THE WORLD’S FIRST FUNKY OPHTHALMOLOGY MAGAZINE
THE WILD WEST ISSUE March/April 2021 piemagazine.org
R ST VE
posterior posteriorsegment segment••innovation innovation••enlightenment enlightenment
OZURDEX® acts fast1,2 and lasts3–5 with less treatment visits compared with anti-VEGFs,5 making it the enduring partner you need. Effective DME treatment doesn’t have to be a burden.6
The most commonly reported adverse events reported following treatment with OZURDEX® are those frequently observed with ophthalmic steroid treatment or intravitreal injections (elevated IOP, cataract formation and conjunctival or vitreal haemorrhage respectively). Less frequently reported, but more serious, adverse reactions include endophthalmitis, necrotizing retinitis, retinal detachment and retinal tear. Licences may vary by country, please refer to your local country SmPC. DME, diabetic macular edema; IOP, intraocular pressure; VEGF, vascular endothelial growth factor. 1. Lo Giudice G et al. Eur J Ophthalmol 2018;28(1):74–79. 2. Veritti D et al. Ophthalmologica 2017;238(1–2):100–105. 3. Escobar-Barranco JJ et al. Ophthalmologica 2015;233(3–4):176–185. 4. Allergan. OZURDEX® Summary of Product Characteristics. 5. Kodjikian L et al. Biomed Res Int 2018:8289253. 6. Boyer DS et al. Ophthalmology 2014;121:(10):1904–1914.
INDICATIONS & USAGE: OZURDEX® contains a corticosteroid indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO), for the treatment of non-infectious uveitis affecting the posterior segment of the eye, and for the treatment of patients with visual impairment due to diabetic macular edema (DME) who are pseudophakic or who are considered insufficiently responsive to, or unsuitable for non-corticosteroid therapy. DOSAGE & ADMINISTRATION: For ophthalmic intravitreal injection only. The intravitreal injection procedure should be carried out under controlled aseptic conditions. Following the intravitreal injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. DOSAGE FORMS & STRENGTHS: Intravitreal implant containing dexamethasone 0.7 mg in the NOVADUR™ solid polymer drug delivery system. CONTRAINDICATIONS: Ocular or periocular infections. Advanced glaucoma. Aphakic eyes with ruptured posterior lens capsule. Eyes with ACIOL, iris or transscleral fixated IOLs and rupture of the
posterior lens capsule. Hypersensitivity. WARNINGS AND PRECAUTIONS: Intravitreal injections have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, retinal detachments, and implant migration into the anterior chamber. Patients should be monitored following the injection. Patients who has a tear in the posterior lens capsule (e.g., due to cataract surgery), or who had an iris opening to the vitreous cavity (e.g., due to iridectomy) are at risk of implant migration into the anterior chamber. Use of corticosteroids may produce posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and may enhance establishment of secondary ocular infections due to bacteria, fungi, or virus. Corticosteroids should be used cautiously in patients with a history of ocular herpes simplex. ADVERSE REACTIONS: In controlled studies, the most common adverse reactions reported by 20–70% of patients were cataract, increased intraocular pressure and conjunctival haemorrhage.
Licenses may vary by country, please consult your local Summary of Product Characteristics. Adverse events should be reported to your Ministry of Health and local Allergan office. JOB CODE: INT-OZU-2050218 DATE OF PREPARATION: NOVEMBER 2020
OZURDEX® is not licensed for use in DME in China.
IN THIS ISSUE...
Posterior Segment magazine posterior segment • innovation • enlightenment
Matt Young CEO & Publisher
08 Floaters, Flickers and Flashes — Oh my! Let’s Review Treatments in Retinal Detachment
Diagnosis of PCV and AMD Continues to Puzzle Expert
Hannah Nguyen Production & Circulation Manager
Gloria D. Gamat
Brooke Herron Editor
International Business Development
Ruchi Mahajan Ranga Brandon Winkeler Writers
Andrew Sweeney April Ingram Chow Ee-Tan Elisa DeMartino Joanna Lee Hazlin Hassan Olawale Salami Sam McCommon Tan Sher Lynn
20 22 24
Luis Diaz-Santana Nikki Hafezi
Darn Near Magic: Curing Blindness with Implants and Chemically Induced Cells APTOS-APOIS Updates: At-Home Monitoring and Patient-Centered AI The Race for Success in Home Monitoring: Only Those with the Broadest Vision will Prevail
Maricel Salvador Graphic Designer
The Eclectic Approach to Becoming a CEO, Part 1
Webinar Reminds Ophthalmology about Retina Awesomeness
Real World Results Highlight Gene Therapy Success
Media MICE Pte. Ltd.
6001 Beach Road, #19-06 Golden Mile Tower, Singapore 199589 Tel: +65 8186 7677 / +1 302 261 5379 Email: firstname.lastname@example.org www.mediaMICE.com
Ophthalmic Business Performance Strong and Stable despite COVID-19
We are looking for eye docs who can contribute articles to PIE magazine. Interested? Let's talk! Send us an email at email@example.com. To place an advertisement, advertorial, symposium highlight, video, email blast, or other promotion in PIE magazine contact CEO Matt Young at firstname.lastname@example.org.
LETTER TO READERS
s d n a H C A P My Old A
just looked at the date and realized I left the United States to live and work abroad exactly 15 years ago, in April.
I had moved to China, and I remember when you hit 10 years living there, you could be called an “Old China Hand.” I’ve lived in China, Vietnam, Malaysia and Singapore, so I’m hoping the term “Old APAC Hand” will do. Anyways, my APAC anniversary is timely because this is a Double Issue, where we publish the magazine both during the ARVO conference in the West, and at our very own CAKE & PIE Expo (C&PE) in the East. Even 14 years into my journey, this level of East/West ophthalmic communication and integration wouldn’t have been possible. It took the full 15 to pull this level of APAC/global communication — and now our very own show — development off. Some serious globetrotting shoe leather made this happen, though now I guess more virtual shoe leather. And so it is. This has become my role in eye care life — to be a cross cultural eye care connector and amplifier from West to East, and from East to West. At this intersection, you would think there would be more people like me working to help make such connections happen. There aren’t. Recently I wondered why this is the case, and then recalled a LinkedIn recommendation I had received by my first employee, Isaac Zhang, who now directs his own successful business, SME Digital Marketing. “Matt is a seasoned entrepreneur making splashes in the Ophthalmology and Medical Editorial arena,” Isaac wrote. “His unique (and sometimes painful) experiences in sailing the high seas in both the East and the West makes him a reliable advisor of cross cultural relations on a global scale. Rarely does one encounter such a
creative spirit with the firm belief and perseverance in what he does and the value he brings.” Creativity. Perseverance. Pain. And High Seas. Creativity is fantastic, but it can be drudgery in combination with the other three. “Can be,” I say. But like Dr. Strangelove, I learned to stop worrying and love...well...if not the bomb, then the potential explosiveness of certain situations. Wearing a panther-patterned chef outfit or dressed as the super hero “PIE Person” while having serious conversations with top surgeons or C-suite executives in our field wasn’t a guaranteed success factor in my earlier days. But I figured that Lady Gaga wasn’t always Lady Gaga. There was a moment she obtained critical mass, and became the Lady she was always meant to be. After my so-called “Lost Years” in China, I crossed the border from Singapore to my new home of Johor Bahru, Malaysia, 12 years ago at night on a public bus. Arriving at my lodging, I remember the eerie quiet during the the first night. I didn’t have a network there, and so felt like a small spider dangling by a thread at the end of a broken web, alone in a dark void. I had no friend, either in Singapore or Malaysia. And I didn’t travel much for lack of funding and vision in those early days, except between the two. And yet, being an outsider, I would need to build up a network fast. The fastest way to do this, was by being noticed. And if you haven’t noticed, my trademark is that I figured out how to do that in our field. The outward success that I had with this kind of marketing and media was building an inner success of character development. Through my 30s, I was constantly plagued by self-doubt, anxiety, and overall insecurity.
| March/April 2021
While I entertained these weaknesses, it wasn’t in my nature to give into them. Quite the opposite. I attacked the aspects of my character I didn’t appreciate with metaphorical fire. I forced calm by having to make high level connections wearing ridiculous outfits. I forced confidence by making sale after sale, while still believing I was a terrible salesman (though less worse as time passed). The impediments were myself, and while trivial forms of escape are on tap for us humans, I had decided to provide more challenges that would necessitate a higher level of “overcoming.” To this day, most people in our field likely would not consider me among even minor intellects of our ophthalmic time. I’d agree with them. We may all be wrong. Regardless, there is an inner wisdom, and I do not know from where it came. But it runs thick, wide, deep and wry. And if you happen to make it to our CAKE & PIE Expo (C&PE), I hope you’ll find out more about this ophthalmic “Dao” so to speak, and the mystical adventure that can be ophthalmic life from East to West, and back again, whether literally or metaphorically, for all of us.
M at t Young
CEO & Publisher Media MICE, PIE, CAKE and COOKIE magazines.
Achieve unsurpassed and sustained visual acuity (VA) gains with proactive extended dosing1–5
EYLEA® is indicated for adults for the treatment of neovascular (wet) age-related macular degeneration (AMD), visual impairment due to macular edema secondary to retinal vein occlusion (branch RVO or central RVO), visual impairment due to diabetic macular edema (DME), and visual impairment due to myopic choroidal neovascularization (myopic CNV).
REFERENCES: 1. EYLEA® approved package insert Singapore March 2019, Bayer (South East Asia) Pte Ltd. 2. Wells JA, Glassman AR, Ayala AR, et al. Aﬂibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology. 2016;123:1351-1359. 3. Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. Intravitreal aﬂibercept for diabetic macular edema. Ophthalmology. 2014;121:2247-2254. 4. Eleftheriadou M, Gemenetzi M, Lukic M, et al. Three-year outcomes of aﬂibercept treatment for neovascular age-related macular degeneration: evidence from a clinical setting. Ophthalmol Ther. 2018;7:361-368. 5. Pielen A, Clark WL, Boyer DS, et al. Integrated results from the COPERNICUS and GALILEO studies. Clin Ophthalmol. 2017;11:1533-1540.
Bayer (South East Asia) Pte Ltd 2, Tanjong Katong Road #07-01, Paya Lebar Quarter 3, Singapore 437161. Tel: +65 496 1888 Fax: +65 6496 1491 Website: www.bayer.com
| March/April 2021
ABBREVIATED PRESCRIBING INFORMATION EYLEA SOLUTION FOR INJECTION IN VIAL 2MG. Approved name(s) of the active ingredient(s) One ml solution for injection contains 40 mg aﬂibercept. Each vial provides a usable amount to deliver a single dose of 50 µl containing 2 mg aﬂibercept. Indication EYLEA is indicated for the treatment of neovascular (wet) age-related macular degeneration (AMD), macular edema secondary to retinal vein occlusion (branch RVO or central RVO), diabetic macular edema (DME) and myopic choroidal neovascularization (myopic CNV). Dosage Regimen wAMD: The recommended dose for EYLEA is 2 mg aﬂibercept, equivalent to 50 µl. EYLEA treatment is initiated with one injection per month for three consecutive doses, followed by one injection every two months. Based on the physician’s judgement of visual and/or anatomic outcomes, the treatment interval may be maintained at two months or further extended, such as with a treat-and-extend dosing regimen, where treatment intervals are increased in 2- or 4- weekly increments to maintain stable visual and/or anatomic outcomes. If visual and/or anatomic outcomes deteriorate, the treatment interval should be shortened accordingly to a minimum of two months during the ﬁrst 12 months of treatment. There is no requirement for monitoring between injections. Based on the physician’s judgement the schedule of monitoring visits may be more frequent than the injection visits. Treatment interval greater than 4 months between injections have not been studied. Branch RVO or central RVO: The recommended dose for EYLEA is 2 mg aﬂibercept, equivalent to 50 microliters. After the initial injection, treatment is given monthly until visual and/or anatomic outcomes are stable. Three or more consecutive, monthly injections may be needed. The interval between two doses should not be shorter than one month. If there is no improvement in visual and anatomic outcomes over the course of the ﬁrst three injections, continued treatment is not recommended. If necessary, treatment may be continued and the interval may be extended based on visual and/or anatomic outcomes (treat and extend regimen). Usually, monitoring should be done at the injection visits. During treatment interval extension through to completion of therapy, the monitoring schedule should be determined by the treating physician based on the individual patient’s response and may be more frequent than the schedule of injections. DME: The recommended dose for EYLEA is 2 mg aﬂibercept, equivalent to 50 microliters. EYLEA treatment is initiated with one injection per month for ﬁve consecutive doses followed by one injection every two months. There is no requirement for monitoring between injections. After the ﬁrst 12 months of treatment with EYLEA, and based on visual and/or anatomic outcomes, the treatment interval may be extended, such as with a treat-and-extend dosing regimen, where the treatment intervals are gradually increased to maintain stable visual and/or anatomic outcomes; however there are insufﬁcient data to conclude on the length of these intervals. If visual and/or anatomic outcomes deteriorate, the treatment interval should be shortened accordingly. The schedule for monitoring should therefore be determined by the treating physician and may be more frequent than the schedule of injections. If visual and anatomic outcomes indicate that the patient is not beneﬁting from continued treatment, EYLEA should be discontinued. Myopic CNV: The recommended dose for EYLEA is a single intravitreal injection of 2 mg aﬂibercept, equivalent to 50 microliters. Additional doses should be administered only if visual and anatomic outcomes indicate that the disease persists. Recurrences are treated like a new manifestation of the disease. The monitoring schedule should be determined by the treating physician based on the individual patient’s response. The interval between two doses should not be shorter than one month. Method of administration Intravitreal injections must be carried out according to medical standards and applicable guidelines by a qualiﬁed physician experienced in administering intravitreal injections. Following intravitreal injection patients should be instructed to report any symptoms suggestive of endophthalmitis (e.g., eye pain, redness of the eye, photophobia, blurring of vision) without delay. Each vial should only be used for the treatment of a single eye. Contraindications Hypersensitivity to the active substance aﬂibercept or to any of the excipients, active or suspected ocular or periocular infection, active severe intraocular inﬂammation. Special warnings and special precautions for use Endophthalmitis, increase in intraocular pressure, immunogenicity, systemic adverse events including non-ocular haemorrhages and arterial thromboembolic events. As with other intravitreal anti-VEGF treatments for AMD, the safety and efﬁcacy of Eylea therapy administered to both eyes concurrently have not been systematically studied. When initiating Eylea therapy, caution should be used in patients with risk factors for retinal pigment epithelial tears. The dose should be withheld and treatment should not be resumed earlier than the next scheduled treatment in the event of: a decrease in best-corrected visual acuity (BCVA) of ≥30 letters compared with the last assessment of visual acuity; a subretinal haemorrhage involving the centre of the fovea, or, if the size of the haemorrhage is ≥50%, of the total lesion area. The dose should be withheld within the previous or next 28 days in the event of a performed or planned intraocular surgery. EYLEA should not be used in pregnancy unless the potential beneﬁt outweighs the potential risk to the foetus. Women of childbearing potential have to use effective contraception during treatment and for at least 3 months after the last injection of aﬂibercept. Undesirable effects Very Common: Conjunctival hemorrhage, eye pain. Common: Retinal pigment epithelial tear, detachment of the retinal pigment epithelium, retinal degeneration, vitreous haemorrhage, cataract (cortical, nuclear, subcapsular), corneal erosion, corneal abrasion, intraocular pressure increased, vision blurred, vitreous ﬂoaters or detachment, injection site pain, foreign body sensation in eyes, lacrimation increased, eyelid edema, injection site hemorrhage, punctate keratitis, conjunctival hyperemia, ocular hyperemia. For a full listing of precautions and undesirable effects, please refer to the full product insert. For further prescribing information, please contact: Bayer (South East Asia)Pte Ltd. 2 Tanjong Katong Road #07-01 Paya Lebar Quarter 3 Singapore 437161. Date of revision of text March 2019.
ADVISORY BOARD MEMBERS SOCIETY FRIENDS Prof. Gemmy Cheung, MBBS, FRCOphth (UK), FAMS, MCI, is currently a professor at Duke-NUS Medical School, National University of Singapore, and head of the Medical Retina Department at Singapore National Eye Center (SNEC). Her research focuses on retinal diseases, including age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV) and myopic macular degeneration, as well as risk factors for these conditions that may be unique to Asian populations. Prof. Cheung has more than 200 peer-reviewed publications and serves on the editorial boards of several journals, including the American Journal of Ophthalmology, Retina and Eye. Prof. Gemmy Cheung
Prof. Mark Gillies
Prof. Mark Gillies, MBBS, PhD, FRANZCO, 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. Prof. 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 — among other treatments and studies. Prof. Gillies is a dedicated and multi-awarded researcher. email@example.com
Prof. Dr. Vishali Gupta
Prof. Dr. Vishali Gupta, MD, is an accomplished vitreo-retina and uvea expert of international repute. She currently works as a professor of ophthalmology at Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 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 vitreoretinal and uveitis diseases. Prof. Gupta also holds a U.S. patent for the development of multiplex PCR for uveitis. In addition, she is a sought-after speaker and has delivered more than 870 invited lectures and conducted sev eral instruction courses at various international and national meetings. She has more than 200 publications in peer-reviewed journals; has edited five books and contributed 72 book chapters in textbooks. She is the secretary of the International Uveitis Study Group, and member of the AAO, Club Jules Gonin and the Macula Society. She is currently the president of the Uveitis Society of India. Prof. Gupta has received several awards for her work, including the first JN Pahwa award from the Vitreo-Retinal Society of India (VRSI), the first NA Rao Award from the Uveitis Society of India, and the first NA Rao award from All India Ophthalmological Society (AIOS). firstname.lastname@example.org
All India Ophthalmological Society
| March/April 2021
Asia-Pacific Vitreo-retina Society
Vitreo-Retinal Society India
Ophthalmology Innovation Summit
He Eye Specialist Hospital
Subthreshold Ophthalmic Laser Society
Asean Ophthalmology Society
| March/April 2021
Floaters, Flickers and Flashes — Oh my! Let’s Review Treatments in Retinal Detachment by Elisa DeMartino
prevents complications and has a 90% success rate.²
Inverted vitrectomy Dr. Hudson Nakamura, is an ophthalmologist at the Eye Bank Foundation of Goiás, Goiânia, Brazil, with some 25 years of experience. He devised his own unique version of this surgery. Many people are familiar with Brazilians’ cool football tricks, but this doctor has a cool trick with eyes!
ictured above is an extreme example of a detached retina.
Kidding, of course. Human retinas obviously don’t detach quite to that extent and are considerably more complicated fix than just a needle and thread. In fact, PIE interviewed two vitrectomy experts from across the world to delve into just how intricate treatment for retinal detachment is underneath the surface. Before we hear from them, let’s briefly look at the fundamentals. There are three main types of retinal detachment: Rhegmatogenous, the most common, for which the primary cause is the vitreous separating from the retina due to aging; tractional, in which poorly maintained diabetes causes scar tissue to separate the retina from the back of the eye; and exudative, where fluid accumulates beneath the retina as a result of trauma or age-related macular degeneration.¹
More rarely, retinal detachment can be caused by other conditions. According to the American Academy of Ophthalmology (AAO), a detached retina can be caused by inflammatory conditions such as uveitis and retinal necrosis, as well as Vogt-KoyanagiHarada disease, the latter of which is more common in Asia for genetic reasons. Signs of retinal detachment begin with the patient seeing floaters or flashes in their vision. Naturally, with different problems come different solutions. The most common surgical treatment for a detached retina is vitrectomy, during which vitreous humor gel is removed for better access to the retina and then replaced with saline, a gas bubble, or silicone oil. Vitrectomy is a straightforward procedure for both complicated and uncomplicated, albeit serious, retinal detachments. Other reasons for the vitrectomy’s prevalence are that it
| March/April 2021
“I don’t know anybody that performs inverted vitrectomy. I am probably the only one in the world.” You might ask: What’s an inverted vitrectomy? It’s exactly what it sounds like! “Everybody starts the surgery and they have in the microscope a small piece that is called the inverter. The lens inverts the image … I don’t need this piece. That’s why I call it inverted vitrectomy.” Dr. Nakamura posts heaps of fascinating videos to the YouTube channel Retinawesome Retina and Vitreous International and to EyeTube to demonstrate his surgical method. “People get crazy when they follow me,” he said. “‘How can you operate without the inverted image?’ Because I learned it. My brain just learned to do the surgery that way.” It’s worth noting that Dr. Nakamura prefers a wide-angle contact system over the popular non-contact alternative.
Pneumatic retinopexy and scleral buckling After vitrectomies, the next common surgery is pneumatic retinopexy, a minimally invasive procedure during which a gas bubble is injected into the
vitreous cavity to push the retina into position. It’s ideal for retinal breaks or tears but can also be applied in retinal detachment. While a 90% success rate can be achieved if conditions are optimal, this method is not as common as a vitrectomy for a number of reasons: It’s argued that it doesn’t relieve vitreoretinal traction in aged eyes; it requires more preoperative attention to locate retinal breaks; and the postoperative requirement of the patient to hold their head in position for a week is, frankly, not always realistic!³ Scleral buckling, our third option, is pretty much what it sounds like. A belt, usually of silicone, encircles the eye and relieves the force of the vitreous tugging on the retina. By itself this procedure will be permanent, but if used in conjunction with another surgery the buckle may be removed later on. Combined surgical methods of treatment are common. Cryopexy or laser surgery are often paired with pneumatic retinopexy or scleral buckling, for instance, to create scarring that holds the retina in place. The two on their own are really only applied to retinal tears, however.
Combination treatment Dr. Manish Nagpal, a vitreoretinal ophthalmologist with over 30,000 surgeries under his belt (or should we say “scleral buckle?”) describes an interesting way to combine surgical methods in his practice. Scleral buckling, he offers, is being given up to a larger extent because it doesn’t keep up with modernizing practices. However, he prefers them for young people with indications of a localized detachment with only one break. “We do external repair, we don’t go in and do a vitrectomy. What we’ve done is that we‘ve tried to use both together. We use vitrectomy visualizing systems to view inside but then we do buckling surgery from outside,” Dr. Nagpal explained. “Then we get the advantage of both. The buckling surgery is good for young people because vitrectomy can lead to early cataract formation and has its own complications.” Dr. Nagpal explained that selecting this
or an alternative treatment varies with the type of break they see, alluding to small tears, small holes, giant tears or lattice degeneration with breaks. Still, he reports that 95% of his cases call for vitrectomies.
The “downside” to silicone oil Dr. Nagpal has authored an expansive list of publications, but one complication source stands out among them: silicone oil-based surgeries. “We’ve looked at how silicone oil affects the vision while it’s inside the eye, and when we remove it the quality of vision improves,” he explained. “It’s only causing a refractive error difference.” Past studies have also shown that particulate matter in the silicone oil can negatively affect vision while the oil is inside, but similarly, vision improves once the oil was removed and those particles went away. He also discussed the possibility of redetachment in silicone oil-based surgeries. “At times when we remove oil there is a small group of patients who re-detach.” Dr. Nagpal describes everything with detailed clarity. “So, we’ve looked at factors which reduce the chances of redetachment post-oil … in the primary surgeries before putting oil, if you do a 360 barrage laser and remove the oil after 3 months, 6 months, the chances of reattaching are much less as opposed to those who don’t have a 360 barrage done on them in the primary surgery.” Using a belt buckle with silicone oil also results in less chances of redetachment. Are your eyes greedy for more material on detachment complications? These doctors are, too: interesting cases fuel them. “Regular detachments and all are fun, but what I particularly like is complex cases … we get a lot of detachments which are already operated on, when there’s a failure the patient comes to us and we reoperate.” Dr. Nagpal smiles fondly, saying “and those are the challenges I love.”
detachments with proliferative vitreoretinopathy, complicated retinal detachments with epiretinal membranes, complicated retinal detachments together with macular holes,” our inverted vitrectomy expert Dr. Nakamura relates. “Of all this stuff I have videos to show.” We recommend the videos too!
Retinal Detachment - Symptoms and Causes.
Mayo Clinic Website. Available here: https:// www.mayoclinic.org/diseases-conditions/retinaldetachment/symptoms-causes/syc-20351344 Accessed on March 17, 2021.
Vitrectomy. The American Society of Retinal Specialists (ASRS) Website. Available here: https://www.asrs.org/patients/retinal-diseases/25/ vitrectomy Accessed on March 17, 2021.
Stewart S, Chan W. Pneumatic retinopexy: patient selection and specific factors. Clin Ophthalmol. 2018;12:493-502.
Contributing Doctors Dr. Hudson Nakamura is an ophthalmologist specializing in the retina and vitreous. He completed his medical degree from School of Medicine at the Federal University of Goiás, UFG and residency from the Base Hospital of the Federal District, Brasília, DF. Presently, Dr. Nakamura is a member of the AAO, Brazilian Council of Ophthalmology, Canadian Society of Ophthalmology and ARVO. He currently works as a professor in the Department of Retina and Vitreous Course of Medical Residency in Ophthalmology at the Bank of Goias Eye Foundation. Dr. Nakamura holds a vitreoretinal disease fellowship from the University of Toronto Canada and the Brazilian Center for Eye Surgery. email@example.com
Dr. Manish Nagpal is a vitreoretinal consultant at the RetinaFoundation in Ahmedabad, Gujarat, India. He has been recognized for his development and presentation of surgical videos and educating the ophthalmic community of advancements in information technology within the field firstname.lastname@example.org
“We see complicated retinal detachments, that means retinal
| March/April 2021
Diagnosis of PCV and AMD Continues to Puzzle Experts by Joanna Lee
iagnosing PCV and AMD can be a puzzling conundrum — even for experts. So, at the recently held All India Ophthalmological Society’s first International Ophthalmic Conclave (AIOS IOC 2021), the panel dove right in to discuss these challenges. A session on these two conditions kicked off with a look at Pachychoroid Disease — An Enigma, where Prof. Dr. Atul Kumar, professor from the R.P. Centre for Ophthalmic Sciences at All India Institute of Medical Sciences, New Delhi, introduced the features that define this group of macular diseases.¹ In an attempt to unravel this mystery, Prof. Dr. Kumar shared that the disease features manifest choroidal findings similar to a thickened choroid. “It’s unique as it has four entities within the pachychoroid clinical spectrum: pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), pachychoroid neovasculopathy (PNV), and polypoidal choroidal vasculopathy (PCV),” he said. Pachychoroid disease (or choroidal venous insufficiency) is characterized by a loss of inner choroid, dilated choroidal veins or “pachyvessels,” which Prof. Dr. Kumar described as “a congestion of the vessels” that contributes to the focal increase in choroidal thickness and drusenoid deposits (pachydrusens). He said the vessels also leak dye on ICGA
from the EVEREST study and the Central Reading Center’s grading of the confocal scanning laser ophthalmoscope (cSLO)based ICGA — there are other roads that lead to PCV diagnosis. Dr. Timothy Lai from the Department of Ophthalmology and Visual Sciences at The Chinese University of Hong Kong, spoke about several non-ICGA methods doctors can utilize. One such is the fundus appearance of PCV in the OCT characterized by notched or hemorrhagic PEDs²; while on SD-OCT, doctors should look out for PED notches, sharply peaked PED or hyperreflexive rings.³ Since PCV involves an abnormal choroidal layer with neovascularization, enhanced depth imaging (EDI) OCT is also useful for visualizing and assessing these choroidal layers. Besides that, en face OCT can also be used to visualize pachyvessels and RPE elevation. As a result of an international working committee to identify nonICGA features for PCV, Dr. Lai and his team published a paper⁴ in 2020 detailing their discovery of nine non-ICGA features that might be useful for the predictive value of PCV diagnosis.
(indocyanine green angiography), while sharing his preference for using Topcon’s (Tokyo, Japan) SS-OCT and OCT-A for diagnoses. “Many CSC patients have early neovessel membranes. I feel this disease has so much overlap so you can’t ignore a patient with CSC, especially once they’ve crossed three or four months,” added Prof. Dr. Kumar.
New insights into alterations of PCV and CSC choroidal perfusion
Non-ICGA diagnostic criteria for PCV
In an attempt to find out what actually leads to the “choroidal congestions,” mentioned earlier by Prof. Dr. Kumar, Dr. Gemmy Cheung from the Singapore National Eye Centre (SNEC) highlighted a few recent studies that could potentially shed light on the causes of the congestion, and perhaps open up new perspectives in the study of PCV.
Although ICGA remains the gold standard for polypoidal choroidal vasculopathy (PCV) diagnosis — based on the most common diagnostic criteria
With the commonly agreed hypothesis that the choroid is the location of CSC, doctors are now using the thickness of the choroid based on OCT findings
| March/April 2021
together with IGCA, to show vascular hyperpermeability for diagnosis.
including one on using AI for detecting PCV without ICGA.¹¹
“Looking at choroidal hyperpermeability, could a choroidal outflow disturbance be a cause instead?” asked Dr. Cheung. For dilated Haller’s vessels, she hypothesized that intervortex anastomotic vessels⁵ could be one of the parameters of the condition; whereas for increased thickness, it could be due to venous stasis and leakage. Perhaps by studying the choroidal vasculature index (CVI)⁶, it may add further understanding to the functional changes within the choroid, she said, after showing that CVI would increase as the choroidal thickness decreases. This is probably due to the persistence of dilated vessel lumen (the anastomosis) and a reduction in stromal congestion or hyperpermeability.
“Most of the studies report good results with the AUC (area under the curve) around 90% for detection and 70% for prediction,” he said, noting that most of the studies using AI for CFP used datasets from AREDS, containing validation within the AREDS and with no validation in new datasets.
Is AI’s application in PCV and AMD limited for now? The discussion also looked at artificial intelligence (AI) with Dr. Paisan Ruamviboonsuk from the Department of Ophthalmology, Rajavithi Hospital in Bangkok, Thailand, presenting several studies, such as those that have used deep learning to determine characteristics of age-related macular degeneration (AMD)⁷, to detect geographic atrophy (GA)⁸, to detect pseudodrusens from fundus autofluorescence (FAF) or color fundus photography (CFP)⁹, and AI for OCT images in AMD.¹⁰ Dr. Paisan also presented other studies,
“While most of the results published in these AI studies are good, I think it’s going to take a while in terms of applying them in the real world,” said Dr. Ruamviboonsuk. The panel then ruminated on the sustainability of doctors’ roles in the light of emerging AI technology. “AI will have a role for primary care physicians who can transport the images and study them,” Prof. Dr. Kumar said.
Chang from the Retinal Unit at Sydney Eye Hospital and Sydney Retina Clinic at Sydney University, Australia, spoke on Submacular Hemorrhage Polypoidal Vasculopathy. He shared that subretinal bleeding may cause devastating vision loss. During the session, Dr. Chang also discussed the use of intravitreal gas injections as his first line treatment to pneumatically displace blood. “Vitrectomy is used in very selected cases, and while heavy liquid is useful as an adjunct with peripheral retinotomy being used as one needs to drain the blood peripherally, or if there’s exudative detachment that requires drainage as well,” he explained. While all these are his arsenal of therapies, Dr. Chang, like many doctors on this panel, still uses a combination of anti-VEGF and PDT as ongoing treatments.
Dr. Mangat Dogra chimed in: “It appears that AI will be a big thing in diagnosis. Maybe we will get to treat patients earlier and our role will still be found more in the treatment of patients.” The co-chair of this session Dr. Anand Rajendran added, “AI also appears to be pushing the direction of medicine into what it should be, toward preventive care rather than reactive care.”
Subretinal bleeding, surgical perspectives
Editor’s Note: The AIOS IOC 2021 was held on February 19 to 21. Reporting for this story took place during the event.
Lastly, the vitreoretinal perspective came into the equation when Dr. Andrew
References: Cheung CMG, Lee WK, Koizumi H, Dansingani K, Lai TYY, Freund KB. Pachychoroid disease. Eye (Lond). 2019 ;33(1):14-33.
Chaikitmongkol V,Kong J, Khunsongkiet P, et al. Sensitivity and Specificity of Potential Diagnostic Features Detected Using Fundus Photography, Optical Coherence Tomography, and Fluorescein Angiography for Polypoidal Choroidal Vasculopathy. JAMA Ophthalmol. 2019;137(6):661-667.
Gomi F, Tano Y. Polypoidal choroidal vasculopathy and treatments. Curr Opin Ophthalmol. 2008 ;19(3):208-212.
Cheung CMG,Lai TYY, Teo K, et al. Polypoidal Choroidal Vasculopathy: Consensus Nomenclature and Non-Indocyanine Green Angiograph Diagnostic Criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup. Ophthalmology. 2021;128(3):443-452.
Spaide RF, Ledesma-Gil G, Cheung CMG. Intervortex Venous Anastomosis in Pachychoroid-Related Disorders. Retina. 2020. Epub ahead of print.
Tan K-A, Agrawal R. Luminal and Stromal Areas of Choroid Determined by Binarization Method of Optical Coherence Tomographic Images. Am J Ophthalmol. 2015;160(2):394.
Burlina PM, Joshi N, Pacheco KD, Freund DE, Kong J, Bressler NM. Use of Deep Learning for Detailed Severity Characterization and Estimation of 5-Year Risk Among Patients With Age-Related Macular Degeneration. JAMA Ophthalmol. 2018;136(12):1359-1366.
Keenan TD, Dharssi S, Peng Y, et al. A Deep Learning Approach for Automated Detection of Geographic Atrophy from Color Fundus Photographs. Ophthalmology. 2019;126(11):1533-1540.
Keenan TDL, Chen Q, Peng Y, et al. Deep Learning Automated Detection of Reticular Pseudodrusen from Fundus Autofluorescence Images or Color Fundus Photographs in AREDS2. Ophthalmology. 2020;127(12):1674-1687.
Prahs P, Radeck V, Mayer C, et al. OCT-based deep learning algorithm for the evaluation of treatment indication with anti-vascular endothelial growth factor medications. Graefes Arch Clin Exp Ophthalmol. 2018;256(1):91-98.
Xu Z, Wang W, Yang J, et al. Automated diagnoses of age-related macular degeneration and polypoidal choroidal vasculopathy using bi-modal deep convolutional neural networks. Br J Ophthalmol. 2020;bjophthalmol-2020-315817.
| March/April 2021
y d d Vi
In vitreoretina practice, there was also a time when things were, let’s just say it — wild. For example, until medical retina rode onto the scene, doctors’ hands were tied (similar to the aforementioned damsels) with regard to treating diseases like age-related macular degeneration (AMD), diabetic retinopathy (DR) and diabetic macular edema (DME). Indeed, new pharmaceuticals, as well as innovations in surgical techniques and diagnostics, have helped tame this particular frontier. This “Gold Rush” changed treatment paradigms — and spurred some of ophthalmology’s greatest “duels” as doctors took aim at the target of improved outcomes. And the ophthalmic gold rush isn’t over yet. Certainly, newfound innovations have not only helped to conquer previous frontiers… they will help uncover new ones. So, strap a saddle onto that metaphorical horse and grab the reins — we’re ridin’ into the “Wild West” of vitreoretinal practice. (Yee-haw!)
owboys, duels, swinging-door saloons and damsels in distress (often, and inexplicably) tied to railroads… these are the tales of the Wild West as told by Hollywood — even though history does paint a somewhat tamer version.
by Brooke Herron
Wild W e th reoreti e
Mapping the frontier in vitreoretina During the Wild West, the frontier was the boundary between the known and unknown, the civilized and the untamed. In ophthalmology, there is a similar frontier — the before and after of practicechanging medical therapies, surgical techniques, imaging devices and diagnostic equipment. And when compared to the specialty’s history, these trails were only recently blazed...
Medical retina’s “ace-in-thehole” On frontier-changing innovations in medical retina, the response was unanimous: anti-VEGF is (and was) the ace-in-the-hole.
| March/April 2021
“Definitely, the development of antiVEGF drugs for the management of neovascular macular degeneration (nAMD) and diabetic macular edema changed posterior segment practice forever,” said Professor Anat Loewenstein from Tel Aviv University and the Tel Aviv Medical Center, Israel.
Dr. Judy Kim, from The Eye Institute at the Medical College of Wisconsin, Milwaukee, USA, agreed: “In the realm of medical retina, there is no question: antiVEGF. These intravitreal agents have not only stabilized, but also improved vision, in patients with various retinal-vascular diseases.”
result would be better compared to no treatment years down the line. “I remember getting a sick feeling in my stomach after treating a patient with subfoveal CNV with laser, knowing well that her vision would be worse the next day, and wondering if this is the best we can do for these patients.”
City and The American Eye Center, Philippines. “Pars plana vitrectomy has allowed us to manage more and more cases — from the simplest vitreous hemorrhage to complicated retinal detachment surgery, to the most delicate ILM (internal limiting membrane) peeling.”
This was echoed by Dr. Vaibhav Sethi in India, as well as Dr. Andrew Chang in Australia, who added that anti-VEGF is not only a sight-saving therapy for conditions like nAMD, DME and RVO (retinal vein occlusion), its development has led to a paradigm shift.
Dr. Kim continued: “I am old enough to have done submacular surgery to remove CNV, as well as limited macular translocation to move the fovea away from the CNV — and, don’t forget radiation treatment for wet AMD. Now those were truly the wild, wild times!”
“Without PPV as a surgical modality, many eyes would still be going blind,” added Dr. Kim. “Since its development, much has changed over the years, such as the cut speed, improved fluidics, and smaller gauge instruments. However, these are all tweaks to the fundamental system.”
Before anti-VEGF reared its “vascular endothelial growth factor-head,” the only available treatments were thermal laser and PDT, neither of which were necessarily ideal. This is because thermal laser is destructive to neural tissue with resulting loss of vision and scotoma — and there’s a high recurrence rate. Meanwhile, PDT is not very effective in improving vision and needs repeat treatment,” explained Dr. Chang from Sydney Retina Clinic and Sydney Eye Hospital.
These insights beg the question: Back then, what was worse: the disease or the treatment?
To add to laser’s woes, using it for macular degeneration was only proven effective in decreasing loss of vision in very specific lesions; later, PDT gave stabilization of vision, but only in a subset of patients, said Prof. Loewenstein. “And for diabetic macular edema, we only had laser which was not beneficial enough.” Dr. Kim also had a yarn on laser: “Prior to anti-VEGF, laser was the treatment of choice for DME, PDR and macular edema from branch retinal vein occlusion (BRVO) — even thermal laser was used at one time for wet AMD based on the Macular Photocoagulation Study.” She explained that they used to draw out the location of the choroidal neovascular membrane (CNV) based on fluorescein angiogram and then treat with laser. Using this procedure, Dr. Kim said: “Juxtafoveal CNV patients may do well, albeit with paracentral scotoma, as long as there is no enlargement of the laser scar over time.” However, those with subfoveal lesions experienced an immediate decline in vision — with the hope that this
Thankfully, when anti-VEGF entered the scene, it changed everything. “We moved from a situation where everyone lost vision, to a situation where (almost) no one loses vision and has stable vision for a long time,” said Prof. Loewenstein. That’s like going from a lame horse to a steam locomotive — full speed ahead. However, like the railroad in its expansion of the west, anti-VEGF has also encountered some challenges. While these hurdles aren’t masked bandits with explosives, they can still cause derailments. “There are new challenges in patient compliance and the burden associated with intensive treatment regimes,” shared Dr. Chang. “Clinics, physicians and stakeholders have had to adapt workflows to manage this.” These “derailments” will hopefully be managed with drugs with longer durability and port delivery systems, which are on the horizon, he added.
Frontiers evolve in surgical retina
According to Dr. Chang, one of these “tweaks” was the procedure’s evolution to transconjunctival sutureless vitrectomy (TSV) which is more surgically efficient, improves patient outcomes and allows for a more rapid recovery. “This technology has paralleled improvements in cutter and instrumentation technology… higher speed cutters, smaller gauge instruments, brighter and safer light sources, improved visualization with microscope viewing systems including 3D vitrectomy (i.e., NGENUITY 3D Visualization, Alcon, Geneva, Switzerland; and ZEISS ARTEVO 800, Carl Zeiss Meditec, Jena, Germany) and intraoperative OCT,” said Dr. Chang. He continued: “Prior to this, we had conjunctival peritomy, which required suturing, larger gauge instrumentation and had higher risk of complications, including retina and vitreous incarceration. Plus, older visualization techniques provided less surgical control.”
Of course, not all conditions can be placated with the “magic bullet” of an anti-VEGF injection — some will inevitably require surgical management. Thus, the surgical frontier is in flux as new techniques evolve.
Another pre-vitrectomy procedure was scleral buckling, added Dr. Kim. However, this procedure is limited in usage, as many eyes cannot be fixed with scleral buckling alone.
A big shift occurred with the introduction and evolution of pars plana vitrectomy (PPV), shared Dr. Sherman Valero from The Makati Medical Center, The Medical
In addition to vitrectomy, the development of perfluorocarbon (PFC) liquid has also been crucial to increased success in complex
| March/April 2021
cases. “Prior to this development, the surgical bed was turned upside down and air was used intraoperatively to flatten the retina and surgeons worked from below! Imagine the neck and back pain for the surgeons and the assistants!” shared Dr. Kim, adding that innovation in tamponading agents, such as various intraocular gases and silicone have also contributed greatly. Dr. Sethi from Arunodaya Deseret Eye Hospital, Gurugram, and Dr. Sethi’s Eye Centre, Delhi, India, said that wide angle viewing systems have forever impacted the way surgeons operate in the posterior segment. “This has changed the way we treat vitreoretinal disorders, both medically and surgically,” he explained, adding that previous treatments resulted in variable outcomes and associated collateral damage, like field of vision loss.
Can’t fix what you can’t see Further, enhancements in imaging have helped to lift the proverbial blindfold in vitreoretinal practice. “OCT (optical coherence tomography) has changed the way we practice retina — allowing us to visualize, diagnose, manage and follow-up on retinal diseases to a degree that was unimaginable before,” Dr. Valero pointed out. Dr. Kim agreed. She shared that in her lifetime, along with anti-VEGF, OCT has revolutionized how retina patients are treated. This was echoed by Prof. Loewenstein. She explained that prior to OCT, there was only fluorescein angiography, which showed the retina in a much lower detail than OCT. “So, from the diagnostic point of view, definitely it was OCT that changed our lives forever — now, we’re able to see the retina extremely meticulously with great detail.”
Great duels in vitreoretina Bang, bang… we’ve got a stand-off. Like in the great duels of the Wild West, we asked our cutter-wielding surgeons to take 10 steps and shoot… their recommendations for treating diabetic retinopathy and retinal detachment, that
is. Will anti-VEGF hit first? Will laser find some footing? And how does the feud between scleral buckling and vitrectomy end?
Duel #1: AntiVEGF vs. laser in diabetic retinopathy In the duel between laser and anti-VEGF for DR, it was more of a tip-ofthe-hat and a handshake than a duel — in fact, most of the interviewed cowboys and cowgirls (of the doctor variety) agreed on the first-line treatment. Shots (not) fired! For DR patients, Dr. Valero said that before any treatment considerations, he begins with a discussion about the need for better sugar control and regular follow-up. Dr. Kim also takes this route: “If the patient has less than PDR and no DME, I monitor and educate on the importance of glycemic control and follow-up at various intervals, depending on the DR stage.”
PRP and PRP-anti-VEGF combos lead in PDR In cases of PDR without DME, or eyes with PDR and DME that achieve resolution of DME, Dr. Kim addresses the risks, benefits and alternatives of pan retinal photocoagulation (PRP) versus anti-VEGF therapy, and then together with the patient, the most appropriate treatment is determined. “Often, in a compliant patient, we start with anti-VEGF injections followed by PRP for extending the durability of treatment and reducing the treatment burden,” she said, noting that in DRCR Retina Network Protocol S, there was less difference in visual field loss between PRP treated eyes and antiVEGF-treated eyes at five years than at two years — and further, continuous anti-VEGF treatment for more than five years is a huge treatment burden. “I worry about patients getting sick and missing treatment visits along the way — and some patients worry about the copay at each visit. Therefore, minimizing the number of visits while maximizing the care is the goal.”
| March/April 2021
In her patients with PDR, Dr. Loewenstein said she also uses both PRP and anti-VEGF, depending on the patient: “I recommend either PRP or monthly injections, provided that the patient commits to being followed-up and treated monthly for a few months.” For patients with clinically significant disease like PDR, Dr. Valero said he usually offers PRP as the first-line treatment. “In the very few patients for whom the side effects of PRP are unacceptable, I offer anti-VEGF injections — but only after an exhaustive conversation about possible adverse events, the need for very regular treatment and follow-up, and the possibility of recurrence,” he said. This is because if PDR patients treated solely with anti-VEGF interrupt their treatment, they are at a high risk of developing irreversible blindness* — and that’s a gamble many aren’t willing to take. “I find that when anti-VEGF treatments are discontinued, neovascularization often recurs. This does not happen as often after good PRP,” explained Dr. Kim. She said that if the patient seems likes they will not follow up with recommended visits (e.g., due to health or transportation issues, in young patients with a history of noncompliance in diabetic care, or those already monocular from poor eye care, etc.) she will recommend PRP on the same day of the visit — not only for eyes with PDR but also with severe NPDR (nonproliferative diabetic retinopathy). “If at all possible, I do not want to lose the opportunity to treat and stabilize.” Dr. Chang also recommended laser for non-center involving PDR, as well as DME: “This is an effective therapy which requires less rigorous intervention in the long-term,” he explained. This rigorous intervention, like the treatment burden of monthly injections, was also noted by Dr. Sethi as a reason to treat PDR with PRP. “I prefer to treat PDR with PRP as most patients I come across are from far away places and cannot afford to get monthly anti-VEGF injections,” he explained. “If the patient is educated, willing to attend monthly follow-ups and can afford it, then I would advise anti-VEGF therapy for PDR — and only in cases
that don’t have significant traction or fibrovascular proliferation,” continued Dr. Sethi. In severe cases, he would also consider early vitrectomy, “as the visual outcome tends to get worse as we delay the surgical intervention.”
Anti-VEGF wins in DME What about DME? Here, anti-VEGF was the clear winner: When treated intensively with anti-VEGF drugs, about one-third of eyes with DME experience an improvement in their DR severity scale.1 However, steroids were also considered in some instances. “First-line treatment for diabetic macular edema? That would be an intravitreal anti-VEGF injection,” said Dr. Sethi. In patients with any DR and DME, Dr. Kim also begins anti-VEGF therapy — usually with Avastin (bevacizumab; Genentech, California, USA) as the drug costs less than other agents, and insurance pre-authorization is usually not necessary. “However, if the baseline visual acuity is less than 20/50 and/or there is significant central subfield thickness on OCT, I will switch to Eylea (aflibercept; Regeneron Pharmaceuticals, New York, USA) early based on DRCR Retina Network Protocol T findings,” explained Dr. Kim. In the Philippines, Dr. Valero also said anti-VEGF is his first line treatment, although the choice of which agent to use is cost-dependent, as he uses a self-pay system. For patients with recent cardiovascular or cerebrovascular events, as well as for those who have difficulty making monthly injection appointments, he would instead offer a steroid implant. In cases of DR with DME, Dr. Loewenstein also prefers anti-VEGF — this is because it’s shown to provide the best results. “In Israel we are obliged to start with bevacizumab. If after three injections there is not a good enough response, I switch to either ranibizumab or aflibercept,” she explained. Like Dr. Valero, Dr. Loewenstein would only deviate from using anti-VEGF if the patient could not commit to multiple visits and injections, or if there was a history of stroke or heart attack. “In these cases, I sometimes start with steroids as the first line treatment.”
Dr. Chang added: “Anti-VEGF therapy has revolutionized treatment of centerinvolving DME — it’s established and proven effective to restore and maintain sight.” However, he said that this comes with challenges of a demanding treatment regime and often, DME patients are working to support themselves and their families, and therefore could miss appointments. Plus, diabetic patients frequently suffer from related complications and see multiple doctors for diabetes and diabetes-associated conditions, he explained.
Duel #2: Vitrectomy vs. scleral buckle in retinal detachment Our second duel puts scleral buckle against vitrectomy to correct retinal detachment (RD). In this stand-off, vitrectomy hit the target for most doctors — however, there is still room for scleral buckle and other techniques, in certain patients and detachments. “Vitrectomy approach to RD repair is increasingly trending as the first-line [treatment] compared to scleral buckle,” said Dr. Chang. “This has arisen from technology improvements in cutters, machines, illumination, instrumentation and visualization systems that allow safe and effective surgery. Patient postoperative recovery also is potentially improved following vitrectomy versus buckle.” According to Dr. Kim, PPV is also the first-line therapy for older patients with posterior vitreous detachment, pseudophakic patients, or patients with cataract who understand that cataract surgery may be needed following RD repair. “For those with significant cataract, we do a combined surgery of PPV with cataract extraction at the same time. Even for eyes with RD-associated with giant retinal tear, PPV alone has been successful,” she explained. “For a great majority of my patients, I usually offer a primary PPV with gas and laser,” said Dr. Valero. “The introduction of small gauge sutureless vitrectomy has somewhat skewed my
preference to this method — this likely because a vitrectomy affords me greater confidence in visualizing and treating all the breaks. “It also allows me to clean the vitreous as much as possible and manage any existing PVR (proliferative vitreoretinopathy) more definitively. When you combine this with the ease of the newer system, it makes for an attractive choice for management of RD,” said Dr. Valero, adding that he would also offer pneumatic retinopexy for those who met the criteria, as well as segmental buckle for younger patients. These recommendations from Dr. Valero were in line with Dr. Loewenstein’s approach: “In most cases, I do a vitrectomy as it’s the fastest and very safe. If it’s a young patient with a tear that is relatively anterior and phakic, I may recommend a scleral buckle — or I will recommend pneumatic retinopexy if it meets the criteria,” she shared. Pneumatic retinopexy is certainly an option for localized retinal detachment with superior retinal tear, agreed Dr. Kim, adding that “it requires understanding and the compliance of the patient who is willing to position.” “In a young, phakic patient with clear media who refuses pneumatic, or if the tear(s) are not amenable to pneumatic retinopexy (e.g., multiple tears, inferior tears, extensive lattice or atrophic holes, etc.), scleral buckling is my first-line treatment,” continued Dr. Kim. Dr. Chang recommends scleral buckle in RD without posterior vitreous detachment, such as in younger patients with atrophic holes causing the RD or in retinal dialysis. He also considers this approach in patients who may not be able to cooperate with care or posture postoperatively. Dr. Sethi would also prefer taking the alternative approach of scleral buckling in young patients who have a clear lens and treatable peripheral retinal breaks, or lesions with or without PVR changes. In other instances, he primarily manages RD with micro-incision vitreoretinal surgery (MIVS) using 23-, 25- or 27-gauge instrumentation as per the case. “In uncomplicated cases without
| March/April 2021
PVR, I prefer to leave gas in the eye as tamponade, preferable SF6 or C3F8,” said Dr. Sethi. “In cases of traumatic retinal detachment or in cases of RD with PVR, I use silicone oil as a tamponade agent.”
as DME, AMD, etc., it’s exciting to see development of drug delivery systems that will allow for a more sustained dosing and better compliance to these medications — and hopefully translating to better outcomes.”
And for more complicated detachments, Dr. Kim combines scleral buckling with PPV. “These include eyes with recurrent RD, proliferative vitreoretinopathy or trauma. While I usually use gas as a tamponading agent, in these more complex cases, silicone oil has come in handy, but does require another surgery to remove the oil.”
“Port delivery systems combined with home monitoring holds promise for less interventions and personalized care in the treatment of conditions such as neovascular AMD or DME,” agreed Dr. Chang. “In vitreoretinal surgery, intraoperative OCT and heads-up 3D vitrectomy will be increasingly adopted as the cost falls and the machines become smaller and more ergonomic. This is an important foundation for virtual and robotic surgeries in the future.”
The “Gold Rush” in innovation In the era of the Wild West, settlers were driven west for a variety of reasons. One of which was gold — as in “there’s gold in them hills.” Now, in ophthalmology, we aren’t necessarily seeking golden nuggets, but rather “golden” innovations. So, what will ophthalmology pan for next? According to Dr. Kim, the next “gold rush” will be decreasing the treatment burden, improving early detection, and finding treatments for currently untreatable diseases. For decreasing treatment burden, longer effective drug duration in a consistent manner for as many patients as possible will be needed: “This is currently being approached in several different ways, including various drug delivery methods and drug design. Gene therapy will play a big role here, with the possibility of long-term drug delivery,” said Dr. Kim. Dr. Valero added: “Now that we have seen the success of drugs to treat a variety of retinal conditions such
Along those lines, Prof. Loewenstein shared, “The next ‘gold rush’ in vitreoretina practice will be longer acting drugs or devices, home monitoring by home OCT, and the use of virtual reality in vitreoretinal surgery. “AI, of course, is touted to be the next big thing in ophthalmology,” she continued. “Hopefully it will allow us to predict disease progression and give us a chance to improve patient outcomes.” In addition to its ability to predict, AI could also help improve early disease detection by capturing fluid recurrence sooner via home monitoring — this could incorporate data evaluation using AI, which allows for more frequent and accurate monitoring, said Dr. Kim. However, current models need infrastructure, reimbursement, and patient self-motivation to be effective. That said, she believes that this type of monitoring will become more important with the rise of longer durability treatments. “To me, AI incorporation in diagnostics will be the next big thing as it will change the way we practice vitreoretina. It will improve the diagnostic accuracy many folds and will be able to pick out details that a human observer might miss or overlook,” said Dr. Sethi. “It will also help in defining the management protocol customized to the particular eye. This will help the clinician to take the right step at the right time to get the best outcome for the patient.”
| March/April 2021
Dr. Chang also concluded that AI will assist the clinician in individualizing patient care and predicting what treatment a patient may require. And one final wish? “I wish someone could design a compact, portable, widefield, inexpensive multimodal imaging system that captured great images. This could be used by the public with immediate AI interpretation to help screen more people around the world and to attack vision problems, such as diabetic retinopathy. Am I asking for too much?” [Editor’s Note: We don’t think that’s asking for too much at all… but we’re writers, not amazing device designers.]
Making the west less “wild” Thanks to these frontier-shifting therapies, surgical techniques, and other ophthalmic innovations, vitreoretinal practice is certainly looking less “wild” than it may have 20 years ago. In fact, the dust from what were once great duels for treatment preference seems to have settled… and perhaps will only reignite with further development in instrumentation and techniques. However, a number of untreatable conditions or conditions remain that need to be better managed, including dry AMD, central retinal artery occlusion (CRVO), and inherited retinal degeneration, said Dr. Kim. She predicts both dry and wet AMD will attract more research: “Developments in complement inhibitors and cell therapies are being investigated — and this is a wide open frontier for someone to conquer!” So, as we saddle up to ride off into the sunset, we’re left to ponder the next frontier — and gold rush — in vitreoretinal practice: the rise of technologies like AI, improvement to existing therapies and delivery systems, and more. Certainly, these will have a profound impact in ophthalmology and treatment paradigms. Yee-haw, indeed.
* Wu L, Acón D, Wu A, Wu M. Vascular endothelial growth factor inhibition and proliferative diabetic retinopathy, a changing treatment paradigm?. Taiwan J Ophthalmol. 2019;9(4):216-223.
Contributing Doctors Prof. Anat Loewenstein, MD, is a professor of ophthalmology, vice dean of the Faculty of Medicine, and Sidney Fox Chair of Ophthalmology at the Sackler Faculty of Medicine at the Tel Aviv University, and the chairman of the Division of Ophthalmology at the Tel Aviv Medical Center in Israel. She studied medicine at the Hebrew University in Jerusalem. Following that, she spent four years in the Israeli Navy, completed residency in the Department of Ophthalmology at the Tel Aviv Medical Center in Tel Aviv, and fellowship in retina vascular diseases and vitreoretina surgery unit at the Wilmer Institute, at Johns Hopkins University Hospital in Baltimore, Maryland. She also completed a Master of Health Administration degree at the Tel Aviv University Business School. Her main fields of interest include the investigation of drug administration and toxicity to the retina, early detection of macular degeneration and home monitoring of disease. She was the leader behind the development of a novel technology for early detection of macular degeneration, the development of automated technology for detection of retinal disease activity, and the development of augmented virtual reality to replace the operating microscope, as well as development of home OCT. She has published 400 papers in peer reviewed journals, and contributed multiple chapters to ophthalmology textbooks. Prof. Loewenstein also serves in multiple roles in the most prominent retina societies. She has received multiple international awards, including the “Rosenthal” award, and the Patz medal of the Macula Society, as well as the Michelson Award of the Macula Society, and the Silver Fellow Medal of ARVO. email@example.com Dr. Judy E. Kim, MD, is an internationally well-known vitreoretinal specialist, a professor of Ophthalmology
and Visual Sciences with tenure, a professor of the Graduate School of Biomedical Sciences, and director of Teleophthalmology and Research at the Medical College of Wisconsin (MCW). She is a graduate of the University of Chicago, Johns Hopkins University School of Medicine, and completed her ophthalmology residency at the Bascom Palmer Eye Institute of the University of Miami and vitreoretinal fellowship at MCW. She has held leadership positions in numerous committees of major ophthalmology organizations. She is currently on the board of AAO, ASRS, Macula Society, Diabetic Retinopathy Clinical Research Retina network (DRCR.net), and NAEVR/AEVR. Dr. Kim has received numerous awards and honors, especially for her clinical excellence, leadership, and service to organizations. She has published over 200 papers and given over 400 presentations, including over 150 invited national and international presentations and named lectures. She has been actively involved with numerous multicenter clinical trials and has served as a vice-chair of DRCR.net, in which she currently serves as a national study chair for Protocol AE. Jekim@mcw.edu Dr. Andrew Chang, MBBS (Hons) PhD FRANZCO, is an ophthalmologist and retinal specialist. He is head of ophthalmology and head of the Retinal Unit at the Sydney Eye Hospital, clinical associate professor at the University of Sydney and Medical Director of Sydney Retina Clinic. In international ophthalmology, he serves as the secretary general of the AsiaPacific Vitreoretinal Society (APVRS) and council member of the Asia Pacific Academy of Ophthalmology (APAO). Other professional roles include clinician advisor to the Department of Health Australia, board director of Royal Australian and New Zealand College of Ophthalmologists (RANZCO) and the Sydney Eye Hospital Foundation. He is the recipient of the Achievement Award and Distinguished
Service Award of the APAO and the RANZCO Teaching Award. firstname.lastname@example.org Dr. Vaibhav Sethi works at Arunodaya Deseret Eye Hospital as a vitreoretinal specialist. He graduated from Aravind Eye Hospital in Tamil Nadu and completed his fellowship in vitreoretina from the prestigious L.V.Prasad Eye Institute, Hyderabad. Dr. Sethi is a fellow of the International Council of Ophthalmology, London, U.K. He has to his accolade several hundred vitreoretinal surgeries including retinal detachment, macular surgeries, diabetic vitrectomies, scleral buckling procedures, and many others. Dr. Sethi has presented his work as an invited faculty at various national and international conferences, including the World Retina Congress, and has many awards to his credit. His areas of interest include macular surgeries, diabetic vitrectomies and complex retinal detachments. email@example.com Dr. Sherman Valero, MD, FPAO is an ophthalmologist specializing in diseases and surgery of the retina, vitreous and macula. He is currently a consultant at The Medical City, The Makati Medical Center and The American Eye Center in the Philippines. Dr. Valero obtained his medical degree from the UERM College of Medicine in 1993 and finished his residency training in Ophthalmology at the Makati Medical Center in 1998. He underwent subspecialty training both at the University of Hawaii, USA, and the University of Toronto, Canada, from 1999-2001. Dr. Valero is the past president of Philippine Academy of Ophthalmology and the Vitreoretina Society of the Philippines. firstname.lastname@example.org
| March/April 2021
The Vision Atlas
During the United Nations Friends of Vision Group meeting in February 2021, the International Agency for the Prevention of Blindness (IAPB) officially launched its Vision Atlas.* These are its key messages.
1.1 billion people have vision loss primarily due to lack of eye care services
live in low- and middleincome countries
are over 50-years-old
are women 18
| March/April 2021
this number will rise from 1.1 to 1.7 billion due to population growth and aging.
of vision loss is preventable.
Global economic productivity loss from unaddressed poor vision:
Leading causes of preventable vision los s include: Uncorrected refractive error:
Distance vision loss
Near vision loss
Age-related macular degeneration
Poor eye health leads to a increased risk of mortality.
Children with vision impairment are more likely to have poorer educational outcomes.
Other causes of vision loss
Eye health is simple and cost-effective and makes a real difference to people’s lives. As we build back health services post-COVID we need to make sure it is included,” Dominic Haslam, deputy CEO for Sightsavers.
* The Vision Atlas brings together data from the Vision Loss Expert Group, the WHO World Report on Vision, country-level monitoring data, and the The Lancet Global Health Commission on Global Eye Health. It has been sponsored by Allergan (an AbbVie company), Bayer, Seva Foundation, Sightsavers, CBM and The Fred Hollows Foundation. Hundreds attended the virtual meeting, which was organized by the UN Ambassadors from Antigua and Barbuda, Bangladesh and Ireland, with an address by H.E. Volkan Bozkir, president of the UN General Assembly. For more on this meeting, see the full story on www.piemagazine.org.
| March/April 2021
TREATMENTPIPELINE REGIMEN RESEARCH
Darn Near Magic
Curing Blindness with Implants and Chemically Induced Cells by Sam McCommon
This old cowboy’s on the lookout for the day there ain’t no more blindness.
uring blindness with technology has been the stuff of science fiction for decades — and even in science fiction it’s come a long way. Compare the early 1990’s depiction of Geordi La Forge on Star Trek: The Next Generation wearing a clunky visor to later iterations of the character with prosthetic implants, and you’ll see that even science fiction writers have to get more sophisticated with their imaginary technology. If you’re not a “Trekkie” or science fiction fan, fear not: That analogy won’t go any further. We’re much more in the Wild West era of “curing” blindness, though significant steps are indeed being made to bring science fiction to life.
Here, we’ll be focusing on two different treatments for retinitis pigmentosa (RP), both of which sound futuristic enough to make even the most grizzled and worldweary cowboy give them a long, hard squint and a grunt of approval. That both developments have both been published in Nature means they’re no joke: Observers would do well to keep their eyes on these projects for developments.
Artificial vision via implant Researchers based in Lausanne, Switzerland¹ have been developing a system that combines retinal implants with smart glasses that sport a camera and a miniature computer. This system would give blind people what’s essentially artificial vision. The team
| March/April 2021
is led by Diego Ghezzi, holder of the Medtronic chair in neuroengineering at the Laboratory of Neural Engineering at the Ecole Polytechnique Fédérale de Lausanne. For now, the system is still in its early stages, though the team has been working on it since 2015. But its implications are potentially huge, and it represents a major step toward letting the blind see. First, we need to establish a bit of background. Retinal implants for the blind currently exist, most notably the Argus® II (Second Sight, Sylmar, California, USA). However, current implants provide limited quality of life impact for patients for a few reasons. Indeed, a full third of those implanted
with Argus® II noted that it had a neutral effect on their quality of life after three years. Furthermore, most retinal implant patients stop using their implants within one to three years after their surgery. Now, as the researchers note, the currently existing technology is astounding and represents leaps over what was available previously. So what gives? A few things, really. First, these implants provide a limited field of vision — at best 20 degrees. As the Swiss research team’s paper published in Communications Materials, a subset of Nature, noted, 30 degrees of vision is the minimum to complete everyday tasks. They noted two significant problems with visual fields lower than 30 degrees. First, there’s not enough peripheral vision to allow for independent mobility — for example, crossing the street or navigating a crowd. This lack of independence could be what leads to the lukewarm quality of life improvements. If you still can’t move around on your own, life would be frustrating. Second, such a narrow field is mentally exhausting for patients because they have to continually scan an area while making a mental map of their surroundings. Imagine having to do that all day, every day. Sounds exhausting, indeed. Additionally, the current technology provides low image resolution, so that while the wearers can make out shapes and see light/dark patterns far better than, say, being entirely blind, they’re not exactly seeing in high definition either. Let’s give credit where credit’s due, though: It took a long time for computer or television screens to look any good, too. While the Swiss team’s device isn’t ready for tests, it’s showing significant promise in both mouse models and in virtual reality. Their prosthesis, dubbed POLYRETINA, embeds nearly 10,500 functionally independent photovoltaic pixels. The smart glasses would send signals to the photovoltaic pixels which would stimulate the retina to produce “dots” of light, without color for now. The theoretical visual acuity reported by the team would be 20/480, with a much broader field of vision than competitors.
It’s important to note that this concept has not yet been tested on humans, nor does the team claim it’s ready to be. But if this doesn’t whet your intellectual whistle, well … you’re a tough nut to crack, friend.
Chemically induced photoreceptor-like cells: Presto, change-o On March 10, 2021, the FDA granted Orphan Drug Designation to chemically induced photoreceptor-like cells (CiPCs) for the treatment of RP. The designation was granted to CiRC Biosciences (Chicago, Illinois, USA), which can now use the designation and the government funding that will likely follow to make significant strides in combating RP. In an April 15, 2020 publication in Nature², the team behind the treatment noted that a set of five small molecules can transform fibroblasts into rod photoreceptor-like cells. When they transplanted these photoreceptor-like cells into the subretinal space of mice, it led to “a partial restoration of the pupil reflex and visual function.” Apparently, CiPCs and their in vivo rod cell receptors have very similar gene expressions. The chemical conversion process takes less than two weeks, though the team noted that optimization of the team’s process may lead to greater conversion efficiency. As it is, the low conversion efficiency is one of the current main impediments to utilization of the technique.
Notably, in the study, 6 of 14 mice demonstrated improved pupil reflex function. That’s just less than half — but the team pointed out that a lack of cell survival during transplant may have been responsible for the lack of improvement in some mice. This biotechnology is in its nascent stages, and with additional research and funding we can expect to at least see more of the same — if not outright breakthroughs. That a cocktail of chemicals can take fibroblasts and transform them is nothing short of extraordinary. The possible future implications here are also enormous. If some chemicals plus a type of cell equals another type of cell, well … might that not work in other ways as well? Have we discovered a modern form of alchemy that actually works? Yes, the “we” above is overly generous to this publication since “we” certainly didn’t figure CiPCs out. But it’s human nature to celebrate the achievements made by our species, just like sports fans celebrate when “their” team wins. And hey, if anything’s a cause for celebration, it’s curing blindness.
References: Chenais NAL, Airaghi Leccardi MJI, Ghezzi D. Photovoltaic retinal prosthesis restores highresolution responses to single-pixel stimulation in blind retinas. Commun Mater. 2021; 2: 28
Mahato B, Kaya KD, Fan Y, et al. Pharmacologic fibroblast reprogramming into photoreceptors restores vision. Nature. 2020; 581: 83–88.
Changing one cell into another really is like a magic trick.
| March/April 2021
APTOS-APOIS Updates At-Home Monitoring and Patient-Centered AI by Sam McCommon
ret in o
t h y, g l a
We don’t have a uc crystal ball, but om a an we feel comfortable dv i guessing that the advances currently taking place are here to stay. Though their development seems inevitable, it may well have taken much longer sans pandemic to kick that development into high gear. There’s that old cliché about he wa necessity being the mother of y of the futu re. invention — and so far, no one has seen fit to disprove it. su
al acu it
st ing are
That’s a good thing, really, but it’s not entirely understood yet. To help understand it, the Asia-Pacific Teleophthalmology Society (APTOS) regularly holds webinars to discuss advances in telemedicine, featuring true leaders in the field. Their most recent webinar (an APTOS-APOIS
The COVID-19 crisis we’ve been going through for the last year, as of this writing, is fortunately nowhere near the magnitude as those mentioned above. But it’s profoundly accelerated extant trends — and there have been few buzzwords more popular in the medical world than telemedicine.
But history has shown that crises inevitably birth societal advances, often technologically. The long-running crisis of the Comanche Wars in Texas popularized Samuel Colt’s revolver, and led to the much-romanticized vision of the gunslinging Wild West. The First World War drastically accelerated the development of avionics, automobiles and factory efficiency; the Second World War resulted in jet engines, rockets, space programs and nuclear physics. That these advances stemmed from mass human suffering is perhaps one of the greatest paradoxes of our species.
joint event) centered around advances di ab et in at-home monitoring and artificial intelligence (AI) solutions. At-
obody looks forward to a crisis. The turmoil, instability and anxiety experienced while living through one makes them, well, let’s just say “un-fun.”
At-home monitoring solutions: Tech tools to test Professor Gavin Tan is a senior consultant at the Retina Center at Singapore National Eye Centre (SNEC) and plays a crucial role in the SNEC Ocular Reading Center as well, which provides image grading for Singapore’s national diabetic screening program. As Dr. Tan pointed out, telemedicine isn’t a new concept at all — we’re just getting better at it. It’s not even a
| March/April 2021
disruptive process, either, as it follows essentially the same pattern physicians are used to: collect patient data, interpret the data, and then provide care for the patient. Newer, better imaging tools developed over the last couple of decades make certain home screening processes truly viable for the first time, and allow much greater efficiency in clinics. It’s currently best suited for diabetic retinopathy. Remote imaging sent to an asynchronous grader to later be assessed by an ophthalmologist saves time, reduces office crowding, and
can even prevent unnecessary visits altogether. Remote imaging isn’t the best way forward in all cases, of course. Dr. Tan pointed out that he finds it to be most useful in more stable patients, as well as in those who don’t require injections. At least for now, anti-VEGF patients, for example, still have to be within arm’s reach. When comparing athome ultrawide field OCT imaging with traditional slit lamp examinations, Dr. Tan noticed very little difference. At-home imaging techniques were also used for glaucoma, which were then sent to ophthalmologists — after which medications were mailed directly to the patient. No visits needed. One major upside Dr. Tan noted is that patient satisfaction with this program was upward of 90%. Furthermore, physicians who might traditionally see 20 patients in an afternoon could “see” nearly three times that many by examining remote images. Dr. Tan is also piloting a new at-home visual acuity (VA) self-check app for patients to use. The app encourages a patient to get the image as stable as possible, but even then there can be mistakes. Odds are these kinks will be worked out in the near future.
Digital Diagnostics. Digital Diagnostics was the first company in any field of medicine to get FDA approval for autonomous AI diagnostic tools. Just for reference, Dr. Abramoff holds 17 patents and has 31,000 medical citations under his belt. So, when he speaks, we listen. Autonomous AI diagnostics for diabetic retinopathy (DR) are here already — they’re not science fiction. They were approved by the FDA in 2018 and, since then in the United States, check-up points can be found in grocery stores and other diabetic point-of-care locations. Just recently, Medicare has begun to cover these checkups at a rate of around $55. That’s a huge step forward. Autonomous AI means there’s no human oversight, which means lightning-quick diagnoses as well as easy integration with electronic medical records and automated billing. But it also means that legal liability falls on the creator of the AI. As opposed to assistive AI, which is merely a tool assisting a clinician, autonomous AI requires no human oversight. Making algorithms that can detect DR are fairly straightforward, noted Dr. Abramoff. What’s difficult is implementing them. For example, it took
One neat upshot from these athome checking apps is when they’re more fully developed, they’ll be able to seamlessly integrate with electronic medical records. Eventually, patients may be able to do a thorough at-home VA test. We’re not quite there yet, but with the blistering pace technology moves, it may be soon.
eight years for their AI to clear FDA approval. In addition to that, there are lots of other questions to answer — to the point where you’re almost entering sci-fi visionary Isaac Asimov’s territory. For one thing, Dr. Abramoff wanted to prevent a potential backlash against AI, so had to deeply consider the ethics behind its use — in terms of data, bias, patient understanding and more. He specifically cited “inappropriate” gene therapy in the early 2000’s which cost lives and set the field back decades — as well as the multibillion dollar scandal of Theranos — as events that make people wary of tech in medicine. He’s got a point. So, rather than disrupting the industry with AI like, say, Uber did to taxis, his company decided to work within the existing medical framework and focus strongly on ethics. For now, he cites three main ethical focuses for his AI: Do no harm, maintain patient autonomy and maintain justice. That’s a good start, and we’re very glad someone with a solid ethical founding is leading the charge in medical AI. Nobody wants Skynet in their future.
Editor’s Note: The joint Asia-Pacific Teleophthalmology Society-AsiaPacific Ocular Imaging Society (APTOS-APOIS) webinar was streamed live on February 19. Reporting for this story took place during the event.
Patient-centered AI The second speaker is a true heavyhitter: Dr. Michael D. Abramoff from the University of Iowa and founder of Would a robot gunslinger have ethics in its programming?
| March/April 2021
The Race for Success in Home Monitoring Only Those with the Broadest Vision will Prevail by Luis Diaz-Santana
’ve focused my professional life on ophthalmology for more than 20 years, and you know what? I can’t recall a more stimulating time to be pushing the boundaries in this challenging and fast-paced area of medicine. Ophthalmology is brimming with innovation in all its subspecialities — just as the world begins to rebuild from the pandemic with renewed purpose and urgency. I sense the mood every day in my role as head of ophthalmology at Cambridge Consultants. We’re having plenty of discreet conversations with bold, ambitious start-ups and multinationals alike intent on bringing transformational product ideas to market sooner, rather than later. With a lengthy record of working with clients to help enable breakthrough innovation, it appears our advice is at a premium right now. I can live with that! The trend was set before the sudden emergence of the novel coronavirus, of course. The relentless pressure on the global healthcare system from our increasingly aging population was already driving rapid advances in medical technologies. And the stakes are higher: Now, we are dealing with a worldwide health emergency. A significant consequence of this has of course been the swing toward longdistance patient and clinician contact. The telemedicine race — worth many billions of dollars — is well and truly on. The implications for innovation in ophthalmology are clear. Preserving eyesight remains the key driver for innovation, but growing in importance
is the need to improve the patient’s experience throughout their entire treatment and — increasingly these days — the virtual experience component of this journey. Elevating the journey is valuable for product differentiation and crucial to market adoption. New treatment options must respond to two main objectives. One, reduce the number of touchpoints between the patient and healthcare provider and two, increase the patient’s independence by allowing them to selfmanage their treatment. These very welcome and powerful benefits necessitate the need to monitor the patient remotely, so that the healthcare provider is alerted to the need for intervention when necessary. This brings me to the central question of my article: What is the key to unlocking successful home monitoring in ophthalmology? I have a succinct answer to this multileveled and complex problem: Seek the broadest possible viewpoint and tap into a comprehensive blend of competencies. As the graphic here shows, the new kind of home monitoring device relies on a system design that encompasses a great swathe of influences. The patient group and the visual need in question are just the beginning.
| March/April 2021
Devices to be used at home need to deeply understand the behaviors and journeys of the patient and their support network. They must consider important usability factors, from age to mobility, serviceability and much more. To glue everything together, of course, it is vital to have a firm grasp of the science and technology that will ensure the operation of any device is reliable, predictable and safe — as well as transformative for clinicians and patients. For home monitoring, that should include an understanding of the role of off-the-shelf devices such as smartphones. It is possible to use their functionality to monitor a number of body parameters, such as heart rate, activity, gait, eye movements and breathing patterns, to mention just a few. Often, this is possible with out-of-the-box sensors in the device, but sometimes an ergonomic holder is needed. In other instances, the smartphone might just be used to
and frequency of data collection would need to be carefully considered. Certain parameters may need to be monitored very frequently, making a strong argument for smart implant devices that can monitor eye health continuously. Intraocular pressure (IOP) is a case in point, as it varies significantly across the day. In glaucoma patients, an implant to monitor IOP day and night will significantly improve their care and outcomes. But once again, specific product specifications will be dictated by a host of factors, all of which need to be understood before development begins.
process, log or transmit information. Smartphones and tablets lend themselves to visual tests such as the classic Snellen eye chart, color vision tests, the Amsler grid test and so on. The team here at Cambridge Consultants has plenty of experience in this area, including the development of an innovative perimetry testing concept capable of offering simple, affordable and fast glaucoma screening. It’s a smart approach, by the way, to consider gamifying a test — which is a great way to improve patient engagement and adherence. I’ve taken part in many “smartphone versus standalone” debates when it comes to home monitoring innovation. Take an application such as fundus photography, for example. It can be achieved with the camera of a smartphone along with a simple lens/ flash adaptor. This approach has a lower development cost and quickens time to market. But on the downside, it is difficult to use unassisted, gives a very small field of view (up to 10°) and does not give access to the raw data that’s needed for better analytics.
Depending on the quality of the data required, it may be better to use a standalone device that is able to produce high quality data consistently. What might appear a slower, more expensive route would actually be more robust and easier to control in future generations. In both cases, the device must be easy to use and minimize the risk of user errors to ensure high quality data consistently. My advice would always be to consider market and user needs, and don’t leave out any of the other stakeholders involved in that patient’s journey so that the most appropriate medical device can be deployed accordingly. Optical coherence tomography (OCT) imaging is an example where a smartphone is not suited to collecting data. Here, a home monitoring system would require the specialized technology of an independent, standalone device to collect and process the data. Technical, ergonomic and safety considerations dictate the form factor of the device. For example, head-worn versus tabletop devices are both possible options, but factors such as age group, dexterity, lifestyle
As I said at the start, an exciting race for success is definitely on — but I’d urge entrants to pause long enough to view their potential opportunities from the broadest possible perspective.
Editor’s Note: Dr. Luis Diaz-Santana is the head of ophthalmology for Cambridge Consultants, United Kingdom. luis.diaz-santana@ cambridgeconsultants.com
| March/April 2021
WOMEN IN OPHTHALMOLOGY
The Eclectic Approach to Becoming a CEO
t r a p
by Nikki Hafezi, MAS IP ETHZ
In Part 1 of this two-part Women in Ophthalmology story, Nikki Hafezi shares how her journey in ophthalmology began. a living, and I was able to meet and engage with the medical and scientific staff members. I earned enough to comfortably sustain my life as a single woman in Los Angeles, and I got to work with a wonderful team.
Introduction to medical fundraising
graduated from UCLA with a Bachelor of Arts in English and a minor in Spanish with the aspirations of pursuing a master’s degree in either law or education. However, financial constraints meant that before I could do that, I had to find a way to support myself and save enough money to go back to school.
One of the charity’s board members was also the
I took a paid position to develop and implement a nature-focused educational program for urban school children in Los Angeles. I started this job in 2001, and well, 9/11 happened not long after I had started. The charity’s annual income dropped significantly, as most of our donors were now directing their donations to 9/11 relief efforts in New York. My employer transitioned me from the department of education to fundraising to sustain the program. And this is where I found a hidden talent: storytelling. I discovered that the secret to successful fundraising is being able to tell a story that resonates on a personal level with the target audience. As Americans say, “you need to tug at the heartstrings to make the music play.”
president of a large private hospital in Los Angeles. He took notice of what I could do, and he asked me to join his team at the hospital. This transition was my first step into medicine and medical research. I learned about medical fundraising,
in the context of grateful patients; raising money for capital funds; and directed research projects with industrial partners and clinical trials. I loved my position because the fundraising team was filled with spirited individuals who truly enjoyed what they did for
| March/April 2021
Although I really loved my position at the hospital, I knew that in order to climb the career ladder, I needed managerial experience, so I transitioned to a management role in development for a public policy organization. In this position, I led a small team that was focused on raising funds and building alliances with the private and public sectors. I engaged with governmental organizations to develop private-public partnership relationships to help support the programs that the organization provided. In other words, I coupled my experience in traditional and medical fundraising with the network relating to public policy and governance. Understanding how people make decisions has always been fascinating to me, so it probably does not come as a surprise that I developed an instant fascination for politics. What I found is that fundraising and politics almost always go hand-in-hand, and telling a compelling story can influence people’s decisions about both.
Working within the academic sector The public policy space was very interesting as well as challenging, but I did not lose focus on my educational
goal of pursuing higher education. At this point in my career, I had saved a little bit of money, but I thought I would try to combine my future education with an executive program. I wanted to continue to work and enroll in a master’s program. I thought that the best option would be to seek a position at a university, which might have provided a discount on the tuition and allow me to continue to work. My dream was to work for my alma mater, UCLA, but unfortunately, they were not hiring at the time. So, I applied to UCLA’s crosstown rival, USC (University of Southern California). I have to admit that despite my experience in fundraising, the open position had a job description that I did not quite understand. It was for an “Industrial Liaison Officer’’ with mention of “being able to handle intellectual property, being able to bridge the gap between researchers and industry, and helping facilitate relationships with invested parties.” I was always up for a challenge, so I thought I could at least learn more about the position by applying. The first part of the interview was with Dr. Howard Phillips, an engineer, and a very close colleague of Prof. Mark Humayun at USC. Dr. Phillips told me that he was looking for a candidate who had drive and spirit, and that the other aspects of the position can be learned. He liked me as a candidate probably because of my fighting spirit, and then he recommended that I meet Prof. Humayun. This part of the interview process took no more than three minutes because he said, “If Howard recommends you, I trust Howard.” What I learned quickly thereafter was that to be great, you must surround yourself with good people who you trust. It is exactly what Prof. Humayun did. Due to his rockstar status, I never really saw Prof. Humayun because he was either traveling, in meetings, or in surgeries. However, he managed to do the impossible, because he had really, really good people. Another person was Prof. Gerald (“Jerry”) Chader, the former IOVS chair and one of the board
members and past presidents of the Foundation for Fighting Blindness. Jerry showed me the ropes and was my lifeline to understand the ins and outs of the research lab because everything was new to me.
Speaking the industry’s lingo But in any case, I had a plan for this position and a personal timeline. I wanted to streamline my responsibilities, goals and milestones, and be able to automate them in a way where I could pursue my education and maintain this position. I knew that my position needed me to secure money from our industrial partners. That was key. I already knew which partners I needed to go after: I just needed to understand what motivated them. I needed to know what story I needed to tell them for them to support us. To do this, I needed to be in the laboratories, talking to the researchers, understanding the technology, understanding the problems related to the technology, and so on. Basic researchers and industry people talk to each other, but they often speak different languages. They usually have the same goal: to create a superior technology, but it’s difficult to get them to understand one another during the developmental process. Industry’s concern is the bottom line, and to make it to the market before the competitors, while the researchers don’t want to feel pressured to do suboptimal work just because of financial demands. A balance has to be kept. I acted as a liaison between them to get everyone on the same track, find common ground, keep everyone motivated, and push the process forward. It wasn’t easy, but my role and function were essential to the life of the projects because if the industry partners kept finding value in collaborations, the research funding remained.
Going back to school... In 2006, I thought it was now time to
go back to school because my work became second nature. All the industrial partners knew and could count on me. My position at USC was secure for about six more years assuming that I continued to do good work. While I was deciding on which master’s program to pursue, Prof. Humayun asked me to prepare for and attend ARVO (for the first time) to meet with our industrial partners. Traveling was an exciting aspect of the position, which I hoped that I would be able to do. I enthusiastically jumped at the opportunity. Little did I know how impactful ARVO 2006 would be. I met my (future) husband, Farhad. It was like a whirlwind because I had to decide whether to stay in Los Angeles or leave the country so Farhad could continue with his career track as an aspiring professor in ophthalmology. Since I was younger (and I thought my skill sets and education had an easier time transferring to Europe than he would have moving to the U.S.), I agreed to move to Zurich. When I told Prof. Humayun I was leaving, he told me that one of the companies that I was involved in was going to be a successful spin-off company, and he would like me to lead the charge. At the young age of 26 years, I declined the offer because I ultimately had to choose love over my career. This company was later sold, but I think it is important to never look back on lost opportunities.
...and ending up in Switzerland! After the dust settled from my whirlwind decision to move to Europe, I wanted to find a job. I naïvely thought that fundraising was a global profession, and all research
| March/April 2021
WOMEN IN OPHTHALMOLOGY
Geneva University Hospital. So, I had to decide again if I were to follow him to Geneva or stay in Zurich and keep growing my company. At this time, I was pregnant with our second child, and I knew that becoming chair was a once-in-alifetime opportunity for him. So, I agreed to downscale the company to move to Geneva to support him.
Biomimentic Microelectronic Systems Engineering Research Center (BMES ERC) Team from USC (2006).
groups need to continually raise money to sustain. So, after ringing a few doorbells of academic institutions, I realized that the concept of funding diversification outside of traditional grant writing was non-existent. In fact, the concept of direct research projects and working with industry wasn’t really a thing here: it was (almost) viewed as biased research. So, as a pragmatic person, I relied on another skill that I needed to fine-tune if I was ever going to make it in Switzerland. This skill was in relation to intellectual property, with a particular focus on patents.
Of intellectual properties (IPs) and patents Spin-off companies in the MedTech sector are typically based on patent(s). And, I saw firsthand at USC the power and influence that a patent can have in the industry. While I knew that I did not want to become a patent attorney, I did know that I needed to be well versed with the European Patent Office if I wanted to offer these services to future clients or be hired for a company. The Swiss Federal Institute of Technology (ETH) in Zurich had a master’s program dedicated to intellectual property, and it was a full intensive year program. Although my initial application caused some questions because I was not the typical applicant, after perseverance, I was accepted. The course was a challenge for me because the lectures were in a mixture
of German and English. My language skills in German were limited at the time, but I managed with extensive after-hours of studying to keep up with my bilingual classmates. I was also pregnant with my first child during the course, which made concentration and late-night hours difficult.
While I held onto the key clients, I reduced the employees to just me. This allowed me to support Farhad in his new position as well as manage a new life with two babies and learn a completely new language.
The birth of Light for Sight Foundation
During this intensive year, I was also During this period, Farhad and I asked to develop and write a large founded the basis of the Light for European Commission grant for nine Sight Foundation. academic institutions in Europe. The focus of the grant was to reduce In 2014, our family decided to move national fragmentation among retinal back to Zurich for personal reasons. research academic groups. We decided that we would start a The final grant was over spinoff company based 100 pages. Little did I on the research that know at the time that this was conducted in grant program, called Farhad’s laboratory the “FP-7 Program” at the University was one of the most of Geneva, which This story will be competitive research produced two continued. For more on programs in Europe. I patents. We Nikki Hafezi’s story, stay learned in 2007 that acquired both tuned for Part 2 in PIE the grant was funded. patents privately and Issue 18. founded a company, which is known today as Holding a double EMAGine…
diploma (master’s degree + motherhood)!
So, after graduating with my master’s degree, I was able to kick-start my own consulting company called GroupAdvance Consulting. My first client was the management of some of the projects included in the grant. This consulting firm grew to about five people and continued to sign new clients until 2010. Farhad became the new chair of ophthalmology at the University of Geneva and eye clinic director at the
Contributor Nikki Hafezi is partner of GroupAdvance (Management) Consulting GmbH, Zug, Switzerland; chief executive officer and board member of EMAGine AG, Zug, Switzerland; head of Strategy, Business Development and Licensing, The ELZA Institute, Zurich, Switzerland; and co-founder and managing partner of the Light for Sight Foundation, Zurich, Switzerland. email@example.com
| March/April 2021
Unique , Smart and A.I. solutions for Eye Care Specialists!
FAST Get all the measurements in 3”
FRIENDLY Easy-to-use and patients friendly
HE Vision Group (article or ad)
ACCURATE Suitable for adults and kids
PORTABLE Take it everywhere
MULTIFUNCTIONAL Widest range of Application
SAFE Safety Working distance > 1 m
www.adaptica.com firstname.lastname@example.org Adaptica srl: Via San Marco 9/H, 35129 Padova (PD), Italy
MADE IN ITALY
| March/April 2021
COVID-19 SPECIAL REPORT
Ophthalmic Business Performance Strong and Stable despite COVID-19 by Andrew Sweeney
n case it escaped your notice, the last 12 months have been a little unusual. When the pandemic bagan to impact the West in March 2020, frontline ophthalmology clinics were hit hard. Smaller practices were particularly affected. Attention to budgets and finances became more important as many economies slowed, and to this day, ophthalmic practices face difficulties that would have been unimaginable in 2019. Thus, Financing in the Time of COVID, a
webinar organized by Eyecelerator, was the ideal online event to take stock of ophthalmology’s performance over the last 12 months and consider its future progression. Through a partnership between the American Academy of Ophthalmology (AAO) and the American Society of Cataract and Refractive Surgeons (ASCRS), Eyecelerator is a platform to connect “entrepreneurs, investors, companies and ophthalmologists to advance ophthalmic innovation through conferences, live streams and networking.”
| March/April 2021
Defensive growth and convertible bonds
Dr. Gil Kliman, a digital health investor with Interwest Partners (Menlo Park, California, USA),, acted as moderator. He began sharing that ophthalmology’s performance over the past 12 months has been better than expected and has outpaced expectations at the outset of the pandemic. According to Dr. Kliman, Eyecelerator had plans for two live events with up to 1,200 attendees in 2020 but in response to COVID-19, the events were moved online. He used this as an example of how the pandemic silver linings — in this case, allowing his organization to more than 5,000
viewers via online programming. This focus on the “positives” is reflected in ophthalmology’s overall financial performance. “Equity markets are up by over 20 percent. Ophthalmology is doing very well and this development is being driven by factors including defensive growth, interest rates and a strong appetite to put capital to work,” said Andrew Gitkin, managing director and co-head of Health Care Investment Banking at Raymond James (St. Petersburg, Florida, USA). He described how these changes are leading to increased development in bio-pharma research and development, acting as another catalyst to propel ophthalmology’s growth and insulating it from the worst effects of COVID-19. This strong performance is exemplified by Glaukos (San Clemente, California, USA), a medical technology and pharmaceutical company focused on ophthalmology. According to the company’s CFO and Vice President of Corporate Strategy and Development Joseph Gilliam, Glaukos responded to constricted cash flow at the outset of the crisis by considering new financing models including government programs, convertible bonds and receiving credit facilities. According to Mr. Gilliam, Glaukos analyzed its options based on five key metrics: cost of capital, net proceeds, flexibility/risk, investor relations and execution risk. The company initially considered using a revolving credit facility or structured debt, before opting for a convertible bond offer worth $250 million. This increased Glaukos’s cash and other equivalents to $416 million by December 31, 2020, providing what Mr. Gilliam described as “a very bullish signal to our investors” and a good example of how businesses could explore new options for capital.
understand how we progress into the clinic, we can have confidence in moving forward with ophthalmology,” said Wende Hutton, general partner at the venture capital firm Canaan Partners (Menlo Park, California, USA). Ms. Hutton’s comment came during the second part of the webinar that focused on private financing and exemplified the buoyant attitude which characterized the participants’ views on ophthalmology’s financial health. According to William J. Link, PhD, the managing partner of Flying L Partners in Steamboat Springs, Colorado, USA, both public and private financing in ophthalmology is healthier than could have been expected one year ago. He characterized the market as “stable and solid,” and a good environment for investment going into 2022. What is certain is that despite COVID-19, major innovation continues in ophthalmology. The webinar’s participants (audience and panel alike) were asked about which innovation sector would see the most interest from investors and strategics in 2021, with options ranging from dry eye to glaucoma. The clear winners were presbyopia, followed very closely by retina, which will come as no surprise to our readership.
Other topics raised as good investment targets included myopia, thanks to its pervasiveness in East Asia. Dr. Nick Pliam, MD, PhD, a partner at Chinafocused investment firm Decheng Capital in Menlo Park, California, said that in meetings with his Chinese colleagues, he is often the only person present without eyeglasses. Technology associated with COVID-19, like telemedicine, was also noted as a good investment opportunity. Vaccination programs are ongoing in many parts of the world and we can optimistically say that the worst of the crisis appears to be over. Ophthalmology is in better health than was predicted; the state of the industry was perhaps best exemplified by the Worldwide President of Surgical Vision at Johnson & Johnson Vision (Jacksonville, Florida, USA) Warren Foust. “Business responded quickly to the pandemic than we expected. Speaking for Johnson & Johnson Vision, there are good underlying fundamentals to the industry and we have a high level of confidence. It is business as usual going forward,” he concluded.
Editor’s Note: Eyecelerator’s Financing in the Time of COVID webinar was streamed live on March 3, 2021. Reporting for this story took place during the event.
Ophthalmology is strong and stable “We are probably in our best public relations heyday in five to 10 years, so we haven’t seen the impact on investment that we would have expected in Q2 last year. As long as we can
Despite expectations, ophthalmic business remains strong.
| March/April 2021
Webinar Reminds Ophthalmology about Retina Awesomeness by Andrew Sweeney
here are moments in history when countries, people, cultures and the like experience a collective moment of inspiration. This is when remarkable developments in science and art can be achieved — for example, one such moment in European history was the Renaissance, a period of rebirth and rediscovery in art, science and culture. Is ophthalmology experiencing a similar “zeitgeisty” moment in regard to retina? Perhaps so. And while all of ophthalmology excites the Media MICE team, we have witnessed some
fascinating developments in retina as of late. This is fitting as the retina is a great symbol of ophthalmology — it is the means by which we create two dimensional images of the visual world and it acts as an image sensor for the brain. A simple explanation of retina function from a lay website like Wikipedia which says “light striking the retina initiates a cascade of chemical and electrical events” has a real effect of profundity.
| March/April 2021
Retina: It’s totally far out Dude
The retina is indeed awesome — not just in the California ‘90s, skater boy sense — but it is truly something that inspires awe in those who see and study it. Thus, the name “Retinawesome” is far more prescient as a title for an ophthalmology webinar than one may initially suspect. The 8th meeting of this online symposium, which took place on February 20, was another development in retina’s apparent “Renaissanceesque” moment. At nearly 5 hours long, there was certainly plenty of material for the webinar’s viewers to digest. It drew ophthalmologists from over a dozen countries in four continents, all presenting their own retina-related case studies. Issues ranged from diabetic vitrectomy, to managing severely
traumatized eyes and retinal surgery techniques. A reasonable place to start with the Retinawesome 08 webinar is A Very Reasonable Approach for Treating the Refractory Macular Hole. This presentation was given by Dr. Yusuke Oshima from the Oshima Eye Clinic in Osaka, Japan. Dr. Oshima’s report focused on a new surgical technique involving the application of sub-retinal fluid to close refractory full thickness macular holes. Dr. Oshima described one surgical case study that involved a patient with macular hole retinal detachment caused by vitreoretinal traction and a history of proliferative diabetic retinopathy. He used what he described as standard (non-inverted) surgical techniques in an attempt to close the patient’s macular hole. However, he was unable to do so. He responded by using the subretinal fluid technique successfully; this resulted in no retinal penetration and a postoperative visual acuity improvement from 20/200 to 20/100. Of course, macular holes are traumatic for all patients, but there are different forms of macular hole trauma. For a deep dive into the vagaries of macular holes, watch Chronic Traumatic Macular Hole by Dr. Wai-Ching Lam from the University of Hong Kong. Dr. Lam reported that trauma is the second most common cause of macular hole. Dr. Lam also stated that macular hole incidence is 1.4%. This is followed closely by globe trauma, which occurs at a rate of 0.15%, and open globe injuries, which are frequently caused by antero-posterior vitreoretinal and tangential retinal traction. While spontaneous closure occurs in 50% of pediatric patients, this drops to 28.6% among adults, and to zero after 67.3 weeks. Dr. Lam recommended the use of surgical techniques including pars plana vitrectomy and epiretinal membrane peeling, which has a 73% success rate in treating macular holes.
Peeling and zipping The keynote speaker of Retinawesome 08 was Dr. Barbara Parolini, an Italian ophthalmologist who operates
Zipper syndrome… different and much less fun than ziplining.
her own clinic in San Martino Buon Albergo, Veneto. She presented Intraoperative OCT: The Beauty of Confirmation, an examination of optical coherence tomography (OCT) and the guidance it offers when peeling membranes. Dr. Parolini stated that peeling requires OCT guidance as both the retina and membranes are transparent (as opposed to the choroid which is colored) and thus require a distinguishing method. Dr. Parolini reported that staining is offered as a solution, but in her words “it does not solve all the problems.” As examples, she cited an inability to see contrast, difficulty in verifying the position of an internal limiting membrane (ILM) flap under air, and in verifying the reaction of the retina during peeling at the risk of iatrogenic lesions. Emphasizing the efficacy of OCT, she said it is particularly useful when there is no contrast for the presence of choroidal atrophy, when light reflexes work under air tamponade, and finally, when the surgeon has concerns about inducing iatrogenic lesions.
mention Dr. Athanasius Nikolopoulos, who presented Zipper Syndrome Treatment in Retina Detachment. Zipper syndrome was described as “multiple tears in one meridian in a retina detachment without proliferative vitreoretinopathy.” Dr. Nikolopoulos recommended that if a clinician discovers zipper syndrome, then they should not rely on a simple primary vitrectomy, and should instead use a 360 laser.
Editor’s Note: The 8th Retinawesome webinar was streamed on February 20, 2021 and was organized by the Retinawesome group headed by Dr. Hudson Nakamura, a retina and vitreous specialist based in Goiânia, Brazil. Held roughly once a month, the webinars are available to view on the YouTube Channel: Retinawesome Retina & Vitreous International.
We would also be remiss if we failed to
| March/April 2021
OIS 2021 COVERAGE
Real World Results Highlight Gene Therapy Success by Andrew Sweeney
f you could go into your DNA to take a look at your genes in detail, and add or replace them to your heart’s content, what would you do? Personally, I wonder if I would be able to cure my allergies to peanuts and almonds, which has always been something of a drag while traveling. Maybe you could have some fun with your eyes, perhaps giving yourself heterochromia … or X-Men-style super powerful laser beam eyes that could shoot objects in space. Okay, maybe the last point would be a diabolical step too far, and these examples may be dubious, but there are some pretty interesting ophthalmological developments in this field. New treatments are emerging for a wide array of conditions, from age-related macular degeneration (AMD) to X-linked retinitis pigmentosa. Indeed, it is an exciting time to be involved in gene therapy. The recent Ophthalmology Innovation Summit (OIS) Gene Therapy Showcase served to highlight gene therapy’s remarkable development, including
presentations from companies in the field. Covered below is the second part of the webinar — the Gene Therapy Panel Outlook — which was an informative conversation about gene therapy from some of the field’s leading thinkers.
Gene therapy: It’s alive! Moderator Dr. Thomas Ciulla, clinical professor of ophthalmology at Indiana University School of Medicine (USA), opened the panel by describing gene therapy in retina as “the epicenter of so much innovation.” Indeed, ophthalmology has the distinction of getting the first FDA approval for gene therapy with voretigene neparvovec-rzyl (Luxturna; Spark Therapeutics, Pennsylvania, USA). Administered as a subretinal injection, Luxturna was approved for patients with confirmed biallelic RPE65 mediated inherited retinal disease. “We are now seeing gene therapy
| March/April 2021
working, it’s a real thing, it’s not a myth anymore. We are seeing patients going one or two years without receiving injections; it’s exciting to be part of this evolution in gene therapy,” said Dr. Arshad Khanani, a clinical associate professor at the University of Nevada (USA). Dr. Khanani described his work with suprachoroidal delivery, a new potential route for drug administration to the posterior segment of the eye. This involves the delivery of an injection into the suprachoroidal space, or a subretinal delivery via the Orbit Biomedical’s 510k approved microcannula, which has now been acquired by Gyroscope Therapeutics (London, UK). Along with Dr. Jeffrey S. Heier, the director of retina research at Ophthalmic Consultants of Boston (USA), Dr. Khanani was heavily involved in clinical trials examining suprachoroidal delivery. “The real world data on diseases like neovascular AMD and diabetic macular edema has shown that undertreatment
of patients almost universally prevents us from achieving the outcomes seen in gene therapy phase 3 studies. These results show us the means of achieving long-term durability and maintenance, and doing away with compliance as an issue,” Dr. Heier said.
Inflammation, such a hot topic right now Dr. Jose-Alain Sahel, chairman and director of the Department of Ophthalmology at the University of Pittsburgh School of Medicine (USA), talked about his work with optogenetics. Dr. Sahel is working on optogenetic vision restoration, a technique in which “cells in the retina are genetically modified to express light sensitive proteins.” According to Dr. Sahel, this represents a gene independent approach and while it cannot cure disease, optogenetic techniques are showing considerable efficacy in mitigating damage.
The exciting developments taking place in gene therapy-focused ophthalmology would be impossible without high-level manufacturing support. For Dr. Peter Francis, PhD, chief scientific officer and therapeutic area head of ophthalmology/ retina at 4D Molecular Therapeutics (California, USA), the complexity of gene therapy had given rise to unusual phenomena like empty capsids during the manufacturing process. Many were produced whole but were unpackaged with the trans-gene, meaning a lot of potentially inflammation causing protein could be delivered. Dr. Francis said that with modern manufacturing techniques a very high ratio of the capsids now contain the therapeutic trans-gene which helps to reduce inflammatory responses. Inflammation is an important issue in ocular gene therapy, and was a topic of considerable note during the panel. Dr. Glenn Yiu, PhD, an associate professor at the Department of Ophthalmology at the University of California, Davis
(USA), spoke about the various forms of inflammation. “There is a lot of discrepancy in the literature, but if you see inflammation very rapidly within a week, it is unlikely to be a trans-gene expression and is more likely to be a result of the viral particle. If you see inflammation at the one month mark, it is more likely to be the transgene, but it’s a very murky field and studies are ongoing,” Dr. Yiu said.
Editor’s Note: The Ophthalmology Innovation Summit Gene Therapy Innovation Showcase webinar was held on February 18, 2021. Reporting for this story took place during the event. On March 4, 2021, part 1 of this coverage was published on piemagazine.org.
Phase 1 Clinical Trial Studying Remote Monitoring with Home OCT in DME and AMD Patients Begins
e all know that regular monitoring is crucial to preserve sight in patients suffering from progressive diseases like wet age-related macular degeneration (nAMD) and diabetic macular edema (DME). We also know that reducing the frequency of office visits — especially during a global pandemic — is necessary to ensure continued disease management. This is where home monitoring could be a real sight saver, especially since the majority of nAMD and DME suffers are elderly or have preexisting conditions. Therefore, to learn more about the feasibility and efficacy of home monitoring, Notal Vision, Inc., will provide Home OCT services (through its Notal Vision Diagnostic Clinic) to AsclepiX Therapeutics and its AXT107 phase 1 clinical trial program.
In this trial, subjects with DME and nAMD (who also participate in the AsclepiXsponsored CONGO and SHASTA studies) will perform sequential daily self-imaging of their eyes with the self-operated Notal Home OCT device at home. This data will be transmitted from the device’s built-in modem to the secure Notal Health Cloud where the AI-based Notal OCT Analyzer (NOATM) will identify and quantify intraand subretinal fluid from each daily OCT scan. These images and temporal fluid volume trajectories will be shared with AsclepiX and investigators through the Notal Physician Portal. Further, patient compliance and remote support will be provided via the Notal Vision Diagnostic Clinic, which is the future provider of the Home OCT program. According to one of the study’s investigators Dr. Arshad M. Khanani, the clinical value and potential benefit of an
approach like this is even more crucial during the COVID-19 pandemic. “Remote OCT monitoring of patients with exudative retinal diseases in a regulatory clinical trial allows AsclepiX Therapeutics to capture critical data points while potentially reducing the burden of frequent office visits,” said Dr. Khanani, who is also the director of clinical research at Sierra Eye Associates in Reno, Nevada (USA). Indeed, the technology could set new standards for data enrichment and patient-centric conduct of clinical trials. Notal Vision CEO Kester Nahen, PhD, said they are excited to partner with AsclepiX Therapeutics and contribute their remote diagnostic services to the early phase clinical trial as “home OCT monitoring opens new opportunities to enrich clinical trial datasets with inter-visit disease and treatment response knowledge.”
| March/April 2021
WE’RE NO SOCIETY, WE’RE THE MEDIA.
e x p o . m e d i a m i c e . c o m 18-19 June 2021, 2-8 PM SGT