaching and mentoring students. Having presented various national and international papers, she was honored with the “Developing Country Eye Researcher Fellowship Award” at ARVO 2004 Florida. She works as an ambassador of sight aimed to reverse the tide of curable blindness. Community service and research are her main areas of interest that she aspires to work towards. [email: firstname.lastname@example.org]
POSTERIOR SEGMENT SURGICAL COMPLICATIONS
Posterior Segment Complications of by Collins Santhanasamy
Posterior complications from cataract surgery can be difficult to untangle.
ataract surgery, despite being an anterior segment procedure, can sometimes cause posterior segment complications. Hence, the subject matter remains an important topic for expert discussion. At the recently held joint EURETINA-ESCRS 2018 Congress in Vienna, Austria, a diverse panel of vitreoretinal specialists connected with an enthusiastic crowd in a dynamic discussion of the posterior segment complications of cataract surgery. Based on presentation by Dr. Bhuvan Chanana, senior consultant, vitreoretina and uvea specialist, Bharti Eye Hospital and Foundation, India, on “Management of Dropped IOL and Nucleus” and “Endophthalmitis: Early Detection, Differentiation from Sterile Reaction and Management”.
anagement of intraocular lens (IOL) dislocation, according to Dr. Bhuvan Chanana, has been reported to occur in 0.2-1.8% of patients after cataract surgery. He stressed that the key to management of such complications is to remain calm and to avoid over manipulation in order to prevent extension of the capsular
tear and the development of further complications. Optimal times for intervention include intraoperatively and up to 2 weeks postoperatively when inflammation and corneal edema has subsided. Nuclear fragments less than 20% may not cause significant inflammation and may be reabsorbed spontaneously. The use of viscoelastics in the prevention of anterior migration of the vitreous and the use of sutures to keep incisions watertight to prevent postoperative complications such as hypotony or endophthalmitis are recommended. Attempts to follow the lens fragments by IOL fishing should not be pursued as these procedures
may lead to complications like retinal breaks, giant retinal tears (GRT) and even retinal detachment (RD). Surgical management like a 23-25G vitrectomy with removal of all vitreous adhesions around the lens fragments to avoid traction may be considered. Soft lens matter may be removed with cutter, but harder fragments are to be removed with a fragmatome. If handled correctly, a dropped nucleus or IOLs during cataract surgery in most cases do not lead to any serious complications if managed correctly during cataract operation and operated by VR specialist using pars plana vitrectomy and removal. Endophthalmitis, as discussed additionally by Dr. Chanana in the same symposium, is a common complication of cataract surgery. It is defined as an intraocular inflammation predominantly involving the vitreous cavity (leading to exudation in the vitreous cavity) and anterior chamber commonly as a result of intraocular colonization by microorganisms. In advanced cases, contiguous ocular structures such as the retina or choroid may be involved. It is very important to differentiate endophthalmitis from an exaggerated reaction as the management of such a case is very different, and a delay in the diagnosis may result in grave outcomes. An important prophylactic step recommended to decrease the incidence of postoperative endophthalmitis is 5% povidone iodine cleaning for at least three minutes. Single use instruments (including single use tubing) are always preferred. Data currently shows that there is no reduction in the risk of endophthalmitis with preoperative cutting of eye lashes and that taping back of the eyelashes instead in order to exclude them from the surgical field is recommended.
POSTERIOR SEGMENT SURGICAL COMPLICATIONS Based on presentation by Dr. Atchara Amphornphruet, Rajavithi Hospital in Rangsit University, Bangkok, Thailand, on “Cystoid Macular Edema: When and How to Treat?”.
seudophakic cystoid macular edema (PCME) is a common complication following cataract surgery,” noted Dr. Atchara Amphornphruet. It has a clinical incidence ranging as high as 2-12% in extracapsular cataract extraction (ECCE) and as low as 0.1-2.35% with the use of phacoemulsification. PCME remains an important cause of suboptimal postoperative vision. Although acute cases of PCME may spontaneously resolve without intervention within a span of 3-4 months, it may also progress to a chronic stage that affects vision. The incidence of PCME has however decreased over the years with the development of less invasive and traumatic cataract surgery techniques. Topical NSAIDs remain the mainstay in prevention and the management of PCME with topical, periocular and intraocular corticosteroids serving as a useful adjunct. Surgical intervention can be effective in certain cases and there is currently no standard algorithm for the prevention and treatment of PCME highlighting the need for more prospective randomized clinical trials.
Based on presentation by Dr. Heinrich Heimann, Royal Liverpool University Hospital, United Kingdom, on “Retinal Detachment in Mismanaged Cataract Surgery: Prevention, Etiology and Management”.
n standardized phacoemulsification surgery, the first year incidence of retinal detachment (RD) was relatively low at 0.16 – the 8-year cumulated incidence rose to 0.93 per eye. There was also a 4-fold increased risk when the fellow non-operated eye was used as a reference.
Posterior capsule (PC) rupture with myopia was found to be the most important risk factor while PC rupture was found to be the most important modifiable risk factor in pseudophakic retinal detachment (with vitreous loss being an important feature and increased difficulty with the presence of nuclear fragments in the vitreous). Dr. Heimann shared some tips with the audience on phacoemulsification. He stressed on the importance of having a good view of the operative field and mastering the slowest possible rhexis. Hydrodissection of the nucleus and complete separation of pieces decrease surgical complexity.
Based on presentation by Dr. Martin Zinkernagel, Department of Ophthalmology and Department of Clinical Research, Bern University Hospital, Switzerland, on “Inadvertent Globe Perforation during Local Anaesthesia for Cataract Surgery and its Management”.
rare yet devastating complication during peri- or retrobulbar block is globe perforation or penetration, which has an incidence of 1:16000 and 1:10000, respectively. Dr. Martin Zinkernagel highlighted that preventive strategies included the use of topical anaesthesia or a sub-tenon block, blunt needles and a technique which involves avoiding the globe by going transconjunctivally rather than through the skin. An early diagnosis followed by proper management is key to achieving the best possible outcome. Anaesthetic effects on the retina are usually reversible and an early vitrectomy for vitreous hemorrhage before retinal detachment develops is recommended.
Based on presentation by Dr. V. Chaikitmongkol, Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, on “Expulsive Hemorrhage: Early Detection and Management”.
xpulsive hemorrhage remains one of the most frightening complications that can occur during intraocular cataract surgery. It is an explosive accumulation of blood from the suprachoroidal space leading to an expulsion of intraocular contents and permanent vision loss. In order to decrease the risk of expulsive hemorrhage, sudden drops in intraocular pressure (IOP) should be avoided and the surgeon should always be alert for early signs of suprachoroidal hemorrhage. Extra precautions are necessary in patients at risk of coughing during surgery and or those who have underlying risk factors for expulsive hemorrhage. Dr. Chaikitmongkol emphasized that the key to preserving an eye in such a scenario would rely on early detection and prompt action. Primary surgical management would involve immediate closure of wound, creation of anterior pressure, IV medications and positioning of the patient in an extreme reverse Trendelenburg position to reduce central venous pressure. Primary drainage is controversial and is not recommended as it may be unsuccessful due to clotting of the hemorrhagic blood in the suprachoroidal space and may reverse the tamponade effect which would result in additional bleeding. Editor’s Note: PIE Magazine Issue 07 was distributed at the Joint EURETINAESCRS 2018 Congress, held in Vienna, Austria. Reporting for this story, “Posterior Segment Complications of Cataract Surgery”, also took place at EURETINA-ESCRS 2018.
POSTERIOR SEGMENT GENETICS AND DRUG DELIVERY
Gene and Drug Delivery for Retinal Diseases: What’s Out with antiquated delivery systems . . . and in with the new!
Based on a presentation by Dr. Rocio Herrero-Vanrell, Faculty of Pharmacy, Complutense University, Spain, called “Microparticles as Therapeutic Tools in Retinal Diseases”.
by Olawale Salami
ptimal drug delivery into the posterior segment remains an important challenge in the management of the many diseases affecting the retina. Current drug delivery options are largely limited to intravitreal injections, which can be associated with complications due to their invasive nature. Topical delivery can be inefficient, while systemic administration is not a viable option as large doses are needed to reach the necessary intraocular concentrations. Intraocular implants and gene therapy are additional alternatives. And until there is an optimal drug delivery system for posterior segment conditions, continued research and improvement is needed. Based on a presentation by Dr. Arto Urtti, University of Helsinki, Finland, called “Posterior Segment Pharmacokinetics: Connecting the Dots”.
ecently, Dr. Arto Urtti and colleagues from the University of Helsinki, Finland, provided a synopsis of posterior segment pharmacokinetics. Analyzing literature from studies in rabbits and humans, the authors showed that volume of distribution (Vd) was almost constant for all the compounds analyzed. For drug clearance following intravitreal dosing, Dr. Urtti explained that there is a very big variation, and this is highly dependent on the nature of compound studied. Proteins have much lower
clearance values (longer half-lives) and reduced inter-protein variability, as compared to small molecules which have higher clearance (up to 50 folds higher) owing to higher permeability through the blood-retinal barrier. Dr. Urtti explained the critical importance of other key pharmacokinetic parameters in vitreal drug disposition, such as drug binding to the vitreous, melanin binding and melanosome permeability. “Blood-retinal barrier permeability and melanin binding are the most important factors in posterior segment pharmacokinetics of small molecules,” concluded Dr. Urtti. He also added the for biologicals, diffusion in the vitreous and penetration to the retinal layers may also be important.
here is a therapeutic gap in delivering drugs to the posterior that needs to be addressed – and now, novel strategies to optimize retinal drug delivery are being developed. Dr. Rocio HerreroVanrell from the Faculty of Pharmacy, Complutense University, Spain, shared key insights into the state-of-the-art drug delivery options to the posterior segment. According to Dr. HerreroVanrell, available drug delivery options for posterior segment include nanoparticles (1-1000nM), microparticles (1-1000µm) implants (>1mm) and depot systems. “However, the right choice of appropriate drug delivery system depends on the target site, the ophthalmic disease and the anticipated duration of treatment,” he said. Microparticles have unique physicochemical properties which make them good options for posterior segment drug delivery. According to Dr. Herrero-Vanrell, microparticles can be administered as conventional injections, using conventional 30-32G needles. In addition, they are also useful for long term delivery and, depending on their size, they exhibit different drug delivery profiles. Furthermore, it is possible to include more than one active substance in the same formulation of microparticles, and they can indeed behave like an implant because they can aggregate at the site of administration. Dr. Herrero-Vanrell explained that microparticles exist either as microcapsules or microspheres and can be administered via the periocular, subconjunctival, subretinal and intravitreal routes. Several biodegradable polymers are available to prepare microparticles, however, polylactic glycolic acid (PLGA) is preferred because of its high biocompatibility.
POSTERIOR SEGMENT GENETICS AND DRUG DELIVERY In rats treated with spironolactone PLGA microspheres, sustained release of spironolactone has been shown, together with high intravitreal concentrations and excellent, dose dependent morphological and functional tolerance. “Biodegradable microspheres for intraocular drug delivery represent an alternative to repeated intraocular injections, no surgical procedures are needed and injections can be reformed through small gauge needles,” concluded Dr. Herrero-Vanrell. “They are able to release the drugs for several weeks or months, are able to encapsulate more than one drug and are therefore useful for multifactorial diseases, and can be used for personalized therapy,” he explained.
Based on a presentation by Dr. Einar Stefansson, University of Iceland, called “Cyclodextrin Nanoparticle Eye Drops for Retinal Diseases”.
t is well established that conventional eyedrops do not provide significant intra-retinal drug concentrations and are ineffective in retinal diseases. However, Dr. Einar Stefansson, from the University of Iceland, explained that for eye-drop based drug delivery, the molecule must not only be lipophilic to penetrate the eye wall, but must also be soluble in aqueous eye drop and tear film. Finding the optimal ocular drug delivery system means overcoming these limitations of conventional eye drops. According to Dr. Stefansson, these obstacles have been overcome using cyclodextrin nanoparticles. Cyclodextrin reversibly binds to lipophilic drug molecules making them soluble in water. These cyclodextrin-drug complexes aggregate to form nanoparticles of approximately 100nm in diameter, which adhere to the eye to provide sustained release. Dr. Stefansson noted that the drug molecules are gradually released into the tear film and then into the eye in a process that is reversible. Current published literature has shown that cyclodextrin nanoparticle eye drop suspensions increase solubility
of lipophilic drugs by 10- to 100-fold, compared to conventional eye drops. In addition, they allow extended duration of delivered drugs. Dr. Stefansson also discussed findings from a study that measured the concentration of dexamethasone in tear film after topical administration in rabbits and humans, using conventional versus nanoparticle-based delivery. The study showed sustained high dexamethasone concentrations with nanoparticles in both rabbits and humans. In addition, eye-tissue concentrations at two hours post-administration remained significantly higher with nanoparticles. These are supported by data from clinical trials in humans. “Contrary to what has been the dogma since the beginning of time, it is possible to deliver drugs to the retina with an eyedrop,” concluded Dr. Stefansson.
Based on a presentation by Dr. Ronald Buggage, Eyevensys SAS, Paris, France, called “Viral and Non-viral Gene Delivery for Retinal Diseases”. “The Eyevensys non-viral gene therapy ocular delivery platform overcomes the disadvantages of viral and non-viral vectors to offer a novel approach for the expression of therapeutic proteins in the back of the eye.”
ene therapy is one approach to deliver drugs to the retina. According to Dr. Ronald Buggage of Eyevensys SAS, Paris, France, gene therapy involves the transfer of therapeutic genetic material (DNA or RNA) via viral or non-viral vectors to correct or modify the expression of genes influencing a disease process. Gene therapy works either by replacing a disease-causing gene with a normal gene, inactivation of a diseasecausing gene by the introduced new gene, or as witnessed more recently through gene editing, by cutting out an abnormal gene – especially when the protein products of that gene are causing structural defects.
Dr. Buggage says the eye is an ideal target for gene therapy for several reasons. Firstly, the globe is enclosed and relatively separate from the rest of the body and is an immune privileged space. In addition, retinal cells do not divide, therefore genes delivered have high chances of long-term expression. Furthermore, the small size of the retina means that small doses of vectors are needed, and outcomes can be easily monitored non-invasively. Another important reason is that the genetics of many inherited retinal diseases are well described, and suitable animal models are available. Dr. Buggage also highlighted that ocular gene therapy is not only for inherited retinal diseases: Current data shows that age-related macular degeneration (AMD) remains the number one indication for ocular gene therapy. Viral vectors are the most commonly used vectors and, as noted by Dr. Buggage, “will likely remain the preferred gene therapy vector for inherited retinal diseases, with future generations of engineered viral vectors expected to show fewer safety concerns”. “Non-viral vectors are a promising tool for sustained ocular drug delivery that may facilitate the development of new treatments for the posterior segment. The Eyevensys non-viral gene therapy ocular delivery platform overcomes the disadvantage of viral and non-viral vectors to offer a novel approach for the expression of therapeutic proteins in the back of the eye,” concluded Dr. Buggage. “The EYS606 [an Eyevensys lead product], being evaluated for the treatment of non-infectious uveitis will further clarify the risks and potential benefits of electro-transfer for non-viral gene delivery platforms.” Editor’s Note: PIE Magazine Issue 07 was distributed at the Joint EURETINAESCRS 2018 Congress, held in Vienna, Austria. Reporting for this story, “Gene and Drug Delivery for Retinal Diseases: What is Next?”, also took place at EURETINA-ESCRS 2018.
POSTERIOR SEGMENT VITREORETINAL SURGERY
Alcon’s NGENUITY Revolutionizes Surgery with
Greater Depth and Visualization
hanks to Alcon, the global leader in eye care, ophthalmic surgeons now have a new tool that will revolutionize the way they operate: Introducing the NGENUITY 3D Visualization System with DATAFUSION. The NGENUITY system’s high definition screen provides retinal surgeons unprecedented 3-D visualization of the back of the eye, with greater depth and detail during surgery than with traditional microscopes. Plus, with the DATAFUSION software, NGENUITY is now combined with the CONSTELLATION Vision System – the leading technology platform for vitreoretinal surgery. All of these revolutionary systems are linked together, which allows surgeons to track real-time data feedback on one screen during procedures. In addition, when compared with traditional analog microscopes, NGENUITY delivers up to 19 percent increased magnification, up to 2.7 times extended depth of field, and up to 19 percent increased depth resolution. These increases are much-needed by surgeons to see finer details during intricate surgeries. “The high magnification is a real boon and a great advantage because you can look at the peripheral retina and look for tiny breaks which are often missed in the preoperative examination,” said Dr. Atul Kumar, a CONSTELLATION and NGENUITY user. The extended depth of field also helps surgeons like Dr. Kumar know how far away the membrane is from the retina. In the past, Dr. Kumar says it was difficult to operate using traditional visualization – without 3-D visualization he couldn’t get the magnification he wanted: “I couldn’t see those semivisible membranes or nearly invisible membranes on the retinal surface as well as I see them now,” he explained. And for many surgeons, when you can see better, you can treat better.
The high magnification is a real boon and a great advantage because you can look at the peripheral retina and look for tiny breaks which are often missed in the preoperative examination. Dr. Atul Kumar
“I can treat a pathology much better intraoperatively, and the results seem to be much better using NGENUITY,” Dr. Kumar added. In addition, the high magnification is useful for many surgeries, including diabetic vitreous surgery. This is a benefit to Dr. Kumar as advanced diabetic eye diseases are common in India due to the high number of diabetic patients. Dr. Kumar also says that the system has a short learning curve: “I picked it up very quickly… it took two weeks, and then I wanted to purchase the machine. We got the first unit in India,” shared Dr. Kumar. The system is also beneficial for his students and residents as they can see exactly what he is doing on the big screen. “Before the advent of NGENUITY, we used to just look at the tiny screen on the wall. That was a big handicap. Now we have a huge screen and they get to see what I’m doing. It is a very useful educational device. The younger generation will really benefit from NGENUITY,” said Dr. Kumar. One of the other surprising benefits of NGENUITY for surgeons is that it’s a pleasure to use – many surgeons feel almost like they are watching a movie from the comfort of their own home. “It is making me enjoy my surgery, otherwise it can become drab and boring … you don’t move forward,” he added. “I love watching the screen
now. I can’t go back to looking through the microscope. I feel that without the screen, I will be handicapped.” The DATAFUSION software seamlessly integrates the CONSTELLATION Vision System and the NGENUITY 3D Visualization System, allowing surgeons to track key data parameters on one screen in real-time, such as intraocular pressure, flow rates, infusion pressure and laser power. Dr. Atul Kumar is one of the many surgeons in India excitedly looking forward to the DATAFUSION software upgrade in their existing systems. “I can alter my parameters accordingly based on the surgery and what is happening. It is going to be more helpful for the surgeon,” said Dr Kumar. He says surgeons will not want to go back to analog after trying NGENUITY: “Even if I leave this hospital and go into private practice I will still need NGENUITY. Now, I don’t want to operate without it,” he said. Dr. Atul Kumar is chief and professor of ophthalmology at the Dr. Rajendra Prasad Center for Ophthalmic Sciences (RPC-AIIMS), the National Apex Ophthalmic Centre at All India Institute of Medical Sciences, Delhi. He also heads the Vitreo-Retinal, Uvea and ROP services at RPC-AIIMS.
POSTERIOR SEGMENT VITREORETINAL SURGERY
Revelations in by Olawale Salami Based on presentation by Dr. Armin Wolf, Ludwig-Maximilians-University of Munich (LMU) Eye Clinic, Munich, Germany, on “Combined Phacovitrectomy: Killing 2 birds with One Stone”.
cenarios where patients present with dual pathologies, like cataract and posterior segment disease, are not uncommon. Dr. Armin Wolf, LudwigMaximilians-University of Munich (LMU) Eye Clinic, Munich, Germany, shared insights into surgical options when managing patients presenting with these cataract and posterior segment pathologies. Available options, Dr. Wolf noted, are a sequential surgery (i.e. cataract surgery and subsequent vitrectomy or vice versa), or a one-step combination of cataract surgery and vitrectomy (i.e. phaco-vitrectomy). While discussing disadvantages of combined phaco-vitrectomy, Dr. Wolf noted that there is sufficient data showing postoperative inflammation, especially in young diabetic patients. However, these data, he cautioned, are from studies conducted over 20 years ago and surgical techniques have evolved remarkably since then.
Additional consideration should be given to possible higher risks of biometric and IOL errors following combined phaco-vitrectomy as compared to a sequential approach. So why should phaco-vitrectomy be the preferred option? One argument, according to Dr. Wolf, is that vitrectomyinduced cataract is almost inevitable with age, therefore a combined approach solves this beforehand. In addition, Dr. Wolf said: “Increased patient costs of two or more different surgeries and logistic challenges of referral from and a cataract to a retinal surgeon are important reasons why a combined approach could be more patient friendly.” Furthermore, a combined procedure allows for optimal anterior vitreous resection during vitrectomy, which might be difficult during vitrectomy alone. Published studies discussed by Dr. Wolf showed that, compared with sequential surgery, phaco-vitrectomy showed no differences in both clinical outcomes and in surgical success rates. The advent of modern imaging techniques has had profound influence on combined phaco-vitrectomy allowing better evaluation of biometric and functional results.
Considering available literature, Dr. Wolf noted that “the predictive error of combined vitrectomy remains high”. In addition, Dr. Wolf emphasized: “ERM detection is vital towards the surgical planning given its association with a higher risk of axial length measurement errors and possible higher risk of central macular edema in cataract surgery.” Furthermore, he added that sequential surgery may still be an option, but it’s important to note that up to 20% of those patients may not require vitrectomy after cataract surgery. “Therefore, individual evaluation of each patient is key in deciding between a combined and sequential approach,” he concluded.
Based on presentation by Dr. Andreas Stahl, Eye Centre, University of Freiburg, Germany, on “Intraoperative OCT Remains Useful in VR Surgery”.
The iOCT is very useful in situations where we need to visualize a pathology while manipulating it, and not just before or after surgery.
Hmm...nah. Better to “kill two birds with one stone” with combined phaco-vitrectomy instead.
ll vitreoretinal (VR) surgeons dream of the ideal intraoperative optical coherence tomography (iOCT) device. A device that is intuitive, with errorfree handling, that can help improve intraoperative safety and surgical outcomes and more importantly, gain insights into pathology and shorten surgery time. Do the current iOCT devices meet these criteria? Dr. Andreas Stahl of the University of Freiburg, Germany, evaluated the utility of iOCT in VR
etinal Surgery surgery. “In everyday settings, in my opinion, in routine epiretinal membrane peeling, there is little advantage with the use of iOCT,” said Dr. Stahl. However, Dr. Stahl noted that there are special situations where the iOCT is very helpful in visualizing pathologies that underlie the clinical picture. These include macular detachment from optic pit disc, vitreal traction. “Therefore, the iOCT is very useful in situations where we need to visualize a pathology while manipulating it, and not just before or after surgery,” he said. Dr. Stahl concluded that: “iOCT is intuitive, although it takes time to learn. It can improve intraoperative safety in selected situations. It certainly helps to gain novel insights into pathologies, but it does not necessarily lead to shorter surgery times as it needs time to set-up.”
Based on presentation by Dr. Heinrich Heimann, Royal Liverpool University Hospital, United Kingdom, on “Retinal Detachment: Who Needs a Buckle Anyway?”.
r. Heinrich Heimann of the Royal Liverpool University Hospital, United Kingdom, traced the evolution of retinal detachment surgery from the era of pre-buckling technique in the 1920s to the 1950s, through scleral buckling in the 60s, 80s and 90s, and to standard vitrectomy today. Today, very few surgeons are performing scleral buckling. Data from clinical studies have consistently shown superior anatomical success rates with vitrectomy. However, there is emerging data that points towards increased frequency of postoperative adverse events, and poorer visual outcomes with vitrectomy as compared to buckling. According to Dr. Heimann, there is of late, a lot of renewed interest in scleral buckling among surgeons. He noted that in an analysis of 7000 retinal
detachments surgeries performed by consultants and trainees in the United Kingdom, experts observed no difference in vitrectomy failure rates among the two groups. “However, we have seen higher rates of surgical failures of scleral buckling in trainees as compared to consultants. This means we can use this data as an argument that we need more training,” Dr. Heimann said. Furthermore, Dr. Heimann shared success stories from the training program for vitreoretinal surgeons in Liverpool, where scleral buckling training has been reinforced. However, he noted that, compared to primary vitrectomy, scleral buckling is more difficult to teach and learn, and the anatomical result does not always appear better. “It is known that primary vitrectomy is associated with acceptable results and the surgery is much easier. So why choose scleral buckling?” asked Dr. Heimann. To which he responded with: “If you want the best results, then you should continue to buckle. In addition, it is associated with better overall outcomes in certain situations such as in pediatric cases, and fewer secondary surgeries.”
Based on presentation by Dr. Nicolas Feltgen, University of Goettingen, Germany, on “Dead-ends in Vitreoretinal Surgery: Learning from the Past”.
oday we see many failures published in the literature by retinologists, where conclusions are made because certain procedures or techniques have reached dead-ends and no longer work. But what is a deadend and how can surgeons recognize this? Are there historical examples that can help us recognize when we have reached a dead-end? Dr. Nicolas Feltgen, from the University of Goettingen in Germany,
demonstrated how dead-ends are reached and can be avoided, using interesting historical clinical cases. Dr. Feltgen narrated that in retinal vein occlusion, many surgical procedures have been tried in the past. Endovascular thrombolysis, first introduced in 1998, was thought to be associated with remarkable patient results and few complications, based on published data. However, these results could not be replicated in many patients and a lot of complications were recorded. However, data published 20 years ago had shown that cell proliferation and thrombus organization occurred within a few days, so early vitrectomy within two weeks is indicated. Are collaterals good for the retina? Despite early data from radical optic neurotomy and chorio-retinal anastomoses showing improvements in patient outcomes, Dr. Feltgen noted: “Today, we know that collaterals correlate with ischemia and do not improve vision.” In patients with diabetic macular edema, early data from the 1990s had shown interesting outcomes following removal of sub-retinal exudates. However, a review of the data from these studies revealed questionable study designs, and similar outcomes were not seen in other patient cohorts. Today, we also know that retinal tacks for Coats’ diseases are too traumatic. “These lessons from the past have been useful today, because retinal surgeons are brave, curious and do not hesitate to admit failure,” concluded Dr. Feltgen. Editor’s Note: PIE Magazine Issue 07 was distributed at the Joint EURETINA-ESCRS 2018 Congress, held in Vienna, Austria. Reporting for this story, “Revelations in Vitreoretinal Surgery?” also took place at EURETINA-ESCRS 2018.
POSTERIOR SEGMENT ANTI-VEGF AGENT
Aflibercept Receives Approval for
Proactive Treat-and-Extend Regimen
by Brooke Herron
ayer (Leverkusen, Germany) announced the big news during its lunch symposium at the 18th EURETINA Congress on September 21: As of July 20, 2018, aflibercept (EYLEA) has been approved in Europe and elsewhere for use with a proactive treatand-extend (T&E) regimen starting in the first year of treatment in neovascular age-related macular degeneration (nAMD). This new posology allows for an extension of treatment in two- or four-weekly increments in year one at the discretion of the physician. Currently, a variety of treatment regimens are used in clinical practice for treatment of nAMD. These include the reactive PRN and treat-to-target and the proactive fixed dosing and T&E. During the symposium, Drs. Peter Kaiser (USA), Gemmy Cheung (Singapore) and Paul Mitchell (Australia) discussed aflibercept in terms of a T&E regimen. In T&E, patients are injected at scheduled visits, regardless of visual acuity (VA) or anatomic status – treatment is initiated with loading doses until the disease is stable. Then, from there, treatment intervals are extended until sub-retinal fluid recurs or visual acuity (VA) declines. Multiple studies have shown that aflibercept is effective in a proactive T&E regimen. In the VIEW study, the mean number of injections patients received in year one was 7.5 and in year two, this was reduced to 4.2. Not only was
there a reduction in injections, 48% of patients who received aflibercept 2q8 in year one maintained VA gains in year two, with injection intervals of 12 weeks – and the VIEW 1 extension shows that those vision gains were maintained for more than four years with continued proactive aflibercept treatment. The PLANET study produced similar results. Patients with PCV received q8 aflibercept and mean injections from year one to two dropped from 8.1 to 4.6, respectively. Plus, they gained >10 letters and maintained VA gains to week 96 with optional T&E. This data shows that good visual outcomes can be achieved with a proactive aflibercept regimen in realworld clinical practice. “Other studies have used this idea of starting q8 week fixed dosing after a loading dose and switching to treat and extend after one year,” said Dr. Kaiser. He notes that in the PLANET study, VA results were great and polyp regression rates were also excellent. “The important thing to note, is that in that second year of the study they switched to treat-and-extend and there was a dramatic reduction in the need for injections while maintaining visual acuity gains – and that’s really what we want for our patients,” he said. The VIEW and PLANET studies are joined by mounting evidence from additional real-world studies of proactive q8 and T&E aflibercept dosing.
“Studies from all over the world are showing similar visual acuity results between the real-world studies and the randomized clinical studies of VIEW and PLANET,” said Dr. Kaiser, Professor of Ophthalmology, Cleveland Clinic College of Medicine, Cleveland, Ohio, USA. “But we’re also seeing real world studies using treat-and-extend, which is something we’re seeing more and more worldwide. And results in these real-world studies, using treat-and-extend is similar again to the to the studies using fixed dosing in terms of VIEW and ALTAIR.” In 2016, Epstein et al. published a retrospective study of 85 patients with nAMD who received intravitreal q8 aflibercept to month 12, followed by a proactive T&E regimen to month 18. They found that VA gains achieved with q8 aflibercept in year one (7.7 mean number of injections in months 0-12) were maintained to with proactive T&E to month 18 (2.2 mean injections from months 12-18). Other studies (Eleftheriadou et al. 2018; Hosokawa et al. 2018) found similar results: VA was maintained and the number of injections was reduced. Other than less injections and better visual acuity (VA), this treatment method offers additional benefits to both patients and caregivers. In a 2017 study, Hanemoto et al. found that a proactive T&E regimen was associated with a reduced burden on patients and caregivers compared with PRN, reducing the mean number of visits in one year to 7.9 (T&E) from 14.0 (PRN).
The ALTAIR Study ALTAIR is a Phase IV study designed to evaluate the efficacy of aflibercept with two different T&E dosing regimens in patients with nAMD. The primary objective was to assess the efficacy of aflibercept with two different treatment regimens in nAMD over two years. The secondary objective assessed the safety. This was a multi-center, randomized open-label study in treatment-naïve patients with nAMD (≥50 years old;
BCVA of 25-73 ETDRS letters [~20/40 to 20/320] in the study eye). All patients received aflibercept treatment (3 x q4) and were randomized (1:1) at week 16 to either receive a 2-week interval adjustment (n=124) or 4-week (n=123). At week 52 (the primary endpoint) there was a mandatory visit to note changes in best corrected visual acuity (BCVA) from baseline. At week 96, the endpoint was studied. Adjustment of T&E treatment intervals was guided by specific criteria. Intervals were extended if there was no sub-retinal fluid and no loss of ≥5 ETDRS letters, no increase of CRT of ≥100 µm, no new neovascularization and no new macular hemorrhage. Intervals were shortened if new fluid was present, or there was persistent unchanged or increased fluid, along with any of the following: loss of ≥5 ETDRS letters, increase in CRT of ≥100 µm, new neovascularization or new macular hemorrhage. Intervals were maintained if there was residual but decreased sub-retinal fluid, along with the same criteria of the extended treatment regimen. From weeks 16 to 96, the minimum interval was 8 weeks, while the maximum interval was 16 weeks.
At the primary endpoint (52 weeks) rapid vision gains were achieved in both treatment groups, and mean injections were similar (7.2 in 2-week group and 6.9 in 4-week group). These vision gains were maintained until week 96, while the number of injections continued to drop (3.6 in 2-week group and 3.7 in 4-week group). Around 30% of patients gained ≥15 ETDRS (3 lines of vision) in both treatment groups at week 52 and week 96. Fifty-seven to 60% of patients were maintained with injection intervals of 12 weeks or beyond at week 96. “Over 40% percent of patients, those who do very, very well reach the maximum retreatment level of 16 weeks,” said Dr. Cheung. “Data from ALTAIR underlines the efficacy of proactive T&E with aflibercept over two years of treatment in patients with nAMD. It has demonstrated considerable visual gains at the end of the first year, which is well maintained at the end of the second year, at the same time with a significant reduction in the number of injections, particularly seen in the second year.” In addition, the safety profile of intravitreal aflibercept in ALTAIR is consistent with results in previous studies.
The ARIES Study
Dr. Gemmy Cheung
“We have experienced that there is a proportion of eyes that just cannot dry up completely, but their vision is stable, they don’t have new fluid, or new hemorrhage,” said Dr. Gemmy Cheung, Senior Consultant Ophthalmologist at the Singapore National Eye Centre (SNEC) and a Clinician Investigator at the Singapore Eye Research Institute (SERI). “There might be a bit of residual fluid, but this is actually decreasing and vision is stable, there are no other signs of activity.”
ARIES is a Phase IIIb/IV study designed to investigate the efficacy of aflibercept with early (initiated after the first 8-week treatment interval) versus late initiation (at year one) of a T&E dosing regimen in patients with nAMD. This was a multi-center, openlabel, active-controlled, parallel group, Phase V study in treatment-naïve patients with nAMD. Patients were randomized at week 16 into either “early start” aflibercept 2mg with a twoweek interval extension, or “late start” aflibercept 2mg q8 regimen. At 52 weeks, a mandatory visit was required and the late start group began a twoweek interval extension. The study found that rapid vision gains were maintained to week 52 and were similar in both groups. The
Prof. Paul Mitchell
mean change in BCVA from baseline to week 52 was +6.8 letters in the early start group and +8.4 in the late start group. These results were parallel and the difference in BCVA was attributed to baseline characteristics rather than the treatment regimen. Professor Paul Mitchell, University of Sydney, Australia, notes that any changes in CRT were also due to differences in baseline characteristics. Additionally, around 98% of patients maintained vision from baseline in ARIES, which is consistent with aflibercept-treated patients in the VIEW trials. “In summary, preliminary data from ARIES corroborates existing evidence supporting the suitability of aflibercept for early proactive treat and extend regimen, with 52-week analysis the visual and anatomic outcomes were similar in patients in both early start and late start,” concluded Prof. Mitchell. Overall, the dual mechanism of action and high binding affinity of aflibercept, and its sustained suppression of intraocular VEGF, make it suitable for a proactive T&E dosing regimen in nAMD. In addition, in clinical practice, proactive T&E dosing with aflibercept starting in year one is associated with rapid vision gains that are maintained thereafter with a reduced treatment burden. Editor’s Note: A version of this article first appeared in PIE Post Day 2 issue published at EURETINA 2018 Congress in Vienna, Austria (page 6-7, 10). PIE Post is PIE Magazine’s Daily Congress News on the Posterior Segment.
Transforming Information into Insight with
Integrated Diagnostic Imaging
ime is of the essence – especially when managing progressive disease and prescribing treatment for sight threatening conditions that require swift and accurate intervention. In a busy practice, where multiple diagnostic innovations are at play, a myriad of important but overwhelming testing data are being generated for each case. The arduous process of finding correlations among all the results is challenging for physicians who prefer to spend less time interpreting and more time leading their patients to better outcomes. For Dr. Peter A. Karth, M.D., a Retina and Vitreous Physician & Surgeon, board certified ophthalmologist and fellowship trained retina specialist in Oregon (USA), reviewing and analyzing this everincreasing amount of data has become increasingly complex and unbearably time-consuming. “I need to be able to use this mountain of diagnostic data to support complex, and often expensive, treatment decisions,” he says. This task takes time – and as patient loads increase, it must be done quickly. “How can we leverage our diagnostic tools to provide more efficient care to our patients? For me, the answer is simple: improved data integration, visualization, and analysis,” says Dr. Karth. Thankfully for Dr. Karth – and ophthalmologists worldwide – an answer has arrived. From Carl Zeiss Meditec Inc. (Jena, Germany), the Integrated Diagnostic Imaging (IDI) platform not only means better care for patients, but more efficiency for doctors as well. This powerful software-driven system allows doctors to visualize and analyze data from different modalities all on one screen.
IDI Glaucoma case
Recently unveiled at the European Society of Cataract and Refractive Surgeons (ESCRS) 2018 meeting in Vienna, Austria, the ZEISS Integrated Diagnostic Imaging easily and seamlessly pieces together images from multiple modalities over time. By gathering, integrating and combining data from different diagnostic devices and developing simple individualized assessments, this platform helps doctors make optimal treatment decisions, quickly and efficiently.
IDI BRVO case
IDI is expanding physicians’ level of care by providing a clinical cockpit for understanding. With multi-modal and treatment effect overlays, pointto-point registration and expanded temporal comparison ability, IDI is changing the landscape of diagnosis and treatment… for the better. This multi-modality in diagnostics and imaging is increasingly becoming the standard of care in eye clinics. Not only does this technology save precious time, the ability to assess and compare
IDI 2Up screens
IDI is expanding physicians’ level of care by providing a clinical cockpit for understanding. With multi-modal and treatment effect overlays, point-to-point registration and expanded temporal comparison ability, IDI is changing the landscape of diagnosis and treatment… for the better. data from multiple modalities also gives doctors more confidence in proposing customized treatment regimens for each patient’s needs. This could have an impact on diagnosis and treatment of complicated retinal conditions. According to Dr. Karth, this integration is crucial in detecting, diagnosing and treating retinal disease. “One of the biggest challenges in retina practices today is viewing and integrating multimodal imaging to efficiently and fully assess macular disease in busy clinics,” says Dr. Karth. For retinal applications, the IDI works with ZEISS’s gold-standard instruments such as CIRRUS™ HDOCT, ultra-widefield retinal camera CLARUS® 500, complimented with therapy with the new VISULAS green therapeutic laser.1 It allows physicians to see all relevant imaging on one screen, navigate patient data up to
three visits at a time, track treatment efficiency with history charts and clinical events, and review and analyze multiple exams simultaneously. In addition, data from OCT Angiography can be registered from CIRRUS AngioPlex, and AngioPlex Metrix quantification tools support complex disease investigation. In addition, True Color HD ultra-widefield fundus images can be integrated and registered with OCT Angiography for targeted pathway visualization . . . allowing doctors to fully assess retinal diseases from the macula to the periphery in seconds. “Retinal workplace2 gives clinicians fully integrated multi-modality assessment capabilities from the macula to the periphery with a single click in a few seconds all-in-one view,” adds Dr. Karth. The ability to integrate data from multiple modalities is not just beneficial
for detecting and treating retinal diseases, it’s also valuable for managing glaucoma, a complex progressive disease that requires continuous followup assessment. In glaucoma, with the IDI, results from visual field testing and OCT can be combined and associated to enable clinicians to identify changes in progression that could impact disease management. It simplifies the complex with a unique combination of data from the Humphrey Field Analyzer and CIRRUS OCT. By viewing this integrated information, doctors can detect signs and symptoms of glaucoma early, identify changes and create an individualized treatment plan. These digital solutions can help doctors who are faced with an overwhelming amount of data from different sources – making eye care even more complex. Not only is analyzing this data time-consuming, it can also be inefficient: If the data is not correctly identified in the clinical findings, doctors could miss something that is vital to their treatment and prognosis. ZEISS and IDI are working to change that by transforming data into turning points of care. “I consider the ZEISS Integrated Diagnostic Imaging platform to be a key part of patient management, giving me the data integration that I need to make the best decisions for my patients,” adds Dr. Karth. For more information about IDI and to watch related videos, visit: https://www.zeiss.com/meditec/int/c/ zeiss-integrated-diagnostic-imaging. html. This content was supported by an educational grant from Carl Zeiss Meditec. The products mentioned in this article may not be available in all regions for all indications.
VISULAS green therapeutic laser is 510(k) pending. 2 RETINA Workplace 2.5 is 510(k) pending. 1
The Golden Rules of
by Brooke Herron
old – it’s a metal so precious that it has been used to guarantee the value of currencies worldwide. In addition to its monetary worth, this prized natural resource is often interjected into common phrases like “the gold standard,” where it’s used as a benchmark to describe something of the highest quality. In the medical field, the “gold standard” of patient care and treatment is constantly evolving with the advent of new technologies and therapies. Additionally, the gold standard can differ from country to country, or even within a country. In India, a large and diverse subcontinent, it can be often
based on availability of resources, access to care and cost. A 2018 review article published in the Indian Journal of Ophthalmology1 observed that eye care in India is at a crossroads – between adherence to the older, successful models and adoption of newer innovations and methods. The authors believe that “in the absence of these new approaches, the initial gains in eye care could not be furthered in India”. In this type of landscape, the benchmark – or gold standard – is fluid. In this cover story, we speak with three Indian vitreoretinal surgeons to explore their views on what is “gold,” and discuss what is needed to raise that benchmark even higher.
Setting the Gold Standard for Diabetic Retinopathy A 2017 study published in the Journal of Ophthalmology stated that diabetic retinopathy (DR) is the most frequent microvascular complication and its prevalence increases with the duration of diabetes. Meanwhile, the authors revealed that diabetic macular edema (DME), which is the main cause of blindness in working-age adults in industrialized countries, occurs in 7.5% of diabetic patients.2 According to vitreoretinal surgeon Dr. Pushkar Dhir, because India is one of the world’s fastest growing economies, the country shares the burden of being the diabetic capital
The nitty gritty of treating diabetic retinopathy is endless . . . from intravitreal injections to lasers . . . but these are all adjuncts. The ‘gold’ in ‘golden rule’ is your body – when there’s less fat, the more effectively insulin can work. – Dr. Pushkar Dhir
Dr. Abhishek Kothari, a consultant vitreoretinal surgeon in Jaipur, India, agrees that one of the most prevalent conditions in India is DR and its complications. He says: “The high prevalence of diabetes, especially in the urban population where I practice, and the low awareness among patients leads to more advanced stages of disease at presentation.” “Ophthalmology fascinates me . . . [to think] that approximately the 1,100 square mm of area in the eye – which is the door to our mind and body – and the retina can develop so many pathologies,” added Dr. Pushkar. “And just one of these pathologies can just close that door forever. So, it’s important to find out and treat it at the earliest [stage].”
of the world (along with China and the United States). “The figures don’t make me proud . . . but we share approximately 49 percent of the world’s diabetes burden, with an estimated 72 million cases in 2017 – thus, making DR one of the most prevalent condition in India,” he said. In 2014, the All India Ophthalmological Society (AIOS) presented results from its Diabetic Retinopathy Eye Screening Study. The authors estimate that by 2030, 79.4 million Indians will be affected by diabetes mellitus, and the majority of those are expected to develop diabetic retinopathy over time.3
‘Gold’ Begins with the Patient With so many in the crosshairs of this debilitating disease – and with levels of health literacy and access to care varying widely – educating patients becomes the first step in preventative care. This includes tight metabolic control, control of risk factors, and close monitoring of progression of preexisting DR – as these are indispensable measures to prevent vision loss.2 Physical exercise is also a major proponent of preventing the advance of DR. “I might sound like a philosopher, but these Latin words hold true: ‘menssana in corpore sano’, meaning ‘a sound body has a sound mind’,” said Dr. Pushkar.
Dr. Pushkar sees more than 100 posterior segment patients per day. As a younger doctor in his 30s, he says that this has made him realize that the time to act, to make exercise part of an everyday routine, is now. “You cannot mess up your body – if you ignore your body, then get ready to embrace an uncheerful old age,” he continued. “If you are over 25-yearsold, make sure physical activity is part of your routine.”Dr. Pushkar says the best activity that can be done with zero investment is running (or walking). For Dr. Kothari, the gold standard of treating DR also begins with the patient. To improve compliance, he counsels about the chronic nature of the disease and provides instructions for continued treatment and/or monitoring – this also includes good systemic control of DM. Another patient-focused goal is to reduce the cost and treatment burden, thus improving quality of life. “The nitty gritty of treating diabetic retinopathy is endless . . . from intravitreal injections to lasers . . . but these are all adjuncts,” added Dr. Pushkar. “The ‘gold’ in ‘golden rule’ is your body – when there’s less fat, the more effectively insulin can work.”
Raising the (Gold) Bar in DR Treatment Currently, Dr. Kothari treats proliferative diabetic retinopathy (PDR) with laser or surgery as required, while DME is treated with injections of anti-VEGF and
While there are gold standard treatments for DR, the burden of undertreatment for DME is huge. Any innovation that addresses compliance and cost of treatment has the potential to become the gold standard in its management.
– Dr. Abhishek Kothari
steroids, and lasers. “These treatments are effective and have the potential to preserve and improve vision in the vast majority of patients,” he said. Generally, treatment with laser photocoagulation is used to treat two key complications: retinal neovascularization and severe or clinically significant macular edema. In addition, early panretinal photocoagulation should be considered in those patients at a higher risk of progression, including patients with long-standing diabetes and poor metabolic control, presence of hypertension or advanced renal disease, non-compliance with scheduled visits, PDR in the fellow eye, among other risk factors.2 Studies have also shown that intravitreal therapies with anti-VEGF agents (like aflibercept, ranibizumab, and bevacizumab), have substantially
improved the prognosis of potentially severe ocular diseases, including DME. It’s been noted that aflibercept is probably the most cost-effective option because it requires fewer injections, thus reducing workload in a daily practice.2 And while there are gold standard treatments for DR, according to Dr. Kothari, the burden of undertreatment for DME is huge. “Any innovation that addresses compliance and cost of treatment has the potential to become the gold standard in its management,” said Dr. Kothari. New molecules in the pipeline could improve treatment for DR and its related conditions, like brolucizumab (Novartis; Basel, Switzerland) and abicipar (Allergan; Dublin, Ireland). “One of the major advantages of the newer molecules would be their longer duration of action, leading to less frequent dosing and improved patient compliance,” explained Dr. Kothari. “A port delivery system for ranibizumab, which requires a short procedure but has lasting effects, is also undergoing trials and may prove very useful for DME patients.” He says it’s heartening to see several such innovations on the horizon – some in phase II and other completing phase III trials: “These developments will improve the quality of care for patients with DME.” Dr. Pushkar finds new imaging tools critical to assisting with this task. “OPTOS is fantastic,” he said. “One click, and imagine you can scan the whole (200 degrees) of the retina and choroid, leaving very little scope and details missed.” He says in this everincreasing diabetic world, this machine could be a game changer in screening and early management. Another innovation set to change the game is artificial intelligence (AI). “There is this new concept which will change the ophthalmic world, from learning to treatment, from doctor diagnosis to a patient coming in with a diagnosis,” said Dr. Pushkar. “There
are already applications in the market where you upload scans and get the results. The more revolutionary ones pick up diabetic retinopathy patients, and then with one push of a button, they [the machine] do the lasers too. It is going to be a fascinating future.”
Setting the Gold Standard for Retinal Detachment Dr. Atul Kumar, chief and professor of ophthalmology at the All India Institute of Medical Sciences AIIMS) in New Delhi, India, says the most common surgical condition in India is rhegmatogenous retinal detachment (RRD), which is closely followed by diabetic traction RD (D-TRD) – a complication of DR. Research published in the National Medical Journal of India (2015) agrees that RD is the most common indication for retinal surgery in India4, with risk factors including myopia, previous cataract surgery and gender. Worldwide, the annual risk of RD is between 6.3 and 17.9 per 100,000.5 The two most important factors in the development of RRD are retinal breaks and vitreous traction.6 To avoid a profound loss of vision, treating RRD involves prompt – and major – surgery to close the retinal breaks and relieve all vitreous traction. “I treat such retinal detachments with a primary vitrectomy procedure or alternatively, a bucklevitrectomy principle,” said Dr. Kumar. He says this treatment depends on the location of the breaks and if proliferative vitreoretinopathy (PVR) is present. The two most commonly utilized techniques for repair of an RRD are scleral buckling and PPV – although there is still no consensus in the vitreoretinal community regarding the primary management of RRD.6 Pars plana vitrectomy (PPV) is often used because it allows for direct relief of vitreous traction associated with retinal breaks. In a paper published in 2018, the authors stated that PPV patients generally tolerate the surgery
For intraoperative viewing, NGENUITY 3D Visualization System is the gold standard. . . It helps me obtain higher magnification for viewing as I sit straight and watch the large screen displaying the surgery – Dr. Atul Kumar well (with regard to pain level) and single operation success rates for PPV have been reported to be in the range of 85 to 90 percent. Combined PPV and scleral buckling surgeries showed a trend toward a greater anatomic success rate in pseudophakic patients.6 In the buckle-vitrectomy combined surgery, Dr. Kumar places a belt buckle around the scleral post-equatorial region, followed by micro incision vitrectomy surgery (MIVS), which he says is usually a 23-gauge PPV. “If the retinal detachment is fresh with no PVR, then after complete vitrectomy, fluid-gas-exchange (FGE) and endolaser, I inject C3F8/SF6 gas as a postoperative tamponade,” explained Dr. Kumar. “Gas helps to keep the break closed with its effect on surface tension.” For intraoperative viewing, Dr. Kumar says that NGENUITY 3D Visualization System (Alcon, Fort Worth, TX, USA) is the gold standard: “[It] helps me obtain higher magnification for viewing as I sit straight and watch the large screen displaying the surgery . . . and it helps me to be sure that the retina has flattened, and that macular holes are bridged by ILM tissue,” he continued. “It looks at any iatrogenic breaks too, which may have been inadvertently created during macular membrane peeling. My residents and fellows also observe the same surgical steps, which add to their surgical training.”
Golden Innovations Could Elevate RD Treatment According to Dr. Kumar, there are new innovations in the pipeline that can elevate the gold standard of RD surgery further. Things including improved non-toxic dyes – like plant-based dye – would be useful for staining the epiretinal membrane (ERM) and internal limiting membrane (ILM). “Presently, I use brilliant blue G dye, which is effective and only stains the ILM,” explained Dr. Kumar. In addition, he says to raise the bar higher, new instrumentation would be helpful: “Multi-function instruments with both aspiration and diathermy for bleeders during diabetic vitrectomies; hooded wide-angled endolights; superiorly designed chandelier lights to prevent glare; and biologic glues/ embryonic tissue to seal retinal breaks could be of some additional help.” In the years to come, new
therapeutic innovations will surely continue to advance methods and options of treatment for vitreoretinal conditions – altering the gold standard in the way diseases like DR and complications like RRD are treated. Technologies, like handheld/ smartphone imaging devices, machine learning and AI, should also play a key role in providing more access to screenings, creating opportunities for disease prevention, early detection and prompt diagnosis and treatment.
1 Das T, Panda L. Imagining eye care in India (2018 Lalit Prakash Agarwal lecture). Indian J Ophthalmol. 2018;66:1532-1538. 2 Corcóstegui B, Durán S, GonzálezAlbarrán MO, et al. Update on Diagnosis and Treatment of Diabetic Retinopathy: A Consensus Guideline of the Working Group of Ocular Health (Spanish Society of Diabetes and Spanish Vitreous and Retina Society). J Ophthalmol. 2017;2017:8234186. 3 Gadkari S, Maskati Q, Nayak B. Prevalence of diabetic retinopathy in India: The All India Ophthalmological Society Diabetic Retinopathy Eye Screening Study 2014. Indian J Ophthalmol. 2016; 64(1):38-44. 4 Takkar B, Azad SV, Bhatia I, Azad RV. Late presentation of retinal detachment in India: A comparison between developing nations. Natl Med J India.2017;30:116 5 Chandra A, Banerjee P, Davis D, Charteris D. Ethnic variation in rhegmatogenous retinal detachments. Eye (Lond). 2015; 29(6): 803807. 6 Lin T, Mieler W. Management of Primary Rhegmatogenous RD. Review of Ophthalmology. Published July 15, 2018. Available at https://www. reviewofophthalmology.com/article/ management-of-primary-rhegmatogenousrd. Accessed on 16 November 2018.
About the Contributing Doctors Dr. Pushkar Dhir, MBBS, DNB (Ophtha), FICO (I), VR (Fellow), received his medical degree at Christian Medical College and completed his ophthalmology residency at Venu Eye Institute. He is and currently pursuing fellowship in vitreoretinal diseases and surgery from Sri SankardevaNethralaya, India. Dr. Pushkar describes himself as a budding VR surgeon, amateur runner, avid traveler and a reader of his own thoughts. [email: email@example.com] Dr. Abhishek Kothari, MS, FRCS, FICO, FMRF, is a consultant vitreoretinal surgeon in Jaipur India. He completed his undergraduate at Coimbatore Medical College and ophthalmology residency at S.M.S. Medical College, Jaipur. Dr. Kothari completed a fellowship in vitreoretinal surgery at Sankara Nethralaya, Chennai, and worked at the world renowned Aravind Eye Care System in India before moving to his current position. He has considerable experience as a practicing vitreoretinal surgeon. [email:firstname.lastname@example.org] Dr. Atul Kumar, MD, FAMS, FRCS (Ed), chief and professor of ophthalmology at the All India Institute of Medical Sciences (AIIMS) in New Delhi, India, where he completed his MD and Sr. residency. Dr. Kumar completed his retina fellowship at the University of Maryland in Baltimore, USA in 1990. He has currently authored more than 278 indexed and non-indexed publications and has received numerous awards. [email: email@example.com]
Mozart and Opht halmology at EURETINA-ESCRS 2018
Team PIE at EURETINA, where serious ophthalmic business is underway
“Dr. Mozart” checks out Rafiq Hasan, VP and Global Head, Ophthalmology, Bayer
With Jim Mazzo, Global President of Ophthalmology, ZEISS
INNOVATION OPHTHALMIC TOOLS
Robots May Soon Take Over Surgeries . . . by Hazlin Hassan
obots may soon take the scalpel away from surgeons and revolutionize surgery – along with other cutting-edge technologies like artificial intelligence (AI) and smart sensors. These are just some of the latest surgical innovations discussed during the PIE Talks series at EURETINA 2018, which took place in Vienna, Austria in September. “If we look at vitreoretinal surgery, we have reached more or less the limits of what we are able to do with our instruments,” said Dr. Marc D. de Smet, founder and chief medical officer of PRECEYES BV, based in Eindhoven, The Netherlands. His company develops next generation medical robotics and has created the PRECEYES Surgical System to assist eye surgeons and perform tasks, like vitreoretinal surgeries. With several advantages over humans (including higher cutting accuracy and precision), robotics could take over the operating theatre. “If you operate, you have in your best years about 100 microns worth of tremor. It is 100 times better if you let the robot carry out the surgery,” said Dr. de Smet. Delicate retinal surgery often requires precise fine motor control to achieve the best results and reduce surgical risks. Any accidental movement could result in ocular injury. The possibility of integrating the system with intelligent sensors would also revolutionize the field. According to Dr. de Smet, sensors would tell surgeons exactly how far they are from the retinal surface: “So, it tells you if you are going to do something that puts you in the danger zone. You would be able to anticipate just like if a pilot is going too fast and too close to the landing strip, there are warning signs and bells that go off in the cockpit . . . we could do the same thing, so it will make the surgery safer,” he said.
Meanwhile, Dr. Rafiq Hasan, vice-president and global head of ophthalmology at Bayer, also believes robotics could be the way forward. “We are hearing about some really great advances there,” he said, adding that a group in Switzerland is developing a robot that could, in the future, carry out injections in the eye. Patients with age-related macular degeneration need regular injections, and these are currently administered by trained doctors. With robotics, the injection could be much safer and more precise. “‘The heartbeat itself can cause a slight tremor, and when you are dealing with something as delicate as the eye, the ability to remove that tremor using robotics could be significantly advantageous in how a clinician operates on the eye,” said Dr. Hasan.
“You have greater assurance that they are injecting in the right place, and at the same time, injecting the right volume. There are many ways in which I think we can combine that skill of the clinician with technology to improve how we manage patients,” added Dr. Hasan. He also noted that there has been a lot of progress in AI over the last year or two, with a big movement in the United Kingdom in that direction. Moorfields Eye Hospital (London, United Kingdom) is currently looking at whether AI algorithms could help physicians understand and interpret optical coherence tomography (OCT) images. Patients can be screened remotely using this method and see a physician only if they need to. Dr. Hasan said that Bayer is currently working on a tool to improve patient education
and outcomes. “Almost 50 percent of diabetic macular edema patients were discontinuing with treatment even though they are aware that they are at risk of going blind and effective injections are available,” said Dr. Hasan. “Something that we have been working on is an app that patients can use alongside treatment to better understand how they are progressing, to understand why they have this disease, the underlying mechanism, so we think better patient education, better engagement with their condition and their treatment will lead to better outcomes,” he added. Mr. Rod Ross, chief executive officer of Med-Logics Inc, Texas, USA, talked about his company’s CataPulse incision device, heralding a new generation of cataract surgery. Designed
to do away with ultrasound energy, this phaco-free technology is focused on minimizing the risks of surgery. Most cataract procedures involve the use of a high-frequency ultrasound device that breaks up the cloudy lens into small pieces, which are then removed. The procedure, called phacoemulsification or “phaco,” can be performed with smaller incisions, promoting faster healing, and reducing the risks of cataract surgery complications, such as retinal detachment. Ultrasound is the cause of many cataract complications, which is what led Mr. Ross to develop the CataPulse, which also makes smaller incisions. “We have used it in surgery prototypes for seven years with zero complications. That’s where cataract surgery needs to be. We have got to try to eliminate the complications. Patients want rapid visual recovery, and small incisions, they do not want complications,” said Mr. Ross. On the other hand, Armond Dantino, vice-president of sales at MacuLogix Inc, Florida, USA, said his company has created the only fully automated dark adaptometer commercially available. It can detect age-related macular degeneration (AMD) up to three years earlier, potentially improving patient treatment and providing a better chance at preserving vision. This is crucial, as AMD is a massively growing disease, with 200 million predicted cases by 2020. Early and intermediate stages of AMD often present no symptoms, and it can cause the loss of central vision. “We want to identify early and hopefully save sight. That’s the whole goal of our company, to provide eye care practitioners with equipment to save sight,” said Mr. Dantino. Early detection is important, as researchers have found links between the disease and lifestyle choices such as smoking. “If you know you have AMD early, you can change your lifestyle, you can stop smoking, you can exercise, you can eat a good Mediterranean diet
with fruit and vegetables. If you believe in nutraceuticals and antioxidants, you can take those as well. If you can maybe push off the progression of the disease as much as you can, it gives you better outcomes later on in life,” added Mr. Dantino. In addition, James Mazzo, global president of ophthalmology for Carl Zeiss Meditec AG says that the power of AI can be harnessed to assist doctors in diagnosing patients, which would help to overcome the problem where there are more patients and fewer doctors. “Today, doctors don’t have the availability, they don’t have the time to see every one of the patients,” he said. “If we can use AI to take some of the menial tasks out of our great physicians’ hands and allow them to use more of the capacity of the brain, the patient wins,” he said. This in-depth knowledge can make all the difference to diagnosing a patient. For Dr. Diva Kant Misra, ophthalmologist from Sri Sankardeva Nethralaya, Guwahati, India, Alcon’s NGENUITY 3D Visualization System which uses a head-up high definition 3D screen for vitreoretinal surgeries is the future, along with AI and robotics. “I am sure these technologies (robotics and 3D) will integrate at some point in time. Like we have intraoperative OCT, we have 3D visualization, we are doing ILM (internal limiting membrane) peeling with the help of robotics. So, all of these into one, I am sure it will be a great combination. Such technologies would likely have better results for the patient,” said Dr. Misra. “We would have more predictable results, and it’s better for the patient. That has to be the priority,” he added. Editor’s Note: This article is an excerpt from PIE Talks 2: Mozart and Ophthalmology, interviews conducted at the EURETINA-ESCRS 2018 joint congress held in Vienna, Austria. Search YouTube for “PIE Talks Episode 02” for the complete videos of the individual interviews.
EIDON WideField TrueColor Confocal Scanner
A Breakthrough in Fundus Imaging
etinal Imaging is playing an increasingly important role in ophthalmology. Technical advances in this field are leading to radical changes in the diagnosis and monitoring of several retinal pathologies, and in the objective assessment of responses to treatments and surgery. The introduction of EIDON Wide field TrueColor Confocal Scanner (by CenterVue; Padova, Italy) to the market has set a new standard in retinal imaging. The device uses confocal technology and white LED light illumination, a unique combination that offers detailsrich images and high-fidelity to actual retinal colors. This provides eye care practitioners with an authentic perception of the retinal anatomy, giving all those details which can aid in the detection, diagnosis and follow-up of pathologies. Yoshitaka Oka, M.D, from the Oka Eye Institute, Fukuoka, Japan, emphasized that a high-quality imaging system such as this is a very valuable tool to educate patients about the need to better manage their condition through treatment or surgery, and to better explain to them the need for further examinations. “EIDON arrived to my clinic in September 2016, and immediately became an indispensable device in my clinical practice,” shared Dr. Oka. “In fact, EIDON has allowed me to obtain a completely new and different concept of a wide-field, high-resolution retinal image – one that represents a real breakthrough compared to any other fundus camera or scanning laser ophthalmoscope (SLO) system available in the market today,” he added.
Superior Image Quality The primary benefit of EIDON confocal technology is the superior and unique-inits-kind image quality that facilitates and improves the detection of changes in the retina. It is known that early signs of retinal diseases may be missed with a direct examination or with low resolution fundus imaging systems. However, EIDON’s detail-rich images, even through cataracts or other media opacities, aid in detecting the slightest morphologic abnormalities.
According to Dr. Oka, EIDON’s technology makes it the perfect tool to
image and document pathologies, like in the screening of diabetic retinopathy. The high-resolution images generated by EIDON enable surgeons to conduct an examination over time of the smallest symptoms of diabetic retinopathy (DR) – symptoms like microaneurysms, dot hemorrhages and retinal neovascularization – that are otherwise hard to detect in standard fundus camera and direct ophthalmoscopy examination. “This is why I think EIDON is also the perfect tool for DR screening and DR stage evaluation,” he said. Also, the sharpness of the images in EIDON, due to its confocal optical engine, is able to clearly show the wrinkling of the retinal surface and the thinnest superficial retinal folds typical of the epiretinal membrane (ERM). “All these details are generally not distinguishable or completely lost in a typical fundus camera image. This is why I can certainly state that capturing the ERM is one of the most valuable capabilities of EIDON,” said Dr. Oka.
Imaging in Difficult Visualization Conditions Even in difficult imaging conditions, such as in cases of cataract and small pupils, EIDON’s confocal technology still allows the instrument to take an image of the retina, where traditional fundus cameras cannot (a crucial limitation in several cases). “More importantly, EIDON is able to take an image of the fundus through a poorly dilated or non-dilated pupil (down to 2.0 mm), allowing for improved patient flow, facilitating operator activities and reducing patients’ waiting times,” explained Dr. Oka.
Wide-Field View EIDON provides an 89-degree image of the retina with a single exposure. In addition, multi-field imaging allows for the automatic creation of a 163-degree montage: an essential tool in managing and follow-up peripheral lesions. EIDON TrueColor confocal technology applied to wide-field imaging improves the detection, analysis, and monitoring of pathologies affecting the peripheral retina, preserving the sharpness and details of the pictures even
in the periphery accurately documenting the extent and location of these diseases.
Ease of Use The device is very easy-to-use and requires minimal operator involvement: in full automatism it aligns the patient’s pupil, focuses on the retina, and captures a single 89-degree image of each eye, taking less than one minute. “At the same time, the device is also very comfortable for the patient, since it uses a non-intense light source that softly flashes the patient’s eye,” explained Dr. Oka.
Multiple Imaging Modalities EIDON technology supports different imaging modalities. In addition to the unique TrueColor imaging option, the device also allows the acquisition of infrared, red-free and autofluorescence (optional) photographs of the retina. “Autofluorescence imaging in particular provides interesting support in the diagnosis of several diseases, since it overcomes the evaluation of the simple retinal anatomy, opening a window in the evaluation of retinal metabolism (without the risk of allergic reactions due to fluorescent dye, as in fluorangiography),” Dr. Oka concluded.
Figure 1. 89° retinal image taken using Eidon before surgery
Figure 2. 89° retinal image taken using Eidon after surgery
This article has been supported by an educational grant from CenterVue.
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ENLIGHTENMENT WOMEN IN OPHTHALMOLOGY
Spreading Her Wings in
by Tan Sher Lynn
Basak Deveci Summer proves that a woman can soar in the male-dominated field of ophthalmology as long as she keeps her chin up and strives on.
asak Deveci Summer has worked in the ophthalmology industry for 11 years, and the 36-yearold medical biologist is associated with Biotech Vision Care Pvt Ltd (Ahmedabad, India)* – she’s responsible for clinical affairs and training in Europe, the Middle East and Africa (EMEA). “My responsibilities include designing study outline, program and protocol feasibility, selecting appropriate site and managing clinical research assistants (CRAs) who are monitoring clinical trials on a day-to-day basis in the clinics. Besides, I provide support for the marketing team in the form of medical writing of product brochures, presentations, doctors’ presentations for congress and so on. I also train surgeons and sales teams on new products in my area,” she shared. Within five years of working in Biotech Vision Care, Ms. Summer has published five studies about their products, with more in the pipeline. “The process of having a publication in any ophthalmology or medical journal is a challenging and time consuming process wherein a lot of data is needed to be collected within
a certain period of time, before being submitted to the ethical committee along with a clinical study protocol to obtain an approval according EU regulations. Publishing a study means at least two years of effort to complete all the steps and have a manuscript written by the investigator,” she explained. She had also been in-charge of organizing the Biotech Dinner Event and Lunch Symposium at the Congress of the European Society of Cataract and Refractive Surgeons (ESCRS) in 2017 & 2018, respectively.
Discovering Her Passion Interestingly, Ms. Summer had never planned to work in the field of ophthalmology. Having graduated with a bachelor’s degree in medical biology, she wanted to pursue a master’s degree in molecular biology, but wasn’t able to do so due to financial constraints. So, she sought out work and was hired by a Turkish company that distributed Zeiss, Ophtec, Mediphacos, Moria and Avedro products.
“I was hired as an application specialist. In that position, I travelled a lot. I attended trainings provided by manufacturers of high technology devices and with the knowledge that I gained, I explained to and trained doctors about the devices, treatment planning and patient selection. I also attended many surgeries which involved devices like the excimer laser, femtosecond laser, microkeratomes, phakic IOLs, intrastromal corneal rings and so on,” she said, adding that, due to her scientific background, she was able to improve her understanding of ophthalmology quickly and soon fell in love with it. After six years, she resigned from the company and had a short stint working in the international marketing team of the Bir Inci Eye Hospital in Istanbul before being offered to take up the position of assistant manager in clinical affairs and training, EMEA, by Biotech Vision Care. She was subsequently promoted to the role of manager. “Working in this field, I realized how precious our sight is. When we can see, we often take our sight for granted. Ophthalmology is amazing as it deals with a very delicate organ and arguably the most important sense of human being. This field is also very interesting and challenging due to the many innovations and development in terms of technology. Things are advancing very fast and there are new
Basak Deveci Summer, at right
things every day that I need to read about, understand and discuss with my colleagues.” “When I first started my career, there were only microkeratomes to create a LASIK flap. Later, the femtosecond laser for flap creation came into existence. Subsequently, the femtosecond laser was also used for cataract surgery, and now we are talking about Zepto for capsulorhexis or SMILE for myopic and astigmatic correction. All these happened in merely 10 to 12 years,” recalled Ms. Summer. She is also in awe of the wonders and miracles in this field. “It’s always wonderful to see the reaction of patients with high myopia after a phakic IOL implantation, the happiness of young patients who see the world clearly for the very first time after a vision correction procedure, the wow reaction of LASIK patients for being able to see clearly without glasses, and the joy of cataract patients for feeling young once again after trifocal IOL implantation,” said Ms. Summer. “Moreover, today, we are seeing a higher percentage of women working in ophthalmology compared to other medical disciplines. A professor once told me that almost one-third of the all ophthalmologists are women and it makes the industry sort of more ‘civilised’, because, if there are enough women in any group, the behavior of men in that group will change for the better and there will be more collaboration, which leads to better results.”
Rising Up to the Challenge Ms. Summer acknowledges the challenges she faces in her career for being a woman. “I guess, like many
other industries, the inequality lies in terms of salaries, getting a promotion and getting hired. Throughout the 11 years in this industry, I was invited for job interviews by local and international companies on a few occasions. Interestingly, after the interviews, even though I was told that I was one of the two best candidates, the male candidate got hired. I believe that because of my gender, it was a concern that I may get pregnant and leave the work for four to six months, or I may not travel as often as they like,” she explained. “As a woman, I have to convince people that I could achieve any task and overcome the challenges as much as male counterparts can. Getting a chance at any task is the most challenging part. So, whenever I get a chance to do something, I have to be extremely careful as not to fail. As far as I have observed, there is almost zero second chance for women in this industry.” “Positions which are similar to mine are mostly filled by men because there’s a lot of traveling to do. Hence I also need to convince everybody I could travel as much as needed,” said Ms. Summer, who travels for five to 15 days a month. She attributes her ability to travel so much to the support provided by her husband whom she has been happily married to for the past two and
a half years. “My husband is always supportive whenever I am working hard on my projects. Instead of complaining that I am spending too much time in work, he always encourages me to achieve my very best,” she shared. Ms. Summer’s favourite quote is: “Never give up, never give in.” “As a woman especially, we need to keep our chin up and work hard. We need to accept the fact that discrimination towards women has been a problem since ancient times in all societies. Nevertheless, we as women shall keep trying and showing to everyone that we can achieve tasks, manage people and situations in a very kindly and efficient manner. As a woman in this age, we are in a better situation than any woman 50 years ago. We need to remember the past efforts of the women before us and continue this legacy for future generations,” she said. *Biotech Vision Care Pvt Ltd is part of the Biotech Healthcare Group (www. biotechhealthcare.com).
About the Contributor Basak Deveci Summer is the Manager of Clinical Affairs and Training for Europe, Middle East and Africa of Biotech Vision Care Pvt Ltd. She holds a bachelor degree in medical biology from the Istanbul University Cerrahpasa Medicine Faculty. Within five years of working in her current company, she has published five clinical studies about their products. She is passionate about ophthalmology and hopes to see more investment in improving low vision or blindness in children, an area that she felt is lacking due to lower financial profit. She currently resides in Istanbul, Turkey with her husband, whom she loves to take long walks with around the city.
ENLIGHTENMENT CHARITIES FOR THE BLIND
for the Visually Impaired
social support (like senior citizen homes and employment placements), and information resources (e.g., Braille and audio library, Braille transcription service and online learning). “By participating in Kind Malaysia, we hope to connect with the corporate world to forge long term relationship that will further our mission,” concluded Mr. Soon.
The Malaysian Association for the Blind – Creating Equal Opportunities
by Tan Sher Lynn
f all the five senses, some would say that the most important is vision. Humans perceive up to 80% of all impressions through sight, making it crucial to prevent visual impairment, as well as assist those already affected by blindness. At UBM Malaysia’s inaugural CSR exhibition – called Kind Malaysia – we spoke with three organizations dedicated to supporting the visually impaired and blind community. The event was created to highlight and promote the importance of kindness between like-minded individuals from non-profits, small-to-medium sized enterprises and large corporations.
St. Nicholas’ Home – Toward a Nation Free of Barriers Established in 1926, St. Nicholas’ Home is a social concern ministry under the Anglican Diocese of West Malaysia. It is the first organization to serve the blind and visually impaired
community in Malaysia. “Our mission is to work toward a nation free of barriers, where blind and visually impaired persons are not discriminated against, but have the same rights and responsibilities, equal opportunities and quality of life that is available to their sighted peers,” said Daniel Soon, who became executive director of St. Nicholas Home in 2010 and has since introduced many new initiatives. “We strive to achieve our mission by providing education, training and employment opportunities, as well as a caring environment, to empower the blind and visually impaired to fully participate in society . . . while also helping to promote the prevention of blindness,” continued Mr. Soon. Services provided at St. Nicholas’ Home include: The Early Intervention Programme and Task St. Nicholas’, rehabilitative training, vocational training (i.e., IT, massage, pastry-making),
Established in 1951 by the Department of Social Welfare, The Malaysian Association for the Blind (MAB) serves the visually impaired by providing services that improve their quality of life. MAB takes care of the general well-being of blind persons in the country by providing them with educational programs; rehabilitation courses; vocational training (like industrial work, computer programming and woodwork); and placement services to help them secure employment and live independently. The association also runs a Braille library, a Braille Publishing Unit, an Information Technology Centre, Resource Centre and a Sale and Production Unit. MAB also has its own eye hospital to carry out its blindness prevention programs and advises and makes recommendations to the government and relevant authorities on all aspects concerning the visually impaired. “In recent years, through community-based rehabilitation schemes, MAB has reached out to visually impaired folks in rural areas in order to provide them with rehabilitation services and training programs within their home environment,” said MAB Sales Executive Muhammad Izzat. In order to accommodate the changing needs, demands and challenges of the modern world, MAB constantly strives to improve and expand its services for the betterment of visually impaired people by introducing new courses and acquiring new equipment. “We always work toward
creating greater public awareness concerning the abilities and capabilities of the visually impaired persons under our wings to ensure better integration into the society and quality of life,” added Mr. Izzat. “By exhibiting in Kind Malaysia, we hope to make our presence and activities known to more potential donors so that we can serve more visual impaired people in Malaysia,” he said. “Just as MAB tries to provide a platform for the blind and visually impaired to function well in society, at the same time, we need society to support us for us to grow.”
National Council for the Blind – Working Together to Help the Blind In a joint effort to serve the blind and visually impaired, the National Council for the Blind (NCBM), Malaysia was founded in 1984 by five NGOs in the different regions of the country: St. Nicholas’ Home Penang, the Society of the Blind, the Sabah Society for the Blind, the Sarawak Society for the Blind and the Malaysian Association for the Blind, “The objectives of NCBM include the introduction and progressive improvement of policies and implementation of services governing education, rehabilitation, employment and general welfare of the blind, as well as pertaining to prevention of blindness in Malaysia,” said NCBM Executive Director Moses Choo. NCBM’s initiatives include coordinating activities of member organizations to facilitate cooperation; organizing forums for consultation and discussion; reviewing progress in the fields of education, braille literacy, vocational training, employment, blindness prevention, and other programs for the blind in Malaysia; and soliciting the support of the government and other agencies for services and programs to be carried out for the socioeconomic advancement of the blind. “We also look into the implementation of software to assist the blind and recently, we are moving
toward the use of apps on smart phones. We achieve this by working together between organizations and maximizing all our resources. With this effort, we hope that no blind person is left behind,” explained Mr. Choo. “Participation in Kind Malaysia will allow us to continue our advocacy work, which is keeping the sighted world informed of the progress of the blind community, with the hope of making society more inclusive. When the blind are accepted into society and allowed to work side-by-side with people of normal vision, there will not be a need to place the blind under welfare services,” he continued. “Time and time again, the blind have proven that they are able to be successful. They can hold responsible jobs and maintain a family. There are blind people who are lawyers, lecturers at institutions of higher learning, as well as in business and politics, like prominent ex-UK minister David Blunkett,” said Mr. Choo, who is visually impaired himself.
Editor’s Note: Kind Malaysia 2018 took place on 24-25 October 2018 at the Malaysia International Trade and Exhibition Centre (MITEC) in partnership with #myWorld by MITEC.
About the Contributors Daniel Soon has been executive director at St. Nicholas’ Home since 2010. He started his career in the specialized field of structural steel engineering in the mid-80s upon completing his diploma. Over his 20-year construction career, he managed many major private and public projects all over Malaysia. He became a board member of St. Nicholas’ Home on voluntary basis in 1997 and served as a subcommittee chairman for many years. He has introduced and presided over many new initiatives and programs at St. Nicholas’ Home. [Email: firstname.lastname@example.org]
Muhammad Izzat Amirul Md Saidey is the sales and woodwork executive of the Malaysian Association for the Blind (MAB) responsible of managing the sales and production of wood and rattan craft made by visually impaired persons. He holds a Bachelor of Forestry Science (Wood Technology and Industry) from the University Malaysia Sabah. [Email: email@example.com]
As the executive director of the National Council for the Blind Malaysia (NCBM), Moses Choo oversees most operations of the organization. Prior to joining NCBM nearly 16 years ago, he worked in companies such as TriCor and PricewaterhouseCoopers, where he progressed from a telephone operator to the post of admin manager. After that, Mr. Choo joined NCBM with the hope of using his experience to enhance the organization’s work. [Email: firstname.lastname@example.org]
ENLIGHTENMENT MUSEUM OF VISION
New Eye Museum to
Wow Public in 2020 S
oon, ophthalmologists won’t be the only ones to experience eye surgery first hand. That’s because the world’s first major public museum dedicated to vision and eye health is set to open in the United States by 2020, providing a place where anyone can walk in and learn about the eye. This new project is an extension of the already existing Museum of Vision, which serves as the history and archives department of the American Academy of Ophthalmology (AAO),
David W. Parke II, M.D.
housing its 38,000-piece collection of artifacts, books and instruments, which have been collected for more than 30 years. It is an important educational resource for Academy members, medical historians, researchers and the public, but opportunities to view the archives are limited to a yearly exhibit at the Academy’s annual conference. An appointment is also needed for visitors to the museum. Now, that’s changing. The first of its kind, this free museum offers an immersive experience for both children and adults, with virtual reality headsets and interactive touch screens, where visitors will get to learn about the history of medical and surgical eye care, as part of efforts to help the public understand their own eye health. Members of the public will get to learn about instruments and even know what it is like to carry out a cataract operation.
David W. Parke II, M.D, chief executive officer of the AAO, recently announced plans for the new museum at the 2018 AAO Congress: “The museum has been a treasure of the Academy for many, many years, and it exists right now because of the work of an incredible group. We have a tremendous heritage as a profession, as ophthalmologists. We’ve got wonderful things: artifacts, instruments, books, things that are really the heritage of our profession,” he said. “We haven’t been able to share it, they have been in closets, storage vaults, and there has always been this vision in the background that we are going to do something about that. But we are now,” explained Dr. Parke. The new museum will be built at the AAO headquarters in San Francisco – and it will not just be about dusty history books and tools. It will showcase the latest in technological advances,
medical breakthroughs and cuttingedge technologies . . . all of which are saving the eyesight of millions of patients around the world each day. “Most people don’t know what ophthalmology is or how ophthalmologists protect sight,” said Dr. Parke. “The new Museum of Vision will be the first-of-its-kind where the public can go to learn about sight, to see it, to touch it.” Hopefully, the museum will help to inspire future generations of eye doctors and surgeons. “For thousands of years, ophthalmology has pushed the envelope, discovering breakthrough innovations to protect sight,” said prominent ophthalmologist Stanley M. Truhlsen, M.D. “The museum is the vehicle by which our heritage remains both relevant and inspiring; promoting continued discovery and advancement.”
Dr. Truhlsen, who gifted the project with a $4 million donation, is a past AAO president. He is also a university educator and recipient of the prestigious Lucien Howe Medal for ophthalmic service. An estimated 30,000 visitors a year are expected to walk through the planned 3,500-square-foot museum in the heart of a major tourist destination, Fisherman’s Wharf in San Francisco, California, USA.
Editor’s Note: The American Academy of Ophthalmology (AAO) is the world’s largest association of eye physicians and surgeons. A global community of 32,000 medical doctors, it aims to protect sight and empower lives by setting the standards for ophthalmic education and advocating for patients and the public. It innovates to advance its profession and to ensure the delivery of the highest-quality eye care. For more information, visit aao. org. The Academy’s Museum of Vision is the largest publicly accessible collection of ophthalmic history in the United States. With the support of the American Academy of Ophthalmology Foundation, the museum’s collection of 38,000 artifacts helps to preserve ophthalmic history and celebrate its unique contributions to science and health in preventing vision loss. For more information, visit aao.org/ museum-of-vision.
CONFERENCE HIGHLIGHTS APVRS 2018 PREVIEW
SEOUL Welcomes Delegates
by Brooke Herron
his year, Seoul, Korea hosts the 12th meeting of the Asia-Pacific Vitreo-retina Society (APVRS). Held from December 14 to 16, the three-day congress will attract delegates from around the world with a broad scientific program and symposia from the region’s foremost retina experts. “Over the years, the APVRS Congress has grown in stature and in scientific content as one of the key ophthalmology conferences in the Asia-Pacific region, attracting leading vitreoretinal specialists from around the world to share their knowledge and experience,” said Dr. Dennis Lam,
President of the APVRS.“With so many renowned speakers, the Congress will provide excellent opportunities to gain insight into the latest discoveries and innovations in the vitreoretinal field.”
A Golden Scientific Program According to 2019 Congress President and President of the Korean Retina Society Dr. Won Ki Lee, this year’s program features high-quality scientific sessions and discusses the latest research findings and issues in vitreo-retina. In addition to 22 invited symposia, there are also submitted sessions, including free papers and instruction courses.
Attendees should take note of the three award lectures.The APVRS Tano Lecture honors an individual over 45-years-old for exemplary leadership and significant contributions in advancing the understanding, diagnosis and treatment of vitreoretinal diseases. The 2018 lecture will be given by Dr. Masahito Ohji and is titled: “Submacular Hemorrhage: Where Are We Now?”. Dr. Ohji is the chairman of the Department of Ophthalmology at the Shiga University of Medical Science Seta Tsukinowacho in Otsu, Japan. This lecture follows the Opening Ceremony on December 14.
The APVRS Constable Lecture is presented to an individual under 45-years-old who has also made significant contributions in the field of vitreo-retina. Dr. Gemmy Cheung will give this award lecture, called: “PCV — A Focus on What We Don’t Know”. She is the deputy head and senior consultant of the medical retina service for Singapore National Eye Centre (SNEC), as well as senior clinician investigator for the Singapore Eye Research Institute (SERI). Dr. Cheung’s research interests include the study of risk factors and clinical features of macular diseases that may be unique to Asian populations. Dr. William Mieler, the Director of Ocular Oncology Clinic at UI Health (Chicago, USA) and the Cless Professor in Ophthalmology, will give the APVRS International Award lecture. Established in 2017, this honors experts who fulfill the criteria of the other two awards (with no age restriction), but who are from beyond Asia-Pacific. Dr. Mieler’s lecture is titled: “The Impact of Systemic Medications on Retinal Function”. He is an expert in treating diseases of the macula, retina and vitreous. A final lecture will finish this series: the KRS Hyung-Woo Kwok Lecture (speaker details unavailable at press time). In addition to these lectures, the APVRS Congress will present awards for the best abstracts in free posters (five awards), posters (three awards), e-posters (three awards), and videos (three awards).
Annual Congress provides a platform to network and establish collaborations and friendships,” said Dr. Lam. Indeed, APVRS has an exciting social program planned for delegates, including the Opening Ceremony, Presidential Dinner, Congress Party and Closing Ceremony. “This congress will allow you to learn the latest issues in vitreo-retina, as well as network with colleagues,” added Dr. Lee. Dr. Lam says to also take some time to enjoy the city: “Seoul is a vibrant city, known for its advanced technology, popular music and delicious street food.” A huge, modern city with a population of about 10 million, Seoul ranks high as a tourist destination. Both trendy and traditional, towering skyscrapers meld with Buddhist temples and palaces, creating an urban environment like no other. Located in the popular Gangnam district, the event venue – Coex Convention and Exhibition Center – is not only well-recognized as events center, but a tourist attraction as well. For attendees needing a dose of retail
therapy (or pop culture), the venue is connected to Coex Starfield Mall, an undergroundshopping mecca with a large movie theater complex and numerous fine dining restaurants. Also located near Coex, is Bongeunsa Temple, constructed in 794, and home to 3,479 Buddhist scriptures. Admission is free, and the temple is open yearround. The Gangnam district is also home to several green, recreation areas including tourist destination Olympic Park, as well as Seonjeongneung Park, which is home to royal tombs. Clearly, this meeting, with its exciting scientific program and location in the dynamic capital city of Seoul, should not be missed. Through this Congress (as well as other initiatives), the APVRS strives to assist the development of the vitreo-retina subspecialty in Asia-Pacific and to provide a platform for retina specialists to share information – not only with other ophthalmologists, but with the general public too. For more information about APRVS 2018, visit www.apvrs.org.
City Lights and Social Nights In addition to the impressive scientific program, APVRS also provides an opportunity to connect with friends, colleagues and business associates from around the world. “The APVRS
CONFERENCE HIGHLIGHTS APVRS 2018 PREVIEW
‘Goes for the Gold’ in Seoul by Brooke Herron
ith its impressive scientific program, the 12th meeting of the Asia-Pacific Vitreoretina Society (APVRS) is bound to be a groundbreaking congress. The city recently hosted the 2018 Winter Olympic Games – and in the spirit of ‘going for the gold’, we’ve uncovered a ‘goldmine’ of informative sessions and symposia, free papers and posters/eposters from the region’s leading retina expert. “The 12th APVRS Congress has invited renowned speakers and moderators, not just from the AsiaPacific region, but also from around the world, in various subspecialties ranging from age-related macular degeneration and polypoidal choroidal vasculopathy, diabetic macular edema, pathological myopia, retinal dystrophy, intraocular tumors, uveitis, to ocular trauma,” said Dr. Won Ki Lee, president of the 12th APVRS Congress and president of the Korean Retina Society. “The distinguished speakers will deliver their presentations on diagnoses, therapeutics, imaging modalities or operation procedures, which no doubt will lead to extensive discussion among colleagues in the vitreo-retinal field.” In addition, this year’s congress also includes a ‘golden’ symposium on “big data,” which according to Dr. Paisan Ruamviboonsuk, has recently sparked tremendous interest in both the medical and non-medical fields. “Harnessing big data through analytics with combination of artificial intelligence (AI) and machine learning may yield invaluable answers to epidemiologic, basic research, clinical practice questions, etc., and hence drive improvements in patient care. These innovative approaches will be an enlightening adventure for both
comprehensive ophthalmologists and retinal specialists,” said Dr. Ruamviboonsuk, who serves as the chair of the scientific program committee.
Invited Symposiums Raise the Bar This year, more than 500 abstracts were submitted for free paper and poster consideration. These – along with the invited symposia and award lectures – create a truly remarkable scientific program. Here’s a sneak peek of some of the sessions.
Retinal Vascular Disease. Delve deep into the management of retinal vascular diseases with this symposium. Topics include the role of diagnostic imaging tools (like wide-field imaging, optical coherence tomography angiography); the impact of AI; and advances in imaging and treatment of macular telangiectasias. In addition, trial-based and real-world treatment strategies (including antiVEGF injections, steroid implants and lasers) will be presented.
Controversies in Retina. Explore challenging and controversial issues faced by posterior segment surgeons in this symposium. Covering a range of topics, expect to hear about the latest diagnostic and surgical imaging instrumentation; micropulse lasers; treatment options for proliferative diabetic retinopathy (PDR); pros and cons of surgical techniques for floaters and myopic traction maculopathy; and the impact of AI in ophthalmology. Diabetic Retinopathy Symposium: DRCR.net. Sponsored by the National Institutes of Health, the DRCR Network is dedicated to multi-center clinical research of diabetic retinopathy, macular edema, as well as other retinal diseases. During this symposium, recent findings for the management of diabetic macular edema and PDR will be highlighted, with specific relevance to Asian populations. Latest Advancement in Macular Intervention. This session explores innovations in surgical retina, with insights into stem cell implantation, new surgical technologies and the Argus II retinal prosthesis – all potential armamentarium additions to enhance patient care.
Big Data and Epidemiology. As mentioned by Dr. Ruamviboonsuk, this symposium will focus on combining big data with AI and machine learning to allow rapid analysis of large amounts of data. This has potential applications in traditional epidemiology, including use of “real world” surveys, cohort studies, genetic epidemiology and statistical modeling. Management of Anterior Segment Surgery Complications. Suitable for all ophthalmologists, especially trainees, vitreoretinal surgery fellows and general ophthalmologists, this symposium covers common anterior segment surgery complications that affect the posterior and surgical management options. “Since our meeting last year, the field of vitreo-retinal diseases has continued to evolve with medical and surgical treatment options and exciting research,” said Dr. Ruamviboonsuk. “With that in mind, the Scientific Program Committee comprising AsiaPacific, international, and local Korean coordinators, has worked diligently to provide a remarkable range of topics that cover many key issues and major
challenges in vitreo-retinal practice in the world today.” In addition to the congress’s noteworthy symposia, free paper sessions and posters, attendees should also plan to attend the prestigious award lectures – and this year, another has been added: the Hyung-Woo Kwak Lecture. This is in remembrance of Prof. Kwak, a pioneer and inspiration in retinal research. This, along with the Tano, Constable and International Award-named lectures, are certain to be gold. With all of these incredible opportunities for professional development, delegates should balance the scientific sessions with social engagements and entertainment – and thankfully, extra-curricular activities abound at APVRS 2018. The congress’s social program provides ample prospects for networking and celebration, while the dynamic city of Seoul tempts visitors with a modern skyline, ancient temples and pagodas, delicious street food, and shopping. Indeed, APVRS 2018 offers a goldmine of ophthalmic wisdom and skill sharing. For more information about APRVS 2018, visit www.apvrs.org.
Of Mozart, Halloween and AAO 2018 Chicago
CONFERENCE HIGHLIGHTS AAO 2018 COVERAGE
What you Missed
Highlights from AAO
he retina subspecialty day at the recent American Academy of Ophthalmology (AAO) congress in Chicago (USA) included a full scientific program, bursting with current insights, research and innovation for all things posterior segment. Here, we look at a sample of these informative sessions.
Based on a presentation from Dr. John Thompson on “Anterior Segment Complications of Multiple Intravitreal Injections”.
ntravitreal injections are one of the most common intraocular treatments in ophthalmology. Unfortunately, these injections can sometimes result in significant complications in the anterior segment.
Subconjunctival hemorrhages, with an 11.2% incidence in one study, were thought to be caused by elevated systolic blood pressure and pulse rate; patients on anticoagulants appear to have an increased risk. Corneal abrasions have a lower incidence at 0.15%, according to one study, and can result from an abrasion from the lid speculum; the proparacainesoaked plunger contacting the cornea; movement of the needle close to the eye, or with self-induced trauma in an anesthetized patient. Dr. Thompson says diabetic patients and those with basement membrane dystrophies are most susceptible. Corneal or retinal perforation due to sudden patient movement have a low incidence (0.003%) in Dr. Thompson’s experience: “Sudden patient movement is especially problematic in elderly patients with dementia,” he said. Another complication is hyphema (0.02%, according to Dr. Thompson). This can mimic endophthalmitis and use of anticoagulants is a risk factor.
Another condition that can mimic sight-threatening endophthalmitis is noninfectious uveitis – the U.S. Medicare databases lists this at a 0.73% incidence. Of course, endophthalmitis itself also can present with a 0.62% incidence in eyes receiving anti-VEGF treatments. This is compared with 0.10% in the control group. Finally, lens damage can cause acute cataract with an incidence of 0.2% in the MARINA trial and 0% in the ANCHOR trial. Dr. Thompson says this typically involves posterior capsule with focal cataract that progresses rapidly to diffuse lens opacity.
Based on a presentation by Dr. Anat Loewenstein on “What is Actually in the Syringe? Accuracy and Precision of Intravitreal Injections of Anti-VEGF Agents in Real Life”. While many studies focus on the technical aspects of performing intravitreal injections, Dr. Loewenstein and colleagues recognized that only a few investigate the accuracy of
How much medication is your patient actually getting through intravitreal injections?
CONFERENCE HIGHLIGHTS AAO 2018 COVERAGE intravitreal drug volume delivery in this common procedure. In fact, several studies have found that the accuracy and reproducibility achieved with typical syringes varies greatly. The investigators measured volume output of 669 intravitreal injections administered to patients, and calculated the weight before and after expelling the drug. Patients were separated into three groups: Group 1 received prefilled bevacizumab in a 1.0 ml syringe; Group 2 had prefilled ranibizumab in a small volume syringe with low-dead-space plunger design; and Group 3 received aflibercept drawn from a vial by the physician and injected with a 1.0 ml syringe. They found that volume outputs in all three groups were significantly different from the target of 50 µL – this indicates that the delivered volume outputs are different from what was intended. “Precision was highest in Group 2, indicating that a small-volume plunger design may improve precision,” said Dr. Loewenstein. Overall, the authors concluded that current practices for intravitreal injections are highly variable – with significant rates of over- and underdelivery, which could be associated with elevated intraocular pressure or undertreatment of patients. “This is the first study to investigate the accuracy and precision of anti-VEGF agents delivered by intravitreal injection to patients, and its finding illustrate the need for a specially designed syringe for this purpose,” finished Dr. Loewenstein.
treponema pallidum (syphilis), tuberculous uveitis and herpetic retinitis (acute retinal necrosis). Uveitis can also be associated with life-threatening systemic disease, including multiple sclerosis (MS), serious infections, vasculitides, systemic and inflammatory diseases (like Vogt-Koyanagi-Harada (VKH)) and primary intraocular lymphoma. “Among these, first consider entities such as syphilis, VKH, MS and primary intraocular lymphoma,” said Dr. Rao. While it’s rarely required, Dr. Rao says to perform a vitreous and/ or retinochoroidal biopsy if faced with unexplained uveitis etiology. “In patients with compromised immune status and in patients with masquerade entities such as primary vitreoretinal and primary uveal lymphomas, vitreous and rarely retinal and choroidal biopsy may be needed to establish tissue diagnosis for therapeutic interventions,” explained Dr. Rao.
Based on a presentation by Dr. Gaurav K Shah on “Vitrectomy for Diabetic Macular Edema: Why, How and When”.
iabetic macular edema (DME) is the leading cause of visual impairment in developing nations, and the mainstay for therapy includes intravitreal antiVEGF agents. However, there is no current standardized approach for the treatment of chronic or recurrent DME, and repeated injection place a heavy
burden on the patients, doctors and healthcare system. In this presentation, Dr. Shah explores pars plana vitrectomy (PPV) for treating DME. A few reasons to consider this procedure include: eyes with vitreous detachment (PVD) develop DME less frequently than eyes with attached hyaloid; the vitreous may harbor inflammatory mediators contributing to DME; and relieving tractional forces may help improve vitreomacular traction, while oxygenation of tissue may favor arteriolar constriction. Dr. Shah says the internal limiting membrane (ILM) plays a role in the pathology – in fact, a prospective study indicated that IL removal – compared to PVD induction with PPV alone for DME – stabilized visual acuity and improved cystoid macular edema. So, when should PPV be performed? Some advocate for PPV for patients with persistent DME when the central macular thickness is >250 µm, and for those who have a history of two session of either macular photocoagulation or intravitreal antiVEGF. Overall, Dr. Shah concludes: “New studies indicate that PPV may be an appropriate and safe option for DME treatment.” Editor’s Note: The AAO 2018 annual meeting was held in Chicago, Illinois, USA, on 27-30 October 2018. Reporting for this story also took place at AAO 2018.
Based on a presentation by Dr. Narsing A. Rao called, “Three Pearls for Uveitis”.
n an informative session on uveitis, Dr. Rao provided a comprehensive overview of “diagnosis of uveitis entities one should not miss”. Firstly, it’s vital that physicians don’t overlook any infectious etiology. Infectious uveitis can stem from toxoplasmic retinochoroiditis,
We’ve got all the highlight(er)s right there!
CONFERENCE HIGHLIGHTS APAO 2019 PREVIEW
The Countdown to APAO 2019 Begins
by Brooke Herron
reparations for the Asia-Pacific Academy of Ophthalmology’s 34th annual meeting (APAO 2019) are well underway in Bangkok, Thailand. Held in conjunction with the 43rd meeting of the Royal College of Ophthalmologists of Thailand, the event will run from March 6 to 9, 2019. This year’s event will also be cosponsored by the European Society of Ophthalmology (SOE), which includes 44 national ophthalmic societies from around the European continent. Event organizers recently announced the confirmation of both the International Advisory Board and the Scientific Program Committee for APAO 2019. Including experts from AsiaPacific and beyond, these committee members have begun developing a creative and innovative scientific program featuring 17 subspecialties. “With an anticipated number of over 1,000 international experts speaking on all areas of ophthalmology and visual sciences, the APAO 2019 Congress provides an excellent opportunity for delegates to keep abreast with the latest cutting-edge scientific innovations, knowledge, new
medications, surgical techniques and technologies,” said Dr. Dennis Lam, M.D., chair of the APAO 2019 Scientific Program Committee. An attendance figure of at least 5,000 delegates is anticipated. In addition to the scientific program, planning for the social program is also underway. Events include the Opening Ceremony, Welcome Reception, Presidential Dinner and Gala Dinner. There will also be a charity 5km run during the Congress. Three new member societies will also send official representation to APAO for the first time in 2019. APAO has announced two of those societies thus far. One of APAO’s Associate Member Societies is the Asia Pacific Tele-Ophthalmology Society (APTOS), which was founded in May 2016 and aims to promote communication, exchange and collaboration in teleophthalmology. APTOS, led by President Prof. Ming Guang, hopes to reach ophthalmologists who share the same vision to further the use of teleophthalmology to improve eye care in remote areas. The Asia-Pacific Ocular Imaging Society (APOIS), has also joined as an associate member. This
newly formed society aims to facilitate collaboration between ophthalmologists and vision scientists in the region, with a focus on development and application of ocular imaging. APAO 2019 will be held at the Queen Sirikit National Convention Center (QSNCC), Thailand’s first world-class convention and exhibition venue. With a total floor space of 65,000-square-meters, QSNCC has state-of-the-art equipment and facilities, including the exhibition and function area, Plenary Hall, ballroom and meeting room. There is also a business center, restaurants, coffee shops, a food court and a beverage corner on-site. It boasts a convenient location for APAO attendees who are keen to stay nearby. Located in Bangkok’s central business district, it’s situated close to many 3- to 5-star hotels, as well as popular attractions and shopping centers. For more information about the 2019 congress, visit http://2019. apaophth.org. Editor’s Note: PIE Magazine’s parent company Media MICE Pte Ltd was the official media partner of the APAO 2018 congress held earlier this year in Hong Kong.
PIE (Posterior Segment - Innovation - Enlightenment) is Asia-Pacific's First Magazine On The Posterior Segment. PIE Magazine is published by...
Published on Dec 17, 2018
PIE (Posterior Segment - Innovation - Enlightenment) is Asia-Pacific's First Magazine On The Posterior Segment. PIE Magazine is published by...