PIE Issue 26: The Lasers & Retina Issue

THE WORLD’S FIRST FUNKY OPHTHALMOLOGY MAGAZINE

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THE LASERS & RETINA ISSUE

MAY/JUNE 2023

piemagazine.org

Fifty years on, laser therapy remains a gold standard for some retinal treatment niches

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Letter to Readers

Of Lasers and the Retina Dear Readers, he retina, an essential component of our visual system, plays a crucial role in vision. Understanding how lasers interact with the T retina is of critical importance, given that the invention of lasers has revolutionized various fields, including medicine and technology.

The unique properties of lasers make them invaluable tools in numerous applications, particularly in the field of ophthalmology.

In the posterior segment of the eye, lasers have proven instrumental in the treatment of retinal diseases. Medical professionals and researchers have discovered various ways to utilize lasers in eye-related treatments. One such approach is laser therapy, which targets specific areas of the retina to seal leaky blood vessels, remove abnormal tissue, or create scar tissue to prevent further damage. This technique, known as photocoagulation, has become a cornerstone of retinal treatment and has significantly improved outcomes for patients.

However, it is essential to recognize the potential harm lasers can cause to delicate retinal tissue if used incorrectly or without appropriate safeguards. Thankfully, kudos to the industry’s dedication to this field, lasers have emerged as remarkable tools in ophthalmology, enabling precise diagnostics and effective treatments for retinal diseases.

Nevertheless, it is of utmost importance to acknowledge the potential dangers that lasers pose when used inappropriately. In this issue, we delve into the application of lasers in the treatment of retinal conditions, aiming to provide valuable insights and knowledge on this subject. By understanding the significance of proper laser use and the associated risks, ophthalmologists can ensure the well-being of their patients’ eyes.

We hope that the information presented in this issue proves valuable to your practice.

Best regards, Gloria D. Gamat

Chief Editor, Media MICE PIE, CAKE and COOKIE magazines

In This Issue...

magazine posterior segment • innovation • enlightenment

Matt Young CEO & Publisher Hannah Nguyen COO & CFO Gloria D. Gamat Chief Editor

Posterior Segment

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Subthreshold Lasers in Brief A new era of lasers for the treatment of retinal disorders

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Ode to Stem Cells… and South Park?

New study highlights how stem cells could restore retina function Customized Eye Care Combined with a T&E regimen, aflibercept promises to revolutionize treatment of retinal diseases

Cover Story

Mapet Poso Editor Maricel Salvador Graphic Designer Writers April Ingram Andrew Sweeney Brooke Herron Chow Ee-Tan Hazlin Hassan Matt Herman Tan Sher Lynn Contributors Dr. Sashwanthi Mohan Dr. Komal Agarwal Ruchi Ranga Customer Care International Business Development Brandon Winkeler Robert Anderson Adam Angrisanio Published by

Media MICE Pte. Ltd.

6001 Beach Road, #09-09 Golden Mile Tower, Singapore 199589 Tel: +65 8186 7677 Email: enquiry@mediamice.com www.mediaMICE.com

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Fifty years on, laser therapy remains a gold standard for some retinal treatment niches

Innovation

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What Lies Behind Your Eye Color German research highlights link between retinal health and eye pigment

Is AI the Answer?

With healthcare systems lagging, applications of AI in ophthalmic imaging show significant promise

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Enlightenment

Conference Highlights

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Devoted to Eye Care Dr. Barbara Parolini’s life-long commitment to vitreo-retinal health is evident in her illustrious career

What’s Next for RP? Laser treatment for retinitis pigmentosa — a beacon of hope for a progressively blinding disease

Tactics for Better Patient Outcomes Experts share data-backed updates for screening, diagnosis, and treatments of nAMD and PCV

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Elevating Vitreo-retinal Care in India Through educational initiatives, VRSI strives to prevent avoidable blindness

We are looking for eye docs who can contribute articles to PIE magazine. Interested? Let's talk!

Send us an email at editor@mediamice.com.

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Advisory Board Members

Dr. Alay S. Banker

Banker’s Retina Clinic and Laser Centre Ahmedabad, India

Prof. Gemmy Cheung

Singapore National Eye Centre (SNEC) Singapore

alay.banker@gmail.com

Dr. Barbara Parolini

gemmy.cheung.c.m@singhealth.com.sg

Prof. Mark Gillies

Eyecare Clinic Milan, Italy

University of Sydney Sydney, Australia

parolinibarbara@gmail.com

mark.gillies@sydney.edu.au

Dr. Hudson Nakamura

Bank of Goias Eye Foundation Goiânia, Brazil hudson.nakamura@gmail.com

Dr. Saad Waheeb

King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia saadwaheeb@hotmail.com

Society Friends

Arunodaya Charitable Trust (ACT)

Asia-Pacific Vitreo-retina Society

Orbis Singapore

Subthreshold Ophthalmic Laser Society

ASEAN Ophthalmology Society

He Eye Specialist Hospital

Retinawesome Retina &

Vitreo-Retinal Society - India

Asia-Pacific Academy of Ophthalmology

Ophthalmology Innovation Summit

Vitreous International

Russian Ophthalmology Society (ROS)

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PIE MAGAZINE | May/June 2023

Young Ophthalmologists Society of India ( YOSI )

World Ophthalmology Congress

LASER THERAPY

Posterior Segment

Subthreshold Lasers in Brief

A new era of lasers for the treatment of retinal disorders

by Dr. Sashwanthi Mohan and Dr. Komal Agarwal

Lasers are widely used for the treatment of retinal disorders. However, conventional laser photocoagulation produces visible thermal burns, which leads to destruction of the retinal tissue. Today, subthreshold laser is a category of photocoagulation method utilized to treat retinal or macular diseases that, unlike conventional laser treatment, provides therapeutic benefits without inducing visible laser scars in the treated area.

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sing subthreshold laser enables clinicians to minimize potential harm to the surrounding healthy tissues while still achieving the desired therapeutic outcomes. Thus, it is an alternative to conventional laser, especially for the treatment of central macular and foveal pathologies.

Conventional laser photocoagulation is a long-duration continuous photothermal laser that leads to coagulative necrosis of the photoreceptor-RPE choriocapillaris complex. This can cause collateral damage to the retina and complications, such as extensive scarring, choroidal neovascularisation, subretinal fibrosis, and visual field loss.

Subthreshold laser, on the other hand, does not cause any visible damage, preserves the retinal pigment epithelium (RPE) and photoreceptors, and allows for treatment close to the fovea. It does this by modulating heat-shock protein expression in the RPE and regulating cytokine expression without damage to the retinal tissue.

PIE MAGAZINE | May/June 2023

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Posterior Segment

LASER THERAPY

Different types and techniques Table 1 shows the different types of subthreshold lasers available today.1-4 Table 1. Types of Subthreshold Lasers

Type

Technique

Mechanism

Selective Retinal Therapy (SRT)

Short high-energy pulses of very short duration (< 5 microseconds), which leads to ‘microbubble formation’ that selectively targets RPE and spare surrounding tissues.

Selectively damages RPE cells leading to ‘retinal rejuvenation’ and preserves photoreceptors and neural tissue.

Micropulse Laser

Delivers laser energy using short pulses of duration (100-300 microseconds) in a repetitive fashion leading to an ‘on’ and ‘off’ time. The ratio of ‘on’ to ‘off’ is duty cycle. Microsecond pulses cause intracellular microbubbles around melanosomes.

Duty cycle below 100% and ‘off’ time use allows cool down time for the tissue and prevents retinal damage.

Selective Nanosecond Laser (SNL)

Ultra-short pulses of a few nanoseconds to selectively target RPE and spare surrounding tissues by formation of transient microbubbles around melanosomes. Shorter duty cycle than a micropulse laser.

Selectively damages RPE cells leading to ‘retinal rejuvenation’ and preserves photoreceptors and neural tissue. It delivers only 0.2% of energy per pulse compared to conventional laser.

Endpoint Management (EpM)

Rapid application of multiple laser spots array called pattern scanning with shorter pulse duration of 1030 microseconds using a 577 nm laser.

Provides visible titration endpoints, large number of spots can be placed in a fast manner, predefined patterns based on retinal landmarks.

Transpupillary Thermotherapy (TTT)

Low irradiance and long duration pulse of 1 minute applied over a large spot (0.5- 3 mm).

Useful for treating tumors of the retina and choroid.

Clinical indications and guidelines Subthreshold laser is indicated in the following guidelines5 and conditions: Central serous chorioretinopathy (CSCR), diabetic macular edema (DME), retinal vein occlusion (RVO)

associated macular edema (ME), agerelated macular degeneration (AMD), proliferative diabetic retinopathy (PDR), macular telangiectasia (MacTel)Type 2, and retinal and choroidal tumors (*TTT for these conditions).

The Subthreshold Ophthalmic Laser Society (SOLS) in 2022 has reported consensus guidelines (Table 2) for subthreshold laser application settings for DME and CSCR6 in an attempt to standardize care.

Table 2. The SOLS Guidelines for Subthreshold Laser Application Settings for DME and CSCR

Subthreshold Laser Settings

Diabetic Macular Edema

Central Serous Chorioretinopathy

Duty cycle

5%

5%

Pulse duration

200 ms

200 ms

Spot size

150–200 μm

100–200 μm

Spacing

No between spots

No

Titration

Yes

Yes

Titration power

50% of Threshold power

50% of Threshold power

Future developments and applications

treatment parameters and titration of power.

The evidence on the eligibility of patients requiring and responding to subthreshold laser is still developing.

A major amount of present evidence on subthreshold laser is based on small studies that are retrospective in nature with wide variability in

Evidence also suggests that retinal thickness can affect the efficacy of subthreshold laser in various retinal conditions. Such conflicting evidence on efficacy might be largely due to the variations and non-standardization in different clinical parameters used

by the clinicians in different clinical settings. With the latest guidelines by SOLS, we expect better evidence to support the use of subthreshold laser in a set clinical setting.

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PIE MAGAZINE | May/June 2023

Subthreshold laser is developing into a useful non-invasive adjunct for the treatment of macular and retinal diseases. Advantages of minimal to

no collateral damage, ease of repeatability, and noninvasiveness give the therapy significant potential to develop into a major therapeutic alternative or adjunct in certain retinal diseases.

References

RETINAL LASER THERAPY, REINVENTED

1. Ong J, Selvam A, Maltsev DS, Zhang X, Wu L, Chhablani J. Subthreshold laser systems: a narrative review of the current status and advancements for retinal diseases. Ann Eye Sci. 2022;7:15.

2. Chehade L, Chidlow G, Wood J, Casson RJ. Short-pulse duration retinal lasers: a review. Clin Exp Ophthalmol. 2016;44(8):714-721.

3. Sabal B, Teper S, Wylęgała E. Subthreshold Micropulse Laser for Diabetic Macular Edema: A Review. J Clin Med. 2022;12(1):274.

4. Li J, Paulus YM. Advances in Retinal Laser Therapy. Int J Ophthalmic Res. 2018;4(1):259-264.

XL_EASYRET_MOSAR_PUB_AN_230329

5. Brader HS, Young LH. Subthreshold Diode Micropulse Laser: A Review.

Semin Ophthalmol. 2016;31(1-2):30-39.

6. Chhablani J; SOLS (Subthreshold Ophthalmic Laser Society) writing committee. Subthreshold laser therapy guidelines for retinal diseases.

Eye (Lond). 2022;36(12):2234-2235.

Contributing Doctors Dr. Sashwanthi Mohan is a specialist ophthalmologist and vitreoretinal specialist at Medcare Eye Centre, Dubai. She completed her DNB Ophthalmology from L.V. Prasad Eye Institute in Hyderabad, India, and was awarded the Dr. G. Venkataswamy Gold Medal for Ophthalmology by the National Board of Examinations, followed by a vitreoretinal fellowship from Sankara Nethralaya, Chennai, where she was awarded as the best outgoing vitreoretinal fellow. She has a keen interest in research and has many peer-reviewed publications to her name. She is also interested in education and has an educational website called Ophthalmobytes. She is a fellow of the international council of Ophthalmology (FICO) and a member of the Royal College of Surgeons, Edinburgh (MRCS). sashu23@gmail.com

Dr. Komal Agarwal is an experienced vitreoretinal specialist in Prakash Netra Kendra in Lucknow, India, with a special interest in retinopathy of prematurity (ROP) and pediatric retinal disorders.

After completing her MBBS and post-graduation, she joined a fellowship program at the prestigious LV Prasad Eye Institute, India. She underwent further training in pediatric retinal disorders including ROP (both medical and surgical) during her fellowship.

She continues to work at LV Prasad Eye Institute as faculty in both medical and surgical retina. Dr. Agarwal is actively involved in clinical research. Her prime area of research interest is in pediatric retina and ROP. She has more than 45 research publications in peerreviewed journals, both national and international. She has also written five book chapters. Dr. Agarwal has presented her work at various national and international conferences.

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Posterior Segment

RETINA RESEARCH

Ode to Stem Cells… and South Park?

New study highlights how stem cells could restore retina function

by Andrew Sweeney

Stem cells might be controversial but they work, and their application in ophthalmology could herald tremendous benefits for patients. We examined one newly released study about how they could be used to heal the retina.

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ave you ever seen the American animated TV show South Park? The cartoon, which follows the exploits of four kids in the eponymous small Colorado town, is perhaps most famous for its free-flowing vulgarity and irreverence. However, don’t let this ostensibly juvenile approach fool you — the show is remarkable for its level of cultural and political insight, with its very rudeness allowing it to provide satirical commentary of a far higher

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degree of quality than any of its counterparts.

Take stem cells, for example. Years ago, during the early 2000s, stem cells had just begun to enter the consciousness of the general public, and the debate about their use, indeed — even their morality, was vicious. What was South Park’s approach? To take actor Christopher Reeve, a noted advocate for stem cell research after an accident left him paralyzed, and portray him gaining

PIE MAGAZINE | May/June 2023

superpowers from every ‘cell’ he imbibed while being opposed at every turn by fellow actor Gene Hackman.

Throughout the episode, the show’s main characters would appear and say something along the lines of “Yeah… let’s stay out of this one.”

In fact, that line would be the only appearance of all major characters throughout. It highlights how tempestuous the debate about stem cells was in those days, that the best joke South Park’s infamous creators could muster was that they wanted to stay out of the debate.

But in ophthalmology, we don’t want to stay out it Popular awareness of stem cells has improved since then as has

its acceptance by the medical community, and it’s not hard to understand why — they can provide remarkable benefits to patients.

That’s because they are selfrenewing cells that can differentiate into specialized cell types and can develop into multiple specialized cells in a specific tissue. Pluripotent stem cells, i.e., embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC), differentiate into cells of all three embryonic lineages.1

diabetic rats correlated with fewer signs of early vascular derangement characteristic of diabetic retinopathy.

Another reported that adiposestem-cell-derived exosomes ameliorated characteristic retinal degeneration following intraocular and subconjunctival administration among streptozotocin-induced diabetic rabbits.2

Since South Park’s commentary, it’s estimated that over one million patients worldwide have benefited from bone marrow transplantations performed for the treatment of leukemia, anemia, or immunodeficiencies. Skin stem cells are used to heal severe burns, while limbal stem cells can regenerate the damaged cornea. However, given their nature, there are numerous restrictions on ESCs, which is why adult, unipotent cells that differentiate only into one cell type are most commonly used.1

A study that could highlight how stem cells could be used to restore retinal function and eyesight, even partially, would, therefore, be a welcome development. Step forward a group of researchers based at Duke-NUS Medical School, the Singapore Eye Research Institute (both located in Singapore), and the Karolinska Institute in Stockholm, Sweden, who collectively thought: “Yeah, let’s NOT stay out of this one.” Their paper, Photoreceptor Laminin Drives Differentiation of Human Pluripotent Stem Cells to Photoreceptor Progenitors That Partially Restore Retina Function,3 examines the idea outlined above.

The existing and potential applications of stem cells in ophthalmology are remarkable, and it is no exaggeration to say that this research could revolutionize the field. According to one paper, applications in treating the cornea alone include chemical burns, corneal epitheliopathy, corneal laceration, dry eye disease, limbal stem cell deficiency, and keratoconus.

Keratoplasty and keratoprosthesis, invasive treatment options for visual impairment that can result in extensive corneal scarring, could be replaced by stem cell therapy, and studies involving grafted autologous rabbit adipose stem cells on a poly lactic-co-glycolic acid have provided promising results.2 However, the benefits of stem cells in ophthalmology go beyond the cornea.

There is evidence of their efficacy in retina treatment, too. One study found that the intravitreal injection of ADSCs in streptozotocin-induced

From rabbit to human retinas?

The team of researchers came up with a novel approach to cultivate stem cells by utilizing pure laminin proteins that play a crucial role in the natural growth of human retinas.

By exposing these cells to the laminins, they were able to guide their transformation into photoreceptor precursor cells that perform the crucial task of converting light into signals and transmitting them to the brain. Significant improvement in vision was subsequently observed in preclinical models when these cells were transplanted into damaged retinas.3 They observed that transplantation into 10 mice was able to protect the host photoreceptor outer nuclear layer (ONL) up to two weeks posttransplantation, as measured by fullfield electroretinogram. At four weeks post-transplantation, the engrafted

cells were found to survive, mature, and associate with the host’s rod bipolar cells.3 Visual behavioral assessment using the water maze swimming test demonstrated visual improvement in the cell-transplanted rodents.

At 20 weeks post-transplantation, the maturing engrafted cells were able to replace the loss of host ONL by extensive association with host bipolar cells and synapses.3 The researchers stated that by studying cell transcriptomic profiles and post-transplanted animal models, they demonstrated the absence of teratoma growth and partial improvement in vision. This suggested that the retina-specific laminin-based photoreceptor differentiation method may represent a safe approach for the treatment and management of retinal degenerative diseases.

They also found that this method may also be useful for studying the mechanistic pathways involved in the progression of macular degeneration, possibly leading to the development of alternative therapeutic interventions.3 This news represents a welcome development in the utilization of stem cells in ophthalmology and could provide sight-saving treatment — so kudos! That’s what you get when you decide not to stay out of a specific issue à la South Park. And we can only hope for more stem cell developments, whether they be in the retina, cornea, or other areas of ophthalmology.

In South Park, instead of saying that someone killed Kenny, maybe next time they’ll be amazed at someone saving his sight instead – all thanks to stem cells…

References 1. Dulak J, Szade K, Szade A, et al.

Adult Stem Cells: Hopes and Hypes of Regenerative Medicine. Acta A Biochim Pol. 2015;62(3):329-337.

2. Musa M, Zeppieri M, Enaholo ES, et al. Adipose Stem Cells in Modern-Day Ophthalmology. Clin Pract. 2023;13(1):230245.

3. Tay HG, Andre H, Guy CJ, et al.

Photoreceptor Laminin Drives the Differentiation of Human Pluripotent Stem Cells to Photoreceptor Progenitors That Partially Restore Retina Function. Mol. Ther.

2023;31(3):825-846.

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Posterior Segment

ANTI-VEGF THERAPY

Customized Eye Care Combined with a T&E regimen, aflibercept promises to revolutionize treatment of retinal diseases

by Hazlin Hassan

Separate, independent studies suggest that aflibercept has a longer half-life, greater potency, and better VEGF-A binding affinity than other available anti-VEGF agents. It also offers the flexibility to individualize treatment for patients with nAMD and DME, achieving and maintaining robust vision gains with treatment intervals of up to 16 weeks.

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16-week treat-and-extend (T&E) regimen in the use of aflibercept for retinal disease is possible and could revolutionize treatment options — this good news was presented during the Bayer-sponsored symposium entitled Patient-centric Approaches to Aflibercept Treatment in Retinal Disease at the 38th Asia-Pacific Academy of Ophthalmology Congress (APAO 2023), which recently took place in Kuala Lumpur, Malaysia.

Retinal diseases including neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) can cause irreversible vision loss, leading to blindness.

Aflibercept, developed by Bayer, is in the vascular endothelial growth factor-A (VEGF-A) and placental

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growth factor (PIGF) antagonist nAMD and DME. Furthermore, when class of medications. It works by combined with a T&E regimen, it has binding to VEGF receptors, stopping the potential to revolutionize the abnormal blood vessel growth and treatment of these conditions. leakage in the eyes, and reducing fluid accumulation in the retina.

Before the development of This decreases the risk of macular aflibercept, other anti-VEGF agents degeneration and improves vision such as bevacizumab (Avastin) and in patients with ranibizumab nAMD and DME. (Lucentis) were “Separate, independent in vitro and in vivo studies commonly used to treat Targeting suggest that aflibercept nAMD and the key DME. However, has a longer half-life and drivers these drugs greater binding affinity for had limitations, of retinal VEGF-A and PLGF than such as short diseases other available anti-VEGF duration of The effectiveness action, variable agents.” of aflibercept, efficacy, and also known as the need Assoc. Prof. Andrew Chang Eylea, has been for frequent shown to be injections. In superior compared to other anticontrast, aflibercept has a longer VEGF agents in the treatment of duration of action, with its half-life

P I E M A G A Z I N E | MMaayy/ /JJuunnee 22002233

being nearly twice as long as that of ranibizumab.

A recent in vitro study reported that aflibercept has a higher potency than brolucizumab and ranibizumab.

“Separate, independent in vitro and in vivo studies suggest that aflibercept has a longer half-life and greater binding affinity for VEGF-A and PLGF than other available antiVEGF agents,” said Assoc. Prof.

Andrew Chang from Sydney Eye Hospital, Sydney Retina Clinic, The University of Sydney, Australia.

Its estimated vitreous half-life is 9.1 to 11 days, while for brolucizumab it is 4.3 to 5.1 days, ranibizumab 7.2 days, bevacizumab 9.8 days, and faricimab 7.5 days.

Aflibercept is the only anti-VEGF agent that inhibits all VEGFR-1 and key VEGFR-2 ligands, including VEGF and PLGF, to target these drivers of retinal damage, Assoc. Prof. Andrew Chang noted.

Individualized patient care

weeks in patients with nAMD. “AntiVEGF treatment burden should be minimized without compromising the patient’s vision,” he said.

Aflibercept led to superior vision gains over two years compared with ranibizumab and bevacizumab in patients with baseline VA <69 letters.

According to the Asia-Pacific Vitreo-retina Society’s (APVRS) recommendations: “In the AsiaPacific region, many patients must commute vast distances to major treatment centers which may adversely affect treatment compliance. T&E retreatment criteria enable interval extension up to Q16 while allowing some stable residual fluid.”

One key challenge faced by patients with DME is that working-age patients have a complex comorbidity profile and a high burden of treatment. Diabetic patients with no DME face 14.9 healthcare visit days per year, while DME patients have 25.5 healthcare visit days per year.

APVRS recommends an interval extension of up to a maximum of 16 weeks with aflibercept, based on the ALTAIR and ARIES studies. This sees six fewer injections with aflibercept versus ranibizumab required to maintain vision gains in nAMD. In a network analysis, visual outcomes with aflibercept were superior to those reported with ranibizumab. T&E regimen showed significantly superior results over PRN, said Prof. Chaudhary.

Patients with nAMD do not benefit equally from anti-VEGF therapy, as there is a spectrum of different needs among patients. The effectiveness of aflibercept can be optimized when combined with a T&E regimen, which cuts the burden of frequent injections on patients.

In patients treated with aflibercept, there was a statistically significant difference indicating more favorable results for a T&E regimen over a PRN regimen.

In T&E, after an initial period of monthly injections to stabilize the disease, the interval between injections is gradually increased until the maximum interval is reached, after which the patient is monitored.

The VIVID and VISTA trials demonstrated the efficacy of aflibercept in improving visual acuity in patients with DME, and the treatment effect was maintained with a T&E regimen, said Assoc.

Prof. Voraporn Chaikitmongkol from Chiang Mai University, Thailand.

A pragmatic aflibercept T&E regimen offers the flexibility to achieve and maintain vision gains with intervals of Q4 to Q16, reducing treatment burden, said Prof. Varun Chaudhary from McMaster University, Canada.

Patients with polypoidal choroidal vasculopathy (PCV) can achieve and maintain long-term vision outcomes with aflibercept T&E, similar to patients with nAMD. Variation in VEGF suppression time between patients indicates a need for treatment individualization. The duration of VEGF-A suppression with aflibercept varies up to 16

The treatment of choice for DME

“Rapid vision gains achieved with early, intensive aflibercept treatment in year 1 were maintained over 148 weeks, with fewer injections in years 2 and 3,” he presented. Patients from VISTA maintained vision gains up to year 5 with continued aflibercept.

Guidelines from the European Society of Retina Specialists (EURETINA) state that aflibercept is the drug of choice in DME eyes with baseline BCVA below 69 letters, as it shows superiority to bevacizumab over two years and ranibizumab in the first year of treatment.

“Considering the treatment burden for diabetic patients with a complicated comorbidity profile is critical for disease management,” said Assoc. Prof. Chaikitmongkol.

Clinically meaningful vision gains are achievable with aflibercept regardless of baseline VA, but early, intensive treatment is important to maximize vision gains in all patients, she added.

Evidence from aflibercept clinical trials demonstrates the flexibility of individualized treatment from year 1, with robust vision gains and treatment intervals of up to 16 weeks. Assoc. Prof. Chaikitmongkol also noted that real-world studies show that RCT-like outcomes can be attained in clinical practice with aflibercept.

The flexibility to individualize treatments Outcomes with aflibercept are reproducible in the clinic, with 10 years of experience and safety data.

“Aflibercept offers the flexibility to individualize treatment for patients with nAMD and DME, achieving and maintaining robust vision gains with treatment intervals up to 16 weeks,” concluded Dr. Kenneth Fong from OasisEye Specialists, Malaysia.

Editor’s Note The 38th Asia-Pacific Academy of Ophthalmology Congress (APAO 2023) was held on February 23 to 26 in Kuala Lumpur, Malaysia. Reporting for this story took place during the event.

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Cover Story

Fifty years on, laser therapy remains a gold standard for some retinal treatment niches by April Ingram

Lasers in ophthalmology have recently celebrated their golden anniversary — and despite advancements in surgical techniques and intravitreal agents, lasers still firmly hold their seats at the table. So, how did laser manage to remain part of standard care for so long? The short answer: It is effective.

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t can be difficult to narrow down the coolest part about being a retina specialist.

Preventing blindness is, of course, the best, and having a toolbox that includes an array of surgical options and multiple avenues for drug delivery is awesome, too. Not to mention, “Oh, by the way, I use lasers!” is actually also a pretty impressive dinner party conversation starter.

Ophthalmologists have been using lasers for more than half a century now. And as our understanding of laser technology and the pathophysiology of retinopathies grows, laser is now less of a ‘turn and burn’ and more focused on safer, less intense stimulation of cells to restore function.

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Laser applications have advanced and evolved over the decades to address the collateral damage to surrounding retinal anatomy and other side effects. Changes have included shorter wavelength lasers, smaller spot sizes, shorter (micro) pulse duration and intensity, and the option of focal versus grid pattern technology.

The evolution of laser technology We had the opportunity to ask two prominent retina specialists to share how they have seen laser technology and its application evolve throughout their careers.

Dr. Jay Chhablani is a professor of ophthalmology and a vitreoretinal specialist at the University of Pittsburgh Eye Center, Pittsburgh, USA. Meanwhile, Dr. Igor Kozak is a vitreoretinal specialist and chief of retina service at Moorfields UAE in Abu Dhabi.

“There has been a tremendous amount of evolution in retinal laser technology — most importantly, the experimental and clinical work on sublethal and non-damaging approaches that include both subthreshold and micropulse laser techniques,” shared Dr. Kozak.

These approaches address the collateral damage of older laser versions and apply our greater understanding of retinal diseases.

“These provide therapeutic effects without causing tissue damage, which is characteristic of the classic threshold approach. In those, a thermal scar is produced in

the tissue, and that was believed effect may take longer and is more to convey a therapeutic effect. We difficult to measure objectively. know now that this may not be true Traditionally, physicians look at even though the pathophysiology optical coherence tomography of many retinal diseases is not fully (OCT) fluid and use it as a measure understood,” he noted. “Another of treatment outcome. With evolvement includes retinal laser sublethal techniques, the fluid delivery, which encompasses resolution may take longer. But splitting and it has been thus shortening observed that “There has been a of the laser the retinal tremendous amount beam in pattern function of evolution in retinal treatments and restores laser technology — eye-tracking in much quicker. retinal navigation This can be most importantly, the technology.” measured by experimental and visual acuity, clinical work on sublethal Dr. Chhablani color vision, and non-damaging couldn’t agree or contrast more, as he has sensitivity — approaches that include witnessed similar the latter are both subthreshold progression not routinely and micropulse laser and significant used in clinical techniques.” changes in practice,” retinal laser Dr. Kozak Dr. Igor Kozak applications explained. since his fellowship in 2007.

Although color vision or contrast sensitivity may be less commonly “It has gone from a single spot to assessed in the day-to-day clinic, multi-spot laser, and the newer when combined with improvement systems with features such as eye in visual acuity, these are the tracking, computer-based laser outcomes that are noticeable and planning, and visualization systems. valuable to patients.

Damage to the retina has been significantly reduced,” he enthused.

Where do lasers fit in the “Now we are using very efficient treatment paradigm? peripheral laser and subthreshold laser.”

For decades, lasers dominated the standard of care for many retinal disorders, but as intravitreal agents The benefits of laser were introduced, they were soon therapy adopted as the standard and a We also asked our experts to more conservative management explain the benefits of laser therapy strategy. in the management of current retinal disorders. Dr. Kozak noted “Lasers are still very useful in many that he no longer uses a classic diseases,” shared Dr. Chhablani. threshold laser photocoagulation, “For example, for central serous especially when treating the chorioretinopathy — for which we posterior pole disease due to its are doing subthreshold laser — untoward effects. quite often.”

“Instead, for the last decade, I have been using both retinal subthreshold pattern and micropulse treatments, which are much safer,” he shared. “The idea with these is to stimulate retinal pigment epithelial cells to resume their function, the lack of which is many times the cause of retinovascular diseases resulting in macular edema. The treatment

He added that laser is useful for treating diabetic retina, particularly in the non-responder cases of DME. “As for peripheral laser, panretinal photocoagulation (PRP) still holds a very good position in the management strategy, as well as for proliferative retinopathy, such as neovascularization associated with branch retinal vein occlusion (BRVO), neovascular glaucoma,

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Cover Story

and sickle cell retinopathy. There are many conditions where we continue to use laser,” he added.

However, despite the cool factor of using laser and its decade-long reputation as the workhorse of the retina, the popularity of intravitreal injection therapy cannot be denied — perhaps fueled by well-funded marketing teams and a media frenzy that now surrounds reported clinical trial data.

The truth behind the shift of attention away from laser therapy We wanted to know how the role of laser is currently acknowledged in clinical practice. Dr. Kozak doesn’t think we should be counting out laser anytime soon and shared his insights.

“The shift of attention away from laser to drug therapy has had a great impact on both basic research and clinical practice,” he said. “The lack of research funding and support for laser treatment has created the impression that retinal laser treatment is therapeutically inferior and is thus no longer relevant in the drug era — despite ample evidence to the contrary. Such evidence gets little attention because retinal laser treatment does not produce revenue for the companies that sponsor over 95% of all clinical trials in medicine and ophthalmology alike and support numerous practitioner investigators via clinical trials, all major ophthalmic journals, and professional societies,” he affirmed.

Looking at the real-world data, Dr. Kozak added: “Data for retinal laser treatment since the 1980s has relied on small clinical trials, retrospective studies, and real-world data studies that can be done at a far lower cost than large, randomized trials. The neglect of laser treatment is not because it is not useful or of no further scientific interest. Studies show that even conventional retinal photocoagulation remains indispensable even in the drug era and thus in wide use,” he continued.

Another key example has been shown in the treatment of

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retinopathy of prematurity, where laser photocoagulation has been a mainstay of treatment for decades, with a recent shift toward intravitreal anti-VEGF agents.

edema associated with venous occlusions. For many conditions, we tend to use laser as an adjunct therapy — so laser is not going anywhere. It will remain there, along with intravitreal injections.”

Although visual outcomes have been promising and intravitreal treatment A trusted, long-lasting is more easily accessible in some treatment regions, some studies have shown that the number of treatments and As Dr. Kozak noted, meetings and recurrence rates are higher with journals are filled with presentations anti-VEGF therapies. Additionally, of drug-centered trial data, enticing laser therapy clinicians with in these the promise “The rise in popularity infants does of improved of so many intravitreal not incur the outcomes. therapies has definitely same concerns associated with Dr. Kozak attempted to push antiangiogenic recognizes laser to the back seat. therapy in a the lure of new However, I still feel that developing treatments but laser plays an important infant. does not forget our old faithfuls. role — particularly for “The treatment Where laser things like central serous indications for chorioretinopathy, therapy laser therapy are where we can deliver game stays clear, however, it is subthreshold laser without always tempting to strong try novel therapies causing any damage, Dr. Chhablani and approaches,” especially when PDT is shares a similar he shared. “For not available.” perspective: that reason, the “The rise in armamentarium is – Dr. Jay Chhablani popularity of so wide and includes many intravitreal intravitreal therapies has definitely attempted pharmacotherapy, systemic to push laser to the back seat. treatment, or even topical/local However, I still feel that laser plays treatments for some. Many of these an important role — particularly have failed due to not reaching for things like central serous sufficient therapeutic levels in chorioretinopathy, where we can the target tissue and thus the deliver subthreshold laser without practitioners have returned to laser causing any damage, especially treatments to treat such conditions. when PDT is not available,” he said.

Another classical example is noncompliance with new medications Dr. Chhablani noted that intravitreal and returns to laser being a trusted, therapy cannot be used for all retinal long-lasting treatment.” diseases, and many patients remain inadequate or non-responder.

Dr. Chhablani shared similar “Subthreshold laser is playing a circumstances where laser remains very important role in CSC and the best treatment of choice, other diseases where we cannot despite the approval of intravitreal do intravitreal therapy or when therapy. “There are patients who intravitreal therapy alone is not are not compliant with regular sufficient,” he enthused. intravitreal therapy for many reasons. They may simply do not As an example, he continued: “Many remember their appointments, there advanced proliferative, diabetic may also be insurance coverage retinopathy patients and other challenges, or those that cannot proliferative retinal diseases benefit manage the financial burden,” from laser therapy. It also plays a he explained. “As well, many of valuable role for the treatment of these patients also have systemic diabetic macular edema and macular diseases, which means multiple

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specialist appointments, and transportation or arranging for family members to bring them is difficult.

When we recognize these challenges in our patients, where intravitreal therapies cannot be provided on a monthly basis, consistently, we tend to offer more long-term treatment options, such as laser.”

He shared other common examples: “Proliferative diabetic retinopathy and diabetic macular edema, as well as venous occlusions.”

Often the first-line therapy Finally, we wanted to know where laser fits in the vitreoretinal toolbox today. As Dr. Chhablani previously noted, “For central serous chorioretinopathy, laser is certainly the first-line treatment. We do focal, conventional laser treatment, as well as subthreshold laser and PDT.” Laser also has a stronghold in the management of the diabetic retina, as Dr. Chhablani shared: “For me, if I see an eye with proliferative diabetic retinopathy, first-line treatment is still a laser, panretinal photocoagulation. As well, if I see any neovascularization or other proliferative diseases, I would do laser as first-line.”

Similarly, Dr. Kozak shared that laser is still very much part of his treatment toolbox, often in a synergistic way. “While the firstline therapy for the majority of central retinovascular diseases is anti-angiogenic therapy, a large portion of primary non-responders will have laser supplementation,” he said. “This is done exclusively using sublethal approaches even if they need to be repeated. Such approaches are non-damaging and often act synergistically with other therapies. I then carefully assess functional outcome, which influences my follow-up and retreatment if needed.”

“Where the injections are not doing a great job, or we cannot afford to give injections or we are not able to do injections every month — in those situations, laser fits into a second line and as a combination of treatments,” shared Dr. Chhablani.

“As well, for treatment-resistant retinal conditions, we tend to use laser as part of combination therapy, including peripheral ischemia for venous occlusions or even peripheral ischemia for diabetic macular edema.”

Dr. Kozak described the value of threshold laser for peripheral

Contributing Doctors Dr. Jay Chhablani, MD, is a vitreoretina surgeon at the University of Pittsburgh Eye Center, Pittsburgh, USA. He leads the “Choroid Analysis and Research (CAR) Lab” at the University of Pittsburgh, which focuses on computational as well as biological research in the field of choroid. He completed a clinical vitreoretina fellowship from Sankara Nethralaya, Chennai, India, and was an International Council of Ophthalmology (ICO) fellow at Jules Gonin Eye Hospital, Switzerland, in 2009. He was a clinical instructor at the Jacobs Retina Center at Shiley Eye Center, University of California, San Diego, USA, from 2010 to 2012, before joining the faculty at LV Prasad Eye Institute, Hyderabad, India, from 2012 to 2019. His areas of interest are macular disorders and recent imaging techniques.

He has published more than 500 articles in peer-reviewed journals with a focus on choroid.

He is the editor of the books “Choroidal Disorders”, “Central Serous Chorioretinopathy” and “Choroidal Neovascularization”.

He is on the reviewing boards of high-impact journals, including Science Translational Medicine and Lancet. He is also on the editorial board of several journals, including the American Journal of Ophthalmology. He is a member of the Macula Society and of various committees in international societies, including the American Academy of Ophthalmology. He has won several national and international awards and delivered the inaugural Ian Constable lecture at the Asia-Pacific Vitreo-Retina Society in 2016. He received

retinal diseases: “Such as sealing retinal breaks or holes or ablating ischemic areas of the retina that would produce secondary damage to the eye. Similarly, during retinal surgery, I use endolaser to address the pathology leading to conditions such as retinal detachment or severe diabetic retinopathy,” he concluded.

Inaugural Namperumalsamy Young Researcher Award in 2018, presented by the Vitreo-Retina Society of India. jay.chhablani@gmail.com

Dr. Igor Kozak, MD, PhD, MAS, is a consultant ophthalmologist, specialist in vitreoretinal surgery, medical retina, and uveitis, and chief of Retina Service at Moorfields, UAE in Abu Dhabi. Dr. Kozak is a renowned specialist in the whole range of vitreoretinal surgical procedures, including pediatric ophthalmic surgery. He undertakes advanced surgical procedures and has pioneered some retinal laser techniques. Dr. Kozak undertook his medical and ophthalmology training in Slovakia, before a Vitreoretinal Clinical Rotation at Moorfields Eye Hospital in London, and Fellowships in corneal immunology, vitreoretinal, and uveitis in the USA. He has also practiced and researched at leading institutions in the Kingdom of Saudi Arabia. He has extensively researched, undertaken clinical trials, published, and lectured around his specialist areas of interest. Dr. Kozak is boardcertified in ophthalmology and holds a number of supplementary specialty certificates. He is the recipient of several academic awards and honors, and a member of leading professional bodies in the US and Europe. In addition to his medical roles, Dr. Kozak has been actively involved in public service programs and education. igor.kozak@moorfields.ae

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Innovation

OPHTHALMIC IMAGING

Is AI

the Answer?

With healthcare systems lagging, applications of AI in ophthalmic imaging show significant promise

by Tan Sher Lynn

Renowned ophthalmologist and expert in imaging and machine learning Dr. Suber Huang talked to us about how artificial intelligence is set to transform the field of ophthalmic imaging like never before.

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ver the past few years, artificial intelligence (AI) has been a force that is permeating all aspects of our lives, brought on by the digital era and accelerated by the COVID-19 pandemic.1 In ophthalmology, deep learning has been widely used in imaging, such as fundus photographs, optical coherence tomography (OCT), and visual fields — achieving robust classification performance in the detection of diseases like diabetic retinopathy and retinopathy of prematurity, glaucoma-like disc, macular edema, and agerelated macular degeneration.2

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AI in Ophthalmology: An unstoppable revolution “Imaging in ophthalmology is undergoing a revolution in all facets,” started Dr. Suber Huang, founder and CEO of Future Vision Foundation (Ohio, USA).

“On a sophisticated level, AI can do repeated tasks quickly and repetitively with a kind of certainty that’s difficult (for humans) to do. And at the highest level is the fact that it can learn from its algorithm, either from a dataset that we already know, or potentially educate itself as we go on.”

“While there used to be just fundus photographs, clinical exams, and fluorescence angiography, there are now many kinds of imaging modalities, such as OCT and its different kinds, including intraoperative OCT, as well as multimodal imaging,” he shared.

He added that combining these imaging modalities with AI and machine learning would allow us not only to look into the structure (of the eye) but also potentially its function. “Also, federated machine learning is a very important concept in AI, where we can use lots and lots of data and have findings and insights that we would never have before. By aggregating lots of data potentially from all over the world, such as the natural history of a million patients, we can have a better view of things that we can never do before,” he continued.

“On a sophisticated level, AI can do repeated tasks quickly and

too many patients. So we are looking for ways to increase the efficiency of medical care here,” he said.

And AI may just be the answer. By using AI to do repetitive tasks such as screening, physicians will not be put out of jobs, but every patient they see will potentially be presented at the right time required to save their vision, noted Dr. Huang.

repetitively with a kind of certainty that’s difficult (for humans) to do. And at the highest level is the fact that it can learn from its algorithm, either from a dataset that we already know, or potentially educate itself as we go on,” he explained.

The importance of data sharing While Dr. Huang has many notable achievements under his belt, the most historic one is the Retina Image Bank, a vast open-access library of more than 25,000 unique and downloadable retina images.

comprehensive open-access site,” he said proudly.

He also stressed the importance of data sharing between AI platforms, which could facilitate more accurate models and results. “Market forces allow companies to address an unmet need to thrive, but the bigger picture is, for instance, to share data that otherwise is generated but lost. For example, if a clinical trial succeeds, that data is published. But if a study is extremely well done but doesn’t meet its endpoint, that data is sequestered and lost,” he noted.

“A work which I am most proud of is the Retina Image Bank platform. It is “To have a robust AI system, you a program of the American Society would really like to have a million of Retina images that Specialists, reflect the whole “To have a robust AI which I started world. And it is system, you would really approximately important to 10 years ago,” devise systems like to have a million he shared. that can link images that reflect the “Initially, it works and share data as a repository across platforms whole world. And it is of educational all over the important to devise material, fundus world,” he systems that can link photographs, emphasized. and all kinds and share data across of things AI in the platforms all over the related to the Asia-Pacific world.” retina. Today, it is growing Dr. Huang very well, not described the surprisingly. It took about three years Asia-Pacific region as a growing and to get to a million page views. And very important region in the world, this summer, we passed 3 million as it houses the majority of the page views. It’s been used in over population worldwide. “However, the 181 of 183 identified countries in the healthcare systems in the region are world, and we have 40 thousand lagging behind, and every healthcare hits per month. The important thing system is under financial constraint. is, it is the world’s largest, most In short, there are too few doctors for

“I think there are opportunities all around for innovation, which will make things better and easier — just as each version of our cell phone gets a little bit better and a little bit easier to use. But the real major innovation is unpredictable, and we don’t know when that will come,” he mused.

References 1. Benet D, Pellicer-Valero OJ. Artificial intelligence: the unstoppable revolution in ophthalmology. Surv Ophthalmol.

2022;67(1):252-270.

2. Ting DSW, Pasquale LR, Peng L, et al.

Artificial intelligence and deep learning in ophthalmology. Br J Ophthalmol.

2019;103(2):167-175.

Contributing Doctor Dr. Suber Huang is the CEO of the Retina Center of Ohio and a voluntary assistant clinical professor of ophthalmology at Bascom Palmer Eye Institute, University of Miami, Florida, USA. He is also the CEO of the Future Vision Foundation, whose mission celebrates breakthrough vision research through powerful documentaries of discovery, impact, and hope. He created the Future Vision Forum to bring visionary leaders in basic, translational, and clinical research together to seek new directions that accelerate discovery and innovation. Dr. Huang has over 25 years of experience as a retina specialist and has held various leadership positions, such as being the president of the American Society of Retina Specialists. Also, he has received numerous awards, including the “Top Doctors” and “Best Doctors in America” awards each year since 2003.

DrHuang.RCO@gmail.com

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Innovation

RETINA RESEARCH

What Lies Behind Your Eye Color German research highlights link between retinal health and eye pigment

by Andrew Sweeney

The Kynurenine pathway’s role in determining an individual’s retinal health is becoming clearer, and it goes to show that someone’s ocular color pigment plays a bigger role than just assumed personal characteristics.

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id you know that according to the ancient Greeks, blue eyes were seen as a sign of cowardly, barbaric nature, as opposed to the more common light brown of old Athens and Sparta?

Of course, we’re also familiar with a different interpretation of the significance of this shade of color as propagated by a certain 20thcentury Austrian political activist…

Thankfully, such nonsense doesn’t have much currency in the modern day.

Throughout human history, cultures have ascribed values, characteristics, and important associations with eye color for various pseudo-scientific reasons. Could the same issue have real ramifications for our ocular health, too?

According to a group of researchers based at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, the color of one’s eye could well have a considerable impact on retinal health.

Their recently published research paper, Modulating the Kynurenine Pathway or Sequestering Toxic 3-hydroxykynurenine Protects the Retina From Light-Induced Damage in Drosophila,* examines the Kynurenine pathway’s (KP) role as an evolutionary conserved metabolic pathway that regulates a variety of biological processes. Comprised of a number of chemical elements within cells, the pathway has a considerable influence on much of the body’s key functions.

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Flies and humans — so much in common According to the researchers, as it turns out… humans and flies have a lot in common.

The research examines retinal homeostasis in the context of light stress in Drosophila melanogaster cinnabar, cardinal, and scarlet, which are fly genes that encode different steps in the KP. Yes, you read that right, fly genes!

As it turns out, the KP is preserved in flies as much as it is in humans, allowing scientists to extrapolate their research results and postulate a similar conclusion for humans.

Furthermore, in both flies and humans, the severity of a mutant phenotype/symptoms in individuals carrying the same mutation can be highly variable, ranging from complete neuronal degeneration to weaker manifestations of a given disease phenotype.* The researchers from Dresden proposed that given that the KP not only participates in brown pigment formation but is also part of metabolic processes in cells, the role of Drosophila w (found in the fruit fly and was the first sex-linked mutation discovered) in predisposing eyes to degeneration is linked to an imbalance in some KP metabolites, rather than to its role in pigment biosynthesis — and hence shielding the eye from excess light.

They pointed to the fact that mutations in Drosophila w, which lack all pigments and make the eyes white in color, modulate retinal degeneration in flies expressing the human Tau protein to back up their proposal. To investigate further, they examined genetic interactions, biochemical analysis of metabolites, and dietary intervention.

By devising a technique for analyzing the biochemical makeup of Kynurenine pathway metabolites, the researchers were able to correlate varying metabolite levels with the overall health status of the retina — and it should be noted that this represented a novel technique. They subsequently discovered that a specific metabolite, 3-hydroxykynurenine (3OH-K), has a detrimental effect on the retina.

Furthermore, they were able to demonstrate that the extent of degeneration is impacted by the equilibrium between harmful 3OH-K and beneficial metabolites, such as Kynurenic acid (KYNA).

the ratio of different metabolites and their respective locations and functions in order to address disorders associated with impaired KP activity, as seen in a range of neurodegenerative conditions.

Clues to retinal health lie in your genes

Finally, the German scientists shared that the increase of free 3OH-K is clearly detrimental to retinal health, and that they had unraveled the importance of compartmentalization of the KP metabolites as a protective mechanism.

The researchers also administered two of these metabolites to normal (non-mutant) flies and observed that 3OH-K amplified stress-induced damage to the retina, whereas KYNA prevented stress-related damage to the retina. This finding implies that the ratio of Kynurenine pathway metabolites can be modified to enhance retinal health in specific circumstances. The researchers also found that targeting these four genes, which represent four distinct stages within the pathway, affects not only the concentration of 3OH-K itself, but also its location in the cell and its accessibility in subsequent reactions, highlighting its significance for retinal health.

In their concluding remarks, the researchers stated that their study demonstrated the significance of the KP not just for pigment production, but also for maintaining healthy retinas via the roles of specific metabolites. They added that in the future, therapeutic approaches targeting the KP should consider

Therefore, we can say that the pigmentation that determines your eye color plays a role in the health of your retina. This is a fascinating area of study, and we look forward to hearing more about it in the future.

Who knows, maybe there was an ancient Greek philosopher who postulated that eye pigment has more to do with retinal health and less to do with baby blues making you more likely to run from a fight.

We thank the German researchers and their humble fly volunteers for their contribution to medical science and retinal health.

Reference * Hebbar S, Traikov S, Hälsig C, Knust E. Modulating the Kynurenine pathway or sequestering toxic 3-hydroxykynurenine protects the retina from light-induced damage in Drosophila. PLoS Genet.

2023;19(3):e1010644.

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Innovation

LASER TREATMENT

What’s Next for RP?

Laser treatment for retinitis pigmentosa — a beacon of hope for a progressively blinding disease by Tan Sher Lynn To date, there’s no cure for retinitis pigmentosa (RP), an inherited disease that can lead to blindness. However, recent studies on retinal lasers and RP showed promising results in slowing disease progression and improving function.

R

etinitis pigmentosa is a debilitating inherited eye disease for which effective treatment is not yet known, despite advances in drugs, genetics, and immunotherapy.1 In fact, it is the fourth leading cause of blindness in the world.2 Nevertheless, all hope is not lost.

It was discovered that the use of retinal lasers may help preserve sight in patients with photoreceptor degeneration, as demonstrated by studies on animals and humans.

A review on laser treatment for RP found six studies involving animal models and three studies involving human subjects in the PubMed database.3

Of mice…

Among them, a 2019 study4 published in the Translational Vision Science & Technology journal found that retinal laser therapy preserved photoreceptors in rats with Mer tyrosine kinase receptor (MERTK)related RP.

of Surgeons (RCS) rats, while the left eyes were used as control. Rats were monitored for six months after treatment using electroretinography, optical coherence tomography, and histology.

The authors found that photocoagulation led to the preservation of photoreceptors on a long-term basis, with the degree of the benefit dependent on the laser pattern density. Pattern photocoagulation of about 15% of the photoreceptors (eyes treated with a 1.5 spot size spacing) demonstrated the best morphologic and functional preservation during the six-month follow-up. Meanwhile, SRT-treated eyes demonstrated short-term morphologic preservation, but no functional benefit. Finally, NRTtreated eyes did not show any observable preservation benefit from the treatment.

… And men

In the study, the authors used three modalities, including photocoagulation with various pattern densities, selective RPE therapy (SRT), and non-damaging retinal therapy (NRT).

Meanwhile, a 2018 study5 published in the peer-reviewed journal Eye examined the effect of subthreshold diode micropulse laser (SDM) on pattern electroretinography (PERG) and visual function in RP. Twenty-six eyes of 15 patients were included, of which seven were male and eight were female, aged between 16 and 69 years.

Laser treatments were performed on the right eyes of the Royal College

Each eye was evaluated by PERG one week prior, and one month

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after, SDM treatment, which showed that retinal function improved by all indices. Meanwhile, omnifield resolution perimetry (ORP) testing was performed on 23/26 eyes, which showed that 17 (81%) eyes were improved by all measures compared to control eyes after SDM treatment.

The study concluded that SDM improved mesopic visual fields and mesopic and photopic visual acuity in RP regardless of the underlying genomics. As such, SDM may slow progression and reduce visual loss related to RP. It also suggested that new RP treatments be evaluated by confirmation of improved retinal electrophysiology function.

Close, but not there yet Although there’s a promising role for retinal lasers in the treatment of RP, currently, there isn’t enough data to support laser treatment as a standard procedure to treat RP in humans.

Retinal lasers should be investigated more extensively in clinical trials, with the hope that one day this modality could be widely used to benefit millions of people affected by RP worldwide.

References 1. Sacchetti M, Mantelli F, Merlo D, Lambiase A. Systematic review of randomized clinical trials on safety and efficacy of pharmacological and nonpharmacological treatments for retinitis pigmentosa. J Ophthalmol.

2015;2015:737053.

2. Bourne RR, Stevens GA, White RA. et al.

Vision Loss Expert Group Causes of vision loss worldwide, 1990-2010: a systematic analysis. Lancet Glob Health. 2013;1:339349.

3. Gawęcki M. Laser treatment in retinitis pigmentosa — a review. Lasers Med Sci. 2020;35(8):1663-1670.

4. Kang S, Lorach H, Bhuckory MB, Quan Y, Dalal R, Palanker D. Retinal Laser Therapy Preserves Photoreceptors in a Rodent Model of MERTK-Related Retinitis Pigmentosa. Transl Vis Sci Technol. 2019;8(4):19.

5. Luttrull JK. Improved retinal and visual function following panmacular subthreshold diode micropulse laser for retinitis pigmentosa.

Eye (Lond). 2018;32(6):1099-1110.

APVRS 2023

Hong Kong, China Hong Kong Convention and Exhibition Centre

15 - 17 Dec, 2023

The 16th Asia-Pacific Vitreo-retina Society (APVRS) Congress

PIE MAGAZINE | May/June 2023

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Enlightenment

WOMEN IN OPHTHALMOLOGY

Devoted to Eye Care Dr. Barbara Parolini’s life-long commitment to vitreo-retinal health is evident in her illustrious career

by Chow Ee-Tan

Dr. Barbara Parolini is recognized as one of the leading authorities in the field of vitreo-retinal surgery, not only in her native country of Italy but also internationally. A force to be reckoned with in ophthalmology, she is passionate and committed to changing the field of vitreo-retina for the better.

S

ince she started her practice in 1997, Dr. Barbara Parolini, director of Vitreo-Retinal Service at Eyecare Clinic in Brescia, Italy, has done 15,000 eye surgeries — mainly vitreo-retinal cases as well as cataract, cornea, glaucoma, and refractive (phakic lenses and excimer laser).

She has performed live surgeries in Italy and abroad, more specifically at the Frankfurt Retina Meeting, the Portuguese VR Society, FLORetina 2019, and EVRS. She has published 70 peer-reviewed manuscripts, five book chapters, and one e-book on vitreo-retinal techniques (released in 2018) for surgical training.

“My main area of expertise concentrates on complex cases of submacular surgery, high myopia, as well as eye reconstruction

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fellowship in basic science at UCSF (San Francisco, USA) and UMDNJ (Newark, USA), studying retinal pigment epithelium transplantation in vitro and in vivo. Between 1997 and 1998, she was the director of Clinical Studies for the FDA for the Medjet Company in Edison, USA.

Heeding a strong calling After undergoing both scientific and humanistic studies during high school, Dr. Parolini entered medical school. “I was passionate about everything. But it was when I became an intern in ophthalmology, and more specifically when I looked through the microscope, that I fell in love with what I was seeing and thought I could dedicate my entire life studying the eye — a micromacro universe.”

after trauma,” shared Dr. Parolini.

“However, I started my initial practice by opening a refractive “I was passionate about surgery center everything. But it was in north Italy, one of the firsts when I became an intern in the country. in ophthalmology, and From being a refractive more specifically when specialist, I I looked through the switched to microscope, that I fell retina, while still performing in love with what I was cataract seeing and thought I surgeries.”

During residency, she thought there were too many unmet needs in retina. “I was fascinated by what could be seen (and what still could not be seen) through could dedicate my entire the microscope Dr. Parolini and the imaging life studying the eye — a graduated options. I was micro-macro universe.” from Italy caught by the Medical School challenges of the with Laude in 1993 and obtained unknown and undone, by the dream a diploma in ophthalmology in of offering new sights to the blind.

1997. She then took a postdoctoral Retina was and still is full of enigmas

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that should be solved,” she enthused.

the technique since then.

Dr. Parolini has maintained an “In 2020, I decided that instead of interest in the retina and was happy focusing on building a new medical to pursue the device, it was transplantation smarter to “In 2020, I decided that of retinal concentrate on pigment a commercially instead of focusing on epithelium (RPE) available building a new medical and choroid in product. I device, it was smarter vivo, changing focused then on the surgical the ALJ product to concentrate on a technique to and decided commercially available optimize results. to modify the shape and product. I focused then “I discovered insert it with an on the ALJ product that easier surgical and decided to modify perfluorocarbon technique,” she liquid (PFCL) shared. the shape and insert it could be used with an easier surgical under the retina Dr. Parolini has technique.” to stabilize the been working graft of choroid in hospitals and that it was in Italy, but indeed indispensable to avoid the most of the time, she has been in rolling and floating of the graft itself,” private practice. She had also been she shared. “My team and I also a consultant surgeon in Kuwait, discovered that the choroid could be working there one week per month cut without major bleeding, and that from 2016 to 2020. the patch of choroid could integrate and we could save the macula.”

“I wanted to leave room for my professional expansion. I was head For the studies on lamellar macular of department in a hospital in Italy holes (LMH), she discovered during for more than one year, but I did not a surgery in 2008 that there were enjoy it. I was losing contact with two different epiretinal proliferations patients and studies,” she continued.

(ERP) connected to the LMH. But even outside of the university, “I arranged a new group study in she has been working in ‘academic Munich led by Christos Haritoglou, in style’ — collecting data, teaching order to make a correlation between and training other colleagues, and the optical coherence tomography lecturing at meetings in Italy and (OCT) image, the surgical aspect of countries around the world. the tissue and the histological, and immunohistochemical composition of More studies and data the membranes,” she continued.

The study, published in Investigative Ophthalmology & Visual Science (IOVS) in 2011, led to a huge step forward in the comprehension of LMH and the types of epiretinal membrane (ERM) associated with it.

Honing her surgical techniques At the same time, Dr. Parolini was studying how to buckle the macula in high myopes without suturing the buckle behind the macula, by trying many home/self-made devices. She presented her model at the Heatam meeting in 2009 for the first time in Amsterdam and has been improving

buckle; and clinical researches on intraoperative OCT and widefield OCT/OCT-A. Dr. Parolini’s other focus since 2007 has also been the transplantation of autologous choroids. She explored the benefits of transplantation of autologous retina and the combination of the two surgeries, and discovered that the retina can do much more than we think in adults and children.

Furthermore, since 2008, she has been dedicating her studies to myopic traction maculopathy (MTM).

“MTM patients have always been considered as patients destined to blindness. The treatment had not been improved because the etiopathogenesis had not been totally understood,” she explained.

She has also studied the natural history of the disease by collecting hundreds of OCT scans from her

collection: The way to work and grow Here is a doctor who believes in collecting all her data. Dr. Parolini constantly analyzes what she does in order to improve and publish new discoveries — she considers it the only way to work and grow.

Some of her most meaningful achievements include long-term data on the results of choroidal autologous transplant for maculopathies; the description of the two epiretinal proliferations associated with LMH; the description of myopic traction maculopathy staging system, which is now widely used; the creation of the surgical strategy of macular PPI IEE M MAAGGAAZZI INNEE | | M a y / J u n e 2 0 2 3

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Enlightenment

WOMEN IN OPHTHALMOLOGY

patients (their actual and their past OCT). She personally viewed each one of them, in order to reconstruct and understand the evolution of the disease. That study allowed her to find a schematic progression of the disease, which has been collected in one single table: The MTM staging system table.

Dr. Parolini has collected many publications on the new staging system of MTM, which is now internationally validated. She then studied the best treatment per each stage of the disease and developed a new model of macular buckle to treat the macular detachment secondary to MTM. “I channeled my energy and time into making the surgical strategy easier in order to enlarge the indications and use of the MB. I hope this year I will be able to release a new model which will be shortly presented,” she shared.

Dr. Parolini has a wishlist that she hopes will be realized one day. “I would love to see us as a large community sharing big data easily on multiple subjects in a safe and intelligent way. I hope we can find a cure for genetic mutations and have easier access to research and development of new ideas and devices,” she said wishfully.

Embracing the ups and downs One thing’s for sure, Dr. Parolini has faced many challenges throughout her career, but they did not set her back. “I still feel a sense of guilt and frustration when I cannot save the sight of a patient,” she confessed.

She says it can be frustrating when she faces difficulties against bureaucracy and economics. “For example, I know how to build the perfect macular buckle, but to do so I would have to undergo a very long and expensive study. The final product would cost so much that it would not be suitable for the market,” she said expressing her disappointment.

“Also, it can be challenging to keep up with patients and with academic duties. I have many meetings as an organizer, presenter, and moderator, and I do a lot of traveling, studying,

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and publishing. I am in the process of building a practice with coworkers,” she shared.

However, it is most rewarding when she knows she has done something that touches others’ lives. “[It feels good] when I hear my patients tell me that they are not afraid anymore because they know I am there to do anything I can to save their sights,” she shared.

Dr. Parolini also finds satisfaction in helping and mentoring colleagues.

“I am happy knowing that I am able to offer advice to younger colleagues. It is gratifying to know that somewhere on the other side of the planet, there are colleagues who are doing something because they heard me lecturing [about it], or read a paper I wrote,” she noted.

Her family, her world Dr. Parolini’s family means the world to her. She is married to Giovanni, a radiologist, and they have two daughters: Sofia, 23, and Sara, 18.

“My husband has always been very supportive,” she shared. “We have always split our time equally with our girls when needed. Our girls have grown extremely independent since childhood, not only understanding they have to be responsible for their behavior and choices, but also knowing they could always count on our guidance.”

Traveling is also a big part of their family life. “We traveled the world together because I had the luck and honor to be invited as keynote speaker in many different countries.

Both our girls very much enjoyed traveling with us, which allowed us to build lifelong memories together,” she shared.

Dr. Parolini considers herself lucky that her daughters consider her and her husband not only as their role models but also their best friends.

“This is our greatest achievement,” she beamed. “I still remember the time they told me, ‘Mom, we don’t know what we want to do in our lives, but whatever we do we want to do it with the same passion you have for your work.’”

Ultimately, Dr. Parolini has been

P I E M A G A Z I N E | MMaayy/ /JJuunnee 22002233

inspired by life itself. “I am happy to tell you that I am still alive after fighting a bad retroperitoneal liposarcoma removed with major surgery in 2011 and treated with chemo and radiotherapy,” she earnestly shared. “I had some health issues related to that the year after, but again I am here to tell the story!”

“I don’t mean to sound presumptuous, but I am driven by the desire to leave a trace of me in history. I believe this is what makes us immortal,” she concluded.

Contributing Doctor Born in Verona, Italy, Dr. Barbara Parolini is an ophthalmic surgeon.

She graduated from Medical School in Italy with Laude in 1993 and obtained a diploma in Ophthalmology in 1997. She has undertaken a postdoctoral fellowship at UCSF (San Francisco, USA) and UMDNJ (Newark, USA), on retinal pigment epithelium transplantation in 1994-1995 and 1997-1998. She was the director of Clinical Studies for FDA for the Medjet Company, in Edison, USA, from 1997 to 1998. Her expertise is in complex cases of submacular surgery, diabetic retinopathy, and high myopia, as well as eye reconstruction after trauma. She is a tutor of Bremen EVRS VitreoRetinal School and Thessaloniki VitreoRetinal School, and has performed live surgeries in Italy and abroad; of note, at the Frankfurt Retina Meeting, the Portuguese VR Society, and FLORetina 2019. She serves as a reviewer of various peer reviewedjournals including Graefe’s Archives of Ophthalmology, Retinal Journal, European Journal of Ophthalmology, British Medical Journal of Ophthalmology, and others. Since 2016, she has been serving as vice president of the European VitreoRetina Society, and since 2020, a board member for Retina World Congress leading the RWC-Global Research Group.

She obtained a patent of a model of macular buckle and a kit for episcleral surgery. On June 16, 2023, she due to receive the DOC Retina Science Award. parolinibarbara@gmail.com

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Enlightenment

OPHTHALMIC EDUCATION

Elevating Vitreo-retinal Care in India Through educational initiatives, VRSI strives to prevent avoidable blindness

by Brooke Herron

As one of the largest retina societies in the world, the Vitreo-Retinal Society of India (VRSI) has rightly earned its reputation as a thought leader in the field — thanks to its high-quality annual conferences, dedication to increasing public awareness for retinal diseases, and contributions to scientific literature.

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ver the past three decades, VRSI has grown exponentially. Founded in 1992 by 20 dedicated vitreo-retinal specialists, the society has now more than 1,500 members across India — including 90% of the country’s actively practicing vitreoretinal specialists.

The society is managed by an elected executive committee: President Dr. N. S. Muralidhar, Vice President Dr. R.

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Kim, Scientific Convenor Dr. Mahesh P. Shanmugam, General Secretary Dr. Manisha Agarwal, and Treasurer Dr. Prashant Bawankule, along with other executive members.

Together, the executive committee and its members work to elevate the standard of vitreo-retinal care and resources in India, focusing on two main areas: Public health and continuing education.

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Addressing preventable blindness in India VRSI as a society contributes to public health by taking various initiatives to avoid preventable blindness from different retinal pathologies.

The prime focus of the members of VRSI as a society is to avoid blindness secondary to diabetic retinopathy (DR). India is said to be the diabetes capital of the world and with the increase in the number of diabetics in the country, there is a parallel increase in the number of patients with DR — many of whom are in their working age group, which leads to a great economic burden on the country.

Currently, about 77 million people have diabetes in India, and this number is predicted to drastically increase to 125 million by 2045.

Worryingly, at least three million people are at risk or already have vision loss due to vision-threatening diabetic retinopathy (VTDR) in India.1 With these numbers, it’s clear that intervention is needed to prevent avoidable blindness — and VRSI is actively working to increase public awareness through social media, diabetic retinopathy skill transfer workshops, and webinars, collaborating with online pharmacies and sending out awareness materials and conducting patient awareness workshops. VRSI is also collaborating with other ophthalmic societies, such as the All India Ophthalmic Society (AIOS), to educate general ophthalmologists in diagnosing and treating diabetic retinopathy.

Members of VRSI are also working with IHOPE International to formulate guidelines for diabetic retinopathy diagnosis and management. The Research Society for the Study of Diabetes in India (RSSDI) is the largest organization of all diabetologists and physicians in India with more than 10,000 members.

And VRSI has joined hands with them to formulate the DR screening guidelines for diabetologists.

Furthermore, VRSI is working at various levels including the National Health Scheme to bring in diabetic retinopathy screening as a part of the national health scheme for the

entire population of the country. VRSI also works with various insurance companies to ensure that coverage is given to the majority of diabetics for their intravitreal injections so that they remain compliant with their ongoing treatment and dropout is minimal.

Not only that, VRSI has also conducted DR screening camps to screen soldiers protecting the borders, as well as police personnel and military men, to help maintain their retina health despite being diabetic — thus preventing permanent loss of vision.

Retinopathy of prematurity (ROP) is another retinal pathology where VRSI focuses its resources. This is crucial because India has the highest number of premature births in the world — and further, the country is currently facing an ROP epidemic that has even penetrated its peripheral rural districts.

According to a 2019 paper,2 the incidence of ROP in different regions across India has been reported to range from 38% to 47%.

Advancing medical education and scientific studies Creating opportunities for continued medical education is another primary objective of the VRSI. Members are informed of the latest developments in vitreo-retina through quarterly newsletters, each providing updated scientific information on a selected topic of the retina. Meanwhile, monthly Retina Roundups share new data and trial results to further add to the group’s collective knowledge and establish best practices.

Another valuable resource is the VRSI Study Group, which conducts collaborative research in retina.

The recent paper from the group titled “Incidence of post vitrectomy endophthalmitis in India — A multicentric study by VRSI Study Group” was published in the prestigious journal Eye (London).3 This is a landmark original article highlighting the fact that the reuse of vitreo-retinal instruments as commonly done in the developing countries does not carry a higher risk of endophthalmitis, thereby reducing

the cost of vitreo-retinal surgery.

In developing countries, it is a common practice to re-sterilize single-use instruments — this not only makes surgery more affordable for patients but also reduces the procedure’s environmental impact.

However, these benefits aside, this reuse also raises concerns for postvitrectomy endophthalmitis (PVE), which is reported to be between 0.02% and 0.84%.

Nevertheless, this multicentric study done at 25 sites across India showed no such increase in the risk of endophthalmitis, and it also evaluated the existing sterilization practices of reused instruments in multiple vitreo-retinal centers in India. This study rationalized the use of single-use instruments, thereby making VR surgery more affordable with a lower carbon footprint.

Sharing knowledge to serve others VRSI ensures that the members remain updated with the latest happening in the field of retina by organizing its annual conference held in different parts of the country and attended by more than 700 delegates. Every year, an esteemed faculty both national and international participates to share their knowledge and experiences with all the delegates attending the conference. All the young and

budding vitreo-retinal specialists get an opportunity to showcase their work and learn from the experts.

Various awards are also given during the annual conference, including the Nataraja Pillai award to recognize an international retina specialist for his or her contribution in the field of retina at a global level. Several awards are given to Indian retina specialists for their contributions, such as the Lifetime Achievement Award given to a senior retina specialist who has worked for several decades and helped in bringing up the quality of retina practice in India.

The Young Researcher Award, on the other hand, helps to encourage young researchers’ minds to come up with innovations and new techniques in the field. Not to mention, there are many travel grants given to students, encouraging them for their work and presentations.

Not only does the VRSI annual conference showcase the country’s best talents in the field, but it also provides a platform for knowledge exchange with collaborative research work mixed with fun and socializing.

This year’s meeting will be held from December 1 to 3 in Trivandrum, India.

Registration is currently open.

For more information about VRSI or to register for the conference, visit www.vrsi.in.

References 1. Raman R, Vasconcelos JC, Rajalakshmi R, et al. Prevalence of diabetic retinopathy in India stratified by known and undiagnosed diabetes, urban-rural locations, and socioeconomic indices: results from the SMART India population-based cross-sectional screening study. Lancet Glob Health.

2022;10(12):e1764-e1773.

2. Bowe T, Nyamai L, Ademola-Popoola D, et al. The current state of retinopathy of prematurity in India, Kenya, Mexico, Nigeria, Philippines, Romania, Thailand, and Venezuela. Digit J Ophthalmol.

2019; 25(4): 49-58.

3. Shah PN, Mishra DK, Shanmugam MP, et al. Incidence of post vitrectomy endophthalmitis in India A multicentric study by VRSI study Group. Eye (Lond). 2023 Feb 8. [Online ahead of print]

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Conference Highlights

APAO 2023

Tactics for Better Patient Outcomes

Experts share data-backed updates for screening, diagnosis, and treatments of nAMD and PCV by Brooke Herron At the recently held 38th Asia-Pacific Academy of Ophthalmology Congress (APAO 2023) in Kuala Lumpur, Malaysia, ophthalmologists presented evidence-based diagnosis and treatment recommendations during a session titled, “Neovascular AMD Including Polypoidal Choroidal Vasculopathy.”

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hen it comes to neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), early detection and treatment are key to patient outcomes. As both pose serious threats to vision and quality of life, leading retina specialists placed an emphasis on their screening, diagnosis, and treatment in the final session of APAO 2023.

The impact of timely, targeted nAMD screening There are two important factors to reduce the societal burden of blindness due to macular degeneration, began Prof. Richard Gale. “One is to treat on time and early; and two, identify cases early.”

He shared data from the EDNA study, which found optical coherence tomography (OCT) to be the most accurate and cost-effective in diagnosing conversion to nAMD in the fellow eye.1 “Of course, we don’t know how often we should monitor or screen our patients, but perhaps every three to four months with OCT,” he said. “Healthcare institutions need to fund early treatment and early identification. This leads to better functional outcomes.”

To further reduce costs, Prof. Gale suggested combining diabetic eye disease and AMD screening. “Indeed, East Asia is leading the world in terms of the cost-effectiveness of combining diabetic and AMD screening,” he shared. Noting a paper from Hong Kong, he showed that this strategy is highly cost-effective.2 Timely, targeted screening also results in less fibrosis and smaller lesions, as well as the opportunity to identify geographic atrophy (GA) earlier, he added.

The right drug for the job Antivascular endothelial growth factors (anti-VEGFs) are the go-to injections to treat both nAMD and PCV. However, which drug to use and how often to use it remains a hot topic. Thankfully, for best outcomes in treating PCV, Dr. Won Ki Lee has some straightforward strategies.

Aflibercept monotherapy is very

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PIE MAGAZINE | May/June 2023

more durable drugs that reduce injection frequency (while sustaining BCVA gains over time) are fueling pharmaceutical development in this space. One new drug on the block is faricimab, the first bispecific antibody for intraocular use that independently binds and neutralizes both angiopoietin-2 and VEGF-A. “A lot of our drugs are very superior at drying, but we are struggling to find drugs that allow our patients to be extended longer so they don’t have to come to our clinic as frequently,” said Dr. Kenneth Fong. He was on hand to share the two-year results from the Phase 3 TENAYA and LUCERNE trials, which assessed the efficacy, safety and durability of faricimab versus aflibercept in patients with nAMD.5 The trial authors noted that “the decision to use aflibercept as a comparator aligned well with the findings from the 2020 American Society of Retina Specialists Preferences and Trends survey, which reported that aflibercept was the agent that retina specialists most commonly use as first-line therapy.”

effective in eyes with PCV, shared Dr. Lee. This is based on his involvement in the PLANET study, which showed improvement in visual and/or functional outcomes in more than 85% of participants treated with aflibercept monotherapy, with no signs of leakage from polypoidal lesions in more than 80%.3 He then made an important point when comparing PLANET with EVEREST II (which investigated ranibizumab monotherapy versus combination ranibizumab + PDT for PCV4). “When you look at the data for week 12, about 80% in PLANET achieved a dry macula; on the other hand, only 40% achieved a dry macula in EVEREST II [in the ranibizumab monotherapy arm],” Dr. Lee shared.

Although he admits that he doesn’t understand the fine print (i.e., drug molecules or kinetics) for this difference, he did offer some potential theories. “As a clinician, I could observe that the reduction of choroidal thickness is more frequent and permanent in cases treated with aflibercept. And I think this may contribute to better outcomes as

PCV is suggested to be driven by some choroidal changes,” he said.

“Previously, hyperpermeability of increased choroidal thickness was thought to be a negative factor — but many investigators revealed that aflibercept is also effective in eyes with choroidal vascular hyperpermeability and in pigment epithelial detachment (PED),” he continued. “And I think that drugs that have great effects on the choroid may also have additional therapeutic benefits on the pachychoroid.”

Further, Dr. Lee recommended that physicians take an individualized treatment approach with PCV patients, saying proactive regimens like treat-and-extend (T&E) are desirable. He noted that over 60% of patients can be extended to 12 weeks or beyond.

New drug shows promise in reducing treatment burden Nonadherence and treatment burden are top concerns in patients with nAMD — and as a result,

According to Dr. Fong, patients in the faricimab arm achieved disease control with fewer injections over two years. He explained: “Faricimab achieved a greater reduction mean subfoveal thickness from baseline compared with aflibercept, allowing for rapid treatment interval extension in a majority of patients.”

T&E remains the key treatment regimen for nAMD Looking at a practical, clinical approach to treat and monitor nAMD was Dr. Barkeh Hanim Jumaat, who shared insights from her preferred treatment regimen.

Rather than a reactive protocol like PRN, a more practical, proactive approach is T&E which allows for treatment optimization, said Dr. Jumaat. “And treatment optimization leads to improved visual outcomes and reduced treatment burden.”

With T&E, she explained that injection intervals can be extended two to four weeks between visits, up to a maximum of 12 to 16 weeks — but this interval extension depends on the anti-VEGF agent used. “If

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Conference Highlights

it’s aflibercept, studies have shown that you can go up to 16 weeks; in ranibizumab or bevacizumab, you can do two-weekly increments up to 12 weeks,” said Dr. Jumaat. “The most important point in T&E is that injections should be given at every visit, even if the disease is inactive.”

If a patient is not responding to a particular anti-VEGF, Dr. Jumaat said she would take a conservative approach and consider a switch after five to six monthly injections.

Before switching, she said it’s key to consider whether the treatment was aggressive, if the patient was monitored every q4w, or if the patient could be a delayed responder.

Diagnosing PCV without ICGA Of course, effective treatments and proactive regimens don’t mean much without an accurate diagnosis made with the right diagnostic equipment.

Dr. Voraporn Chaikitmongkol explained that although indocyanine green angiography (ICGA) is the gold standard in diagnosing PCV, 66% of retinal centers in Thailand do not have ICGA. However, the solution to this diagnostic quandary may lie in fundus photography (FP) and OCT. In fact, Dr. Chaikitmongkol has co-

APAO 2023

authored a paper that explores the sensitivity, specificity, and predictive accuracy of potential diagnostic features detected using FP, OCT, and fluorescein angiography (FA) in diagnosing PCV without ICGA.6 The authors came up with four features that can be used to identify PCV — and if two of the four features are identified, a 95% sensitivity and 95% specificity for PCV diagnosis can be achieved. These include: 1) notched or hemorrhagic PED or fibrovascular PED on FP, 2) sharply peaked PED (angle 70-90 degrees) on OCT, 3) PED notch or multilobulated PED on OCT, and 4) hyperreflective ring underneath PED on OCT. Next, she described how OCT features could provide high accuracy in identifying complete or incomplete polypoidal regression following treatment in PCV, highlighting data from another paper7 she co-authored.

In this analysis, OCT characteristics of PED were classified by five prespecified features: A) no PED, B) PED with internal homogeneous reflectivity with predominant BUN (blended retinal pigment epithelium with underlying structure), C) PED with internal homogeneous reflectivity with minimal BUN, D) heterogeneous PED, and E) PED with hyporeflectivity. The results showed that the majority of patients

References 1. Banister K, Cook JA, Scotland G, Azuara-Blanco A, Goulão B, Heimann H, Hernández R, et al. Noninvasive testing for early detection of neovascular macular degeneration in unaffected second eyes of older adults: EDNA diagnostic accuracy study. Health Technol Assess. 2022;26(8):1-142.

2. Chan CKW, Gangwani RA, McGhee SM, Lian JX, Wong DSH. Cost-Effectiveness of Screening for Intermediate Age-Related Macular Degeneration during Diabetic Retinopathy Screening.

Ophthalmology. 2015;122(11):2278-2285.

3. Lee WK, Iida T, Ogura Y, Chen SJ, Wong TY, Mitchell P, Cheung GCM, et al. Efficacy and Safety of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in the PLANET Study: A Randomized Clinical Trial. JAMA Ophthalmol. 2018;136(7):786-793.

4. Lim TH, Lai TYY, Takahashi K, Wong TY, Chen LJ, Ruamviboonsuk P, Tan CS, et al. Comparison of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: The EVEREST II Randomized Clinical Trial. JAMA Ophthalmol. 2020;138(9):935-942.

who achieved complete polypoidal regression had features A (32%) or B (45%); meanwhile, 79% of those who had incomplete polypoidal regression had feature D. “Complete polypoidal regression is another important anatomical outcome for PCV treatment because it’s related to fewer recurrences, longer disease inactivity… and many studies have found that we will need less frequent injections,” said Dr. Chaikitmongkol.

Don’t jump to PCV conclusions While there are certain characteristics associated with PCV — that doesn’t mean it’s always PCV. According to Dr. Gemmy Cheung, some of these masquerading features include blood, multilobulated or peaked PEDs, subretinal fluid and thick choroid, and focal nodular hypofluorescence.

In one example, Dr. Cheung shared patient images (FP, OCT, and ICGA) showing blood — which, at first glance, could be mistaken for PCV. “This is actually a hypertensive patient with a macroaneurysm, which is also one of the common reasons for retinal hemorrhages,” she explained.

“In the past, it was very easy to make this mistake, but when combining with OCT you can see that this is predominantly a preretinal hemorrhage and there is no PED. So this should alert us that while there is a lot of blood, it is not likely to be PCV-related,” said Dr. Cheung, adding that blood from large RPE tears may also be unrelated to PCV. In addition, she recommended reading the Everest study8 on this topic, which describes some of the “famous pseudo-polyps” to look out for.

5. Khanani AM, Guymer RH, Basu K, Boston H, Heier JS, Korobelnik JF, Kotecha A, et al. TENAYA and LUCERNE: Rationale and Design for the Phase 3 Clinical Trials of Faricimab for Neovascular Age-Related Macular Degeneration. Ophthalmol Sci. 2021;1(4):100076.

6. Chaikitmongkol V, Kong J, Khunsongkiet P, Patikulsila D, Sachdeva M, Chavengsaksongkram P, Dejkriengkraikul C, 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.

7. Chaikitmongkol V, Chaovisitsaree T, Patikulsila D, Kunavisarut P, Phasukkijwatana N, Watanachai N, Choovuthayakorn J, et al. Optical Coherence Tomography Features for Identifying Posttreatment Complete Polypoidal Regression in Polypoidal Choroidal Vasculopathy. Asia Pac J Ophthalmol (Phila). 2022;11(5):408-416.

8. Tan CS, Ngo WK, Lim LW, Tan NW, Lim TH; EVEREST Study Group. EVEREST study report 3: diagnostic challenges of polypoidal choroidal vasculopathy. Lessons learnt from screening failures in the EVEREST study. Graefes Arch Clin Exp Ophthalmol. 2016;254(10):1923-1930.

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Editor’s Note The 38th Asia-Pacific Academy of Ophthalmology Congress (APAO 2023) was held on February 23 to 26 in Kuala Lumpur, Malaysia.

Reporting for this story took place during the event.

Industry Update Dry AMD Therapy Shows 24-month Sustained Vision Improvement in LIGHTSITE III Trial

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ata from the US LIGHTSITE III clinical trial are in — and the results are good. Indeed, LumiThera (Poulsbo, Washington, USA) recently announced that early to intermediate dry AMD patients treated with photobiomodulation (PBM) therapy using the Valeda® Light Delivery System demonstrated sustained vision improvement for 24 months.

A prospective, double-masked, randomized, multi-center clinical trial, LIGHTSITE III took place at 10 US retinal centers and enrolled 100 subjects with early to intermediate dry AMD. Patients’ eyes were treated every four months with Valeda; the final treatment occurred at month 21 with the last follow-up visit at month 24.

Investigators’ primary efficacy endpoint was best corrected visual acuity (BCVA).

The investigators noted minimal safety

risks and high compliance with 80% of patients completing the 24-month trial. In total, there were 91 eyes in the PBM-treatment group and 54 in the sham-treatment group. At 24 months, the BCVA improvement from baseline in the PBM group was significantly greater than the sham group, 5.9 vs 1.0 letters (p = 0.0015). Further, approximately 58% of the PBM-treated eyes had >5 letter gain, with a mean increase of 8.5 + 0.5 letters. Eyes in the PBM group demonstrated this improvement at month 21 (after the last treatment); this was sustained throughout the trial’s conclusion at month 24.

During the trial, patients also underwent detailed retinal morphology analysis using OCT. Dr. Glenn Jaffe, a vitreoretinal surgeon and professor of ophthalmology at Duke University Eye Center, explained that fewer eyes progressed to new geographic atrophy.

The 24-month OCT data indicated

that five of 88 eyes (5.7%) in the PBM group progressed to new GA, whereas 11 of 51 eyes (21.6%) in the sham arm developed new GA. “PBM treatment showed a statistically significant (p = 0.003) slowing of disease progression in patients with early to intermediate dry AMD,” stated Dr. Jaffe.

Not only is PBM treatment a significant advancement in saving sight for AMD patients, but it’s also non-invasive, explained Dr. Diana V. Do and Dr. Quan Dong Nguyen. Both Dr. Do and Dr. Nguyen are members of the Retina Division at the Byers Eye Institute at Stanford University, one of the clinical sites for LIGHTSITE III. “We are in urgent need of therapy for our patients with dry AMD, especially if the treatment is non-invasive such as the Valeda Light Delivery System,” they said.

Industry Update Demand for Bionic Eye Set to Hit US$1B Market Value by 2033

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ionic eyes (or visual prostheses) create a sense of vision and light perception for those with advanced vision loss — and the ability to restore any semblance of sight is a gift for those affected by sight-threatening eye disease.

The need for these advanced medical devices is only going up: A recent market study by Fact.MR predicts the demand for bionic eye technology to rise at a CAGR of 13%, increasing the global market value from US$297.1 million in 2023 to US$1 billion in 2033.

The recently released report detailed some key factors driving this rapid growth, including recent innovations

and the higher prevalence of eye disease leading to vision loss.

According to a Fact.MR analyst, rapidly increasing older populations who are more prone to eye disease, along with the rising prevalence of diabetic retinopathy, are contributing to the demand for bionic eye technologies.

Further, innovation in the technology itself has led to an uptick in uptake — today’s bionic eyes provide better vision, and they’re more comfortable to use. One such example is the Argus II Retinal Prosthesis System from Second Sight Medical Products, Inc., which allows patients to perceive light patterns and images via a wireless

implantable device that provides electrical stimulation to the retina.

Bionic eye solutions are also more affordable, thanks to dedicated investment into research and development from key industry players.

In addition, the researchers found that bionic eye tech is booming in three regions in particular. In the United States, well-established healthcare facilities and key market players are driving sales. Meanwhile, in Germany, the older population is the primary factor for increased demand. In addition, the market is also expanding in Australia, thanks to its advanced medical technologies and researchers.

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