PIE Issue 21: The ebook version (The Sustainability Issue)

Dr. Alay S. Banker is the director of Banker’s Retina Clinic and Laser Centre in Ahmedabad, India and his practice has served the city since 2007. He started off his career as a clinical instructor and fellow at the Department of Diseases of Retina and Vitreous, Uvea and Inflammation of Eye at University of California, San Diego, USA. He was the first Indian to receive the “International Scholar Award” from AAO in 2010 and also the youngest Indian to receive the Achievement Award by the AAO in 2006. His contributions toward his medical peers and community services have also earned him the Senior Achievement Award from AAO (2013) and the Dr. Piyush Patel Award for Service to Society and Mankind from Ahmedabad Medical Association (2013). He is the senior founding editor of the Retina Image Bank (ASRS 2012), has presented at more than 250 international and national conferences with over 40 papers published in peer-reviewed medical journals, and has published five book chapters in international book publications.

alay.banker@gmail.com

Prof. Gemmy Cheung is currently a professor at Duke-NUS Medical School, National University of Singapore, and head of the Medical Retina Department at Singapore National Eye Center (SNEC). Her research focuses on retinal diseases, including age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV) and myopic macular degeneration, as well as risk factors for these conditions that may be unique to Asian populations. Prof. Cheung has more than 200 peer-reviewed publications and serves on the editorial boards of several journals, including the American Journal of Ophthalmology, Retina and Eye.

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

Dr. Hudson Nakamura is an ophthalmologist specializing in the retina and vitreous. He completed his medical degree from School of Medicine at the Federal University of Goiás, UFG and residency from the Base Hospital of the Federal District, Brasília, DF. Presently, Dr. Nakamura is a member of the AAO, Brazilian Council of Ophthalmology, Canadian Society of Ophthalmology and ARVO. He currently works as a professor in the Department of Retina and Vitreous Course of Medical Residency in Ophthalmology at the Bank of Goias Eye Foundation. Dr. Nakamura holds a vitreoretinal disease fellowship from the University of Toronto Canada and the Brazilian Center for Eye Surgery.

hudson.nakamura@gmail.com

Dr. Kenneth Fong is recognized as an ophthalmologist in the United Kingdom, Australia and Malaysia. He graduated with a medical degree from the University of Cambridge in 1998 and trained to be an eye surgeon in London. Dr. Fong then spent two more years training in the U.K. and at the Royal Perth Hospital in Australia to subspecialize in retina. After 18 years of working in the U.K. and Australia, he returned to Malaysia in 2009 to serve as associate professor, consultant ophthalmologist and retinal surgeon at the University of Malaya in Kuala Lumpur. He is currently the managing director of OasisEye Specialists in Kuala Lumpur. Dr. Fong is the president of the Malaysian Society of Ophthalmology and serves as a council member for the APVRS.

kcsfong@gmail.com

Dr. Alay S. Banker

Dr. Kenneth Fong

Prof. Gemmy Cheung

Dr. Hudson Nakamura

Prof. Mark Gillies presently holds a number of positions including: director of research and director of the Macula Research Group for the Save Sight Institute; foundation fellow for the Sydney Medical School; professor in the Department of Clinical Ophthalmology at the University of Sydney; head of the Medical Retina Unit at the Sydney Eye Hospital; deputy chair for the Ophthalmic Research Institute of Australia; and director of Eye Associates in Sydney. Prof. Gillies has served as a principal investigator or associate investigator in more than 70 clinical trials, and his research regarding macular degeneration and drug safety and efficacy has been published in 188 journals. He has also received a number of grants to study treatments for age-related macular degeneration, retinal disease and Muller cell dysfunction – among other treatments and studies. Prof. Gillies is a dedicated and multi-awarded researcher.

mark.gillies@sydney.edu.au

Dr. Saad Waheeb is an associate professor of ophthalmology and a senior academic consultant. He is the ophthalmologist-in-chief at King Faisal Specialist Hospital & Research Centre in Riyadh, Saudi Arabia. He is also the CEO and founder of First Lens Eye Center. Dr. Waheeb’s specialty is on the diseases and surgery of the retina and vitreous with special interest in diabetic retinopathy and retinal vascular disorders. He has published in the field of retina and has been an invited speaker both nationally and internationally. He is a founding member of the Saudi Retina Society. He completed his residency and retinal fellowship in vitreoretinal diseases and surgery at the University of Toronto, Canada.

saadwaheeb@hotmail.com

SOCIETY FRIENDS

Prof. Mark Gillies

Dr. Saad Waheeb

Asia-Pacific Vitreo-retina Society

ASEAN Ophthalmology Society

Arunodaya Charitable Trust (ACT)

Asia-Pacific Academy of Ophthalmology

He Eye Specialist Hospital Ophthalmology Innovation Summit

Retinawesome Retina & Vitreous International

Orbis Singapore Subthreshold Ophthalmic Laser Society

Vitreo-Retinal Society - India

Young Ophthalmologists Society of India ( YOSI )

Russian Ophthalmology Society (ROS)

It’s Time to Go Green

Dear Readers,

limate change is a threat facing every person living today — and even more so for generations yet to come. It’s indisputable that rising temperatures impact weather patterns around the world, and these extreme events will have consequences in health care, including ophthalmology.

Indeed, a 2020 editorial* penned by El Hamichi et al., stated that “the intriguing chain reaction of global warming in ocular health is ominous.” Maybe it’s just me, but the word “ominous” gives me the heebie-jeebies — and it’s not a term I’d particularly like to associate with the global future of ocular health.

Climate change is happening, whether we like it (or believe it) or not — and while much environmental damage has already been done, there is still time to make corrections to the way we (literally) operate to reduce ophthalmology’s contribution to carbon emissions.

It’s no secret that the health care sector is a MAJOR contributor to waste and carbon emissions. And it’s not necessarily our fault — there are federal regulations we must follow, or be liable for litigation (at least in the grand ol’ U.S. of A.). And of course, much of the generated waste is a result of the overarching goal of keeping patients safe from infection. (However, in some cases, it could be argued that these regulations are more about safety from litigation than actual patient protection … but I digress.)

CSo, what — as the ophthalmic community — can we do? The first step is recognizing the problem and increasing awareness. Will putting a recycling bin in the break room save the planet? Probably not. But what if every practice, clinic and hospital did so? Sure, we’d recycle more — but importantly, we’d increase awareness with the goal of affecting future behavior.

Sustainability is nothing new in eye care — we’re always seeking ways to make medical practice more efficient to conserve resources. But now, we should also focus on ways to reduce waste. And while vitreoretinal specialists might not produce as much waste as their cataract-removing colleagues, posterior segment practice still owns its own carbon footprint.

Look at anti-VEGF injections, for instance. Often prescribed monthly, this sight-preserving treatment owns its share of carbon emissions — and not for the reason you may think: It’s the result of routine patient travel to the clinic. Unused items in disposable kits are an absolute waste, too — but this can be combated as well via the creation of surgeon-tailored packs. Gases used in ophthalmic surgery are another main driver of carbon emissions in vitreoretinal practice — but the use of these volatile elements could be replaced with air tamponade. These are but a few targets we should focus on for a more sustainable practice.

I encourage you to read this issue’s cover story, which looks into what has been done — and what could be done still — to reduce carbon emissions in vitreoretina. Even small changes can make a big impact, overall.

And until next time, stay “green” ophthalmic friends!

Cheers, Brooke Herron Editor, PIE, CAKE & COOKIE magazines

* El Hamichi S, Gold A, Murray RG, Kon Graversen V. Pandemics, climate change, and the eye. Graefes Arch Clin Exp Ophthalmol. 2020; 258(12): 2597–2601.

Autophagy’s Key Role in Retinal Disease Treatment

Autophagy could protect retina and eye cells from disease, underscoring its potential role in the treatment of ocular pathologies, according to recent findings. In a paper titled New Insights into the Role of Autophagy in Retinal and Eye Diseases* by Villarejo-Zori et al., the authors concluded that the studies they reviewed highlight “the significant role of autophagy in sustaining the function of both the neural retina and the RPE” and its involvement in some of the most prevalent diseases of these structures, from age-related macular degeneration (AMD) to glaucoma.

In the paper, the authors reviewed the roles of both canonical and noncanonical autophagy in normal retinal

by Hazlin Hassan

function. The authors also discussed the most recent studies investigating the participation of autophagy in eye disease such as AMD, glaucoma and diabetic retinopathy, as well as its role in protecting photoreceptors in several forms of retinal degeneration.

The paper noted that the retina is a light-sensitive tissue located in the back of the eye that detects and processes visual images. It added that vision is a highly demanding process, making the eye one of the most metabolically-active tissues in the body and photoreceptors display glycolytic metabolism, even in the presence of oxygen.

“The retina and eye are also exposed to other stressors that can impair their

function, including genetic mutations and age-associated changes. Autophagy, among other pathways, is therefore a key process for the preservation of retinal homeostasis,” the investigators said.

The link between autophagy and eye disease

Autophagy proteins play key roles in the retina including quality control functions, elimination of toxic aggregates, facilitation of photoreceptor outer segment (POS) degradation and visual pigment recycling to sustain photoreceptor function.

One of the findings of the paper is that autophagy plays an important role in

glaucoma by regulating both intraocular pressure (IOP) and the response to retinal ganglion cell (RGC) damage caused by the disease.

One of the leading causes of blindness worldwide, studies estimate that at least 111.8 million people will be diagnosed with glaucoma by the year 2040.

The two main risk factors for glaucoma are increased intraocular pressure (IOP) and aging. However, the pathophysiology of glaucoma still remains unclear. Genetic studies indicate a link between glaucoma and autophagy-related genes.

Levels of autophagy in the brain and retina decline with age, which is thought to contribute to the pathogenesis of various age-related degenerative diseases, including glaucoma.

Autophagy plays an important role in glaucoma by regulating both IOP and the response to RGC damage caused in this disease.

A better understanding of the role of autophagy within the different RGC compartments and the relevance of age-related changes in autophagy is necessary to fully realize the potential of autophagy as a therapeutic target in glaucoma.

In RGCs, autophagy has been linked to axonal homeostasis and has a protective function, possibly by minimizing ROS levels and sustaining mitochondrial function. In certain conditions, blockade of autophagy in a specific subtype of RGCs has been shown to improve the pathogenic phenotype and reduce vision loss.

Autophagy is also important in the retinal pigment epithelium (RPE) to preserve degradative capacity, provide metabolic support and ensure quality control. “Thus, it is clear from the literature that alterations in autophagy and lysosomal pathways are implicated in many, if not all, diseases of the eye. Moreover, the decline in lysosomal activity associated with age exacerbates alterations in autophagy, potentially aggravating related conditions,” said the paper.

However, the paper cautions that overactivation of autophagy in a cell type-dependent manner may have detrimental consequences in the context of light-induced photoreceptor damage. Future studies will help further the understanding of the potential of therapeutic strategies that target autophagy and the lysosomal pathway in diseases of the retina and eye, it concluded.

More research is needed

According to the World Health Organization, blindness is one of the most debilitating disabilities, resulting in significant impairment of social activity.

Diseases such as glaucoma, diabetic retinopathy and AMD collectively accounted for more than 19 million cases of moderate or severe vision impairment in adults aged 50 years and older in the year 2020. However, the molecular bases of these diseases are not completely understood and the lack of good mouse models hampers the

development of effective treatments.

As such, identifying the causes of these diseases, as well as understanding how the retina responds to stress, is essential to facilitate the development of novel, effective treatments for eye diseases.

Autophagy, among other pathways, is a key process for the preservation of retinal homeostasis. Because autophagy plays an important role in removing damaged organelles and proteins in these different cell compartments, it is important to understand how this process is specifically regulated in each compartment.

These challenges, and the manner in which they are resolved in different cell types, can affect the cell's response to stress. More research is needed to understand how the autophagy process is regulated in different cell types of the eye.

There is also an urgent need for disease models that better reproduce the alterations observed in human patients with retinal and eye diseases. In conclusion, more research is needed in order to boost the development of autophagy-targeting therapies to treat retinal diseases.

* Villarejo-Zori B, Jimenez-Loygorri JI, ZapataMuñoz J, et al. New insights into the role of autophagy in retinal and eye diseases. Mol Aspects Med. 2021;82:101038.

Researchers are unraveling autophagy’s role in retinal disease

The Rise of Anti-VEGF Biosimilars and Biobetters

by Tan Sher Lynn

As the patents for anti-VEGF agents expire, biosimilars and biobetters are rising in the market…

Over the years, anti-vascular endothelial growth factor (anti-VEGF) therapies, such as bevacizumab, ranibizumab and aflibercept, have significantly improved visual outcomes in patients with neovascular age-related macular degeneration (nAMD) by halting the abnormal growth of blood vessels that lead to subretinal bleeding. These drugs

also treat diabetic macular edema and retinal vein occlusion.

Nevertheless, the U.S. patents for ranibizumab and aflibercept expired in 2020, and their European patents will expire in 2022 and 2025, respectively. With this, authors of the recently published paper entitled Future of anti-VEGF: Biosimilars and Biobetters* predicted that biosimilars and biobetters will become increasingly important and prominent in the market, thanks to their affordability and availability.

Recent developments in biosimilars

The World Health Organization (WHO) defined biosimilars as biotechnological products that are comparable with an already approved reference product in quality, nonclinical, and clinical evaluation. A biosimilar molecule should resemble the innovator biologic in terms of pharmacokinetics, pharmacodynamics, safety and efficacy.

While generics can be easily synthesized

by matching the formula, biosimilars require living cells during the manufacturing process. Manufacturers of biosimilars must proceed with partial, incomplete information and reverse engineer the original biologic. Hence, the investment and the research required to manufacture biosimilars are considerably higher than developing generic drugs.

For the time being, approval of biosimilars does not follow any fixed guidelines, and is up to the discretion

of each country. Nevertheless, some basic principles exist, including analysis to establish biosimilarity, toxicity assessment through animal studies, and a clinical study to understand the biosimilar’s safety, efficacy and immunogenicity.

Razumab® (Intas Pharmaceuticals Ltd., Ahmedabad, India) is the first biosimilar to ranibizumab. It was approved in India in 2015 and has been in clinical use since then. Today, a total of 10 manufacturers are working on a ranibizumab biosimilar, including R-TPR-024/Ranizurel (Reliance Life Sciences, India), which was approved by Indian regulators in 2020; FYB201 (Formycon and Bioeq, Germany), for which satisfactory phase 3 clinical results have been reported; and those in phase 3 clinical trials: Xlucane (Xbrane Biopharma, Sweden), SJP-0133/GBS007 (Senju Pharmaceutical, Japan), LUBT010 (Lupin, India), and CKD-701 (Chong Kun Dang, Republic of Korea).

Also, various aflibercept biosimilars are in the pipeline as well, with the majority of them in phase 3 clinical trial, such as ABP-983 (Amgen, USA), FYB203 (Formycon AG/Bioeq, Germany), SB-15 (Samsung Bioepis Co. Ltd, South Korea), SOK583A19 (Sandoz, Switzerland), and CT-P42 (Celltrion, South Korea). Meanwhile, MYL-1701P (Momenta Pharmaceuticals and Mylan NV, USA) has completed its phase 3 clinical trial.

As for bevacizumab biosimilars, many of them are already approved and on global markets, such as Zirabev (Pfizer, USA), ABP215 (Amgen, USA), Cizumab (Hetero, India), Bevacirel (Reliance Life Sciences, India) and Abevmy (Mylan Pharmaceuticals, South Africa).

What about biobetters?

While biosimilars have the same amino acid sequence and are highly similar to reference products, biobetters may be modified chemically and have a different amino acid sequence or purification process, resulting in a better drug with increased shelf life and pharmacological effects.

Like biosimilars, the biobetter market has a vast potential to grow

exponentially. A disadvantage would be the high cost for research and development, which could be 10 times higher than manufacturing a biosimilar. On the positive side, a biobetter has a high chance of reaching the production stage, and a shorter research and development duration, since they do not need to wait for patents and market exclusivity to expire, therefore bringing in faster financial returns to companies who produce them.

A couple of recent biobetters developments include a port-based delivery system for ranibizumab, which is being developed by Genentech, to improve drug delivery, efficacy and reduce treatment cost. South Korea’s Ildong Pharmaceutical is also working on a biobetter based on ranibizumab to improve efficacy and reduce drug resistance in AMD patients receiving ranibizumab.

Over the next decade, the authors predicted that many potential biosimilars will be entering the market, as there’s a huge need for ophthalmic biosimilar products especially in developing countries, due to the lack of compounding pharmacies in these countries. They stressed that “pharmacovigilance, quality control and monitoring are particularly important, along with immunogenicity testing assay before market approval to prevent any batch-specific clusters of adverse drug reactions.”

* Kapur M, Nirula S, Naik MP. Future of anti-VEGF: biosimilars and biobetters. Int J Retina Vitreous. 2022;8(1):2.

Rethinking Glaucoma Pathology

Recent Study Offers New Insights on How Retinal Ganglion Cells Communicate

by Joanna Lee

Anew study has uncovered the finer mechanisms behind damaged pericyte cells and the nanotube tunnels that provide communicative connections between them in glaucomatous eyes. This has raised hope toward developing potential therapeutics aimed specifically at addressing these microvascular deficits.

University of Montreal Hospital Research Centre’s Professor Adriana Di Polo led the study. Co-authored by lead postdoctoral research fellows

Luis Alarcon-Martinez and Yukihiro Shiga, together they discovered how defective inter-pericyte tunneling nanotubes (IP-TNTs) lead to disruptions in neurovascular coupling as seen in glaucomatous eyes.1

Glaucoma is characterized by reduced blood flow and poor neurovascular connectivity. It has been long theorized

that this lack of blood flow contributes to the degeneration of retinal ganglion cells (RGCs),2 the neurons that connect the retina to the brain, and as a result, enable the development of glaucoma.

However, the understanding of the finer workings of these microvascular deficits which contribute to vision loss at the molecular level has yet to be attained. Until now…

Gaining more understanding

Pericyte cells regulate the flow of blood running through each capillary via a mechanism of contraction and relaxation wrapping around the capillary. This constriction and release of the capillaries is very much dependent on the level of calcium present in the pericytes.

Carrying signals of communication between these pericyte cells are the IPTNTs, as the research team discovered in their recent study.3 The discovery of these nano-tubular processes has given researchers a better understanding of how blood is dispersed within retinal capillary networks while responding to neural activity.

Further, the researchers sought to understand the roles played by pericytes and IP-TNTs in the neurovascular coupling abnormalities found in glaucoma. The team used live microscopy imaging of mice retinas in a preclinical ocular hypertensive model (OHT) to recreate the conditions of open angle glaucoma (OAG), the more common form of the disease. OAG is characterized by a gradual increase in intraocular pressure (IOP) and the accumulation of magnetic microbeads at the trabecular meshwork.

The results indicated several important key findings that shed light on the finer mechanisms behind the neurovascular dysfunction in glaucoma.

First, it demonstrated that higher IOP within pericytes negatively affected the pathology of microvascular damage in glaucoma, as they found capillary diameter reductions, decreased blood flow and defective neurovascular coupling.

Second, their findings suggest that in glaucoma, IP-TNTs' structural and functional integrity, as well as their ability to serve as a conduit of signals between connected pericytes, were disrupted.

The role of calcium equilibrium

Knowing that calcium plays a role in regulating the contraction and release mechanism of the pericyte cells,4 the researchers tested this and further found that an excess of calcium in the IP-TNT causes disruptions to normal microvascular flow. In essence, lowering calcium levels can restore IP-TNT balance, reinstating capillary functioning, blood flow and neurovascular coupling.

in pericytes led to the repair of cell functions, particularly its neural response to light, and this subsequently improved the survival of RGCs.

The findings challenge the conventional views of glaucoma pathology: That neuronal loss is more prominent than what happens at the vascular level. This deeper insight into vascular pathology at the early stages of glaucoma has caused the researchers to ponder if pericyte or capillary defects could cause neuronal dysfunction. The answer seemed to be a “yes.”

Another discovery from this study was that until recently, smooth muscle cells on arterioles were thought to be the only regulator of cerebral blood flow. Most research on vascular dysregulation in glaucoma patients have focused on abnormalities at the level of arterioles.5, 6

The researchers suggested that the continuous damage to the neurovascular system caused at the pericyte level will impair the function of the RGCs in the long run.

These findings also point to the idea that the reduction in pericyte-induced blood flow, which obstructs oxygen and food supply to energetically demanding RGCs,7 causes dysfunction at the neuronal level — thus, making these neurons more vulnerable to the stresses related to IOP.

Overall, the significance of the discovery is in the continued survival of the RGCs when surplus calcium, which causes damage to the pericyte, is readjusted to a state of homeostasis.

The researchers earmarked pericytes as a target for potential therapeutics for glaucoma, perhaps offering a glimmer of hope at the end of the nanotube’s “tunnel” for the 80 million glaucoma patients worldwide.8 Furthermore, other neurodegenerative diseases involving vascular aspects could be similarly targeted as well.

References:

1. Alarcon-Martinez L, Shiga Y, VillafrancaBaughman D, et al. Pericyte dysfunction and loss of interpericyte tunneling nanotubes promote neurovascular deficits in glaucoma. Proc Natl Acad Sci U S A. 2022;119(7):e2110329119.

2. Flammer J, Haefliger IO, Orgül S, Resink T. Vascular dysregulation: a principal risk factor for glaucomatous damage?. J Glaucoma. 1999;8(3):212-219.

3. Alarcon-Martinez L, Villafranca-Baughman D, Quintero H, et al. Interpericyte tunnelling nanotubes regulate neurovascular coupling. Nature. 2020;585:91-95.

4. Burdyga T, Borysova L. Ca2+ signalling in pericytes. Adv Exp Med Biol. 2018;1109:95–109.

5. Wareham LK, Calkins DJ. The neurovascular unit in glaucomatous neurodegeneration. Front Cell Dev Biol. 2020;8:452.

6. Newman A, Andrew N, Casson R. Review of the association between retinal microvascular characteristics and eye disease. Clin Exp Ophthalmol. 2018;46:531–552.

The results also demonstrated that restoring the equilibrium of calcium Editor’s

7. Ito YA, Di Polo A. Mitochondrial dynamics, transport, and quality control: A bottleneck for retinal ganglion cell viability in optic neuropathies. Mitochondrion. 2017;36:186–192.

8. Tham Y-C, Li X, Wong TY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and metaanalysis. Ophthalmology. 2014;121:2081–2090.

It’s been just over 50 years since Dr. Robert Machemer changed the world of ophthalmology by performing the first vitrectomy surgeries. Since that time, the procedure has become more and more commonplace in the operating room, and has done a world of good in terms of improving eyesight and preventing vision loss.

Surgical procedures for diabetic retinopathy, retinal detachment and eye trauma all commonly involve replacing the vitreous in some form. While many doctors steer away from it, the procedure is even performed to treat far less threatening conditions, such as floaters, for which vitrectomy is becoming a more accepted solution.1

Yet as long as there have been vitrectomies, there has been a search for a better substitute for the vitreous. As the vitreous is not actively regenerated or replenished by the eye, a replacement must be introduced into the eye.

In Pursuit of a Biomimetic Replacement for Vitreous

Could Hydrogels be the Answer?

by Nick Eustice

Numerous substances have been tried, and many are still in use today. But each has its ups and downs as a substitute for the natural fluid within the eye, and there is still considerable discussion as to which balance of advantages and drawbacks is the best choice in a given set of circumstances.

Previous substitutes for vitreous

For short-term applications, air or other colorless inert gasses are frequently used to replace the vitreous. This method is especially common during vitreoretinal surgery, where gasses with comparatively low refractive index and viscosity make for easier operating conditions while maintaining an effective tamponade to ensure appropriate retinal position.

These materials are not necessarily appropriate replacements in the longer

term, however, as their presence in the body can lead to complications related to atmospheric sensitivity in the patient.

Saline solutions are also commonly used, with chemical characteristics quite similar to the body’s own aqueous humor in terms of transparency, refractive index and density.2 This presents the opposite problem to that of using gas, in that the low pressure of the saline solution does not provide effective tamponade properties for keeping the shape and position of the retina. As a result, the two are often used in conjunction with one another.

In recent years, numerous alternative materials have been used as replacements for the vitreous as well. Perfluorocarbon liquids (PFCls) and semifluorinated alkanes (SFAs) have been developed that very closely mimic the body’s own fluid. Over time, however, these both have shown repeated instances of retinal toxicity and

intraocular inflammatory reactions when left in the eye after surgery.

Silicone oil has become increasingly popular in recent years, as it has generally shown to be a less toxic alternative that adapts well to the eye’s shape and biological composition. This is especially significant as it can be left in the eye for a longer period of time with few or no negative side effects. In the long-term, however, even silicone oil produces toxic effects after enough time. Silicone oil has also produced instances of unacceptable emulsification in some patients, requiring surgical removal.

Polymeric hydrogels: The new frontier

Over the past 10 years, polymeric hydrogels have become more and more common in various fields, particularly in medicine. Hydrogels are crosslinked 3D networks of hydrophilic polymer chains.3 And because they are hydrophilic in structure, they are capable of holding large amounts of water — it is this property which, when they are introduced into the body, make polymeric hydrogels especially effective in terms of integrating with the body’s own natural tissues.

Hydrogels have been used in various medical applications as a result of their adaptability to the body. They are used in engineering bone tissue, as drug delivery systems, and as medical electrodes. Modern contact lenses are all made of forms of hydrogels. And

recently, they have been posited as the most viable replacement material for the vitreous.

A recent article published by Schulz et al. suggests that polymeric hydrogels will constitute the next frontier in novel vitreous substitutes, and indeed in vitreoretinal surgery, in general.4 In this article, they suggest that hydrogels have significant advantages over all other currently available replacements for vitreous. Among these advantages, is the higher degree of responsiveness to conditions within the eye such as pressure, as well as the unique chemical makeup of the eye.

The idea of hydrogels as a more biomimetic replacement for vitreous than those currently in use is not a new one. Writing in the International Journal of Ophthalmology in 2015, Gao et al. noted that hydrogels hold the best potential as replacements for the body’s own vitreous due to their flexibility, transparency and biocompatibility.5 This, they note, is especially the case in long-term applications, as no acceptable alternative for the truly long term has yet been discovered.

This long-term potential is due to the biodegradable and highly mimetic nature of hydrogels. Unlike silicone oil — the only other realistic option for long-term application — hydrogels interact with the body’s internal chemistry, rather than providing a neutral, minimally invasive material. Over time, hydrogels have the potential to assimilate with the eye’s delicate balance, rather than

eventually being rejected as a foreign substance.

In 2015, no hydrogels had been developed that had reached the clinical trial stage. While this is still the case, many preclinical trials have been conducted, and Schulz et al. advocate for moving forward with exploring these more versatile materials in clinical trials. They note that numerous such hydrogelbased vitreous substitutes have shown highly encouraging results in preclinical trials, and could be of tremendous benefit to patients for whom a long-term solution is needed.

The great leaps forward in vitreoretinal surgery that have been made in the past 50 years have brought tremendous relief to countless patients, and it is encouraging to see that more and more breakthroughs come about every day. It is possible that polymeric hydrogels could soon provide a viable and widelyused alternative to vitreous in surgical patients.

References:

1. Katsanos A, Tsaldari N, Gorgoli K, et al. Safety and Efficacy of YAG Laser Vitreolysis for the Treatment of Vitreous Floaters: An Overview. Adv Ther. 2020; 37(4): 1319–1327.

2. Baino F. Towards an ideal biomaterial for vitreous replacement: historical overview and future trends. Acta Biomaterialia. 2011;7(3):921–935.

3. Chai Q, Jiao Y, Yu X. Hydrogels for Biomedical Applications: Their Characteristics and the Mechanisms behind Them. Gels. 2017; 3(1): 6.

4. Schulz A, Januschowski K, Szurman P. Novel vitreous substitutes: the next frontier in vitreoretinal surgery. Curr Opin Ophthalmol. 2021;32(3):288-293.

5. Gao Q-Y. Fu Y, Hui Y-N. Vitreous substitutes: challenges and directions. Int J Ophthalmol. 2015; 8(3): 437–440.

Editor’s Note:

Study Highlights

Robotic Developments in Vitreoretinal Surgery

by Andrew Sweeney

Ah, robotics. They are a staple of our imaginations, with visions of the future often predicated on either utopia (where labor is made unnecessary by advanced AI technology) or dystopia (where the Terminators take over and mankind is reduced to little more than cell batteries). But while these sciencefiction conjurings are interesting — they’re hardly grounded in reality — and of very little use to ophthalmology. In reality however, robotics offer remarkable transformative value in ophthalmology, especially in vitreoretinal surgery.

Vitreoretinal surgery has experienced remarkable development in the last few decades to the benefit

of millions of patients, whether suffering from macular hole, excessive floaters or diabetic retinopathy. Particularly game-changing in this field was the development of the closed pars plana vitrectomy by Robert Machemar, which eliminates the need for keratoplasty and operates with a closed system with controllable intraocular pressure.1 Since its invention in the 1970s, this contribution has remained a gold standard. But now, thanks to advances in robotics and optical coherence tomography (OCT), new innovations have appeared with great promise.

New technology for steadier hands

A Review of Robotic and OCT-Aided Systems for Vitreoretinal Surgery, was drawn up by three researchers from Vanderbilt University (Nashville, Tennessee, USA). The paper highlights leading developments in the application of robotics technology and OCT in vitreoretinal surgery. Specifically, the paper examines new techniques that can overcome barriers of perception, tremor and dexterity that are nearing its feasibility for clinical use.

According to the Vanderbilt researchers, there are four technologies that are particularly promising: handheld instruments with intrinsic robotic assistance, teleoperated robotic systems, hand-on-hand robotic systems, and magnetic guidance robots. Pointing out that vitreoretinal procedures often depend on the safe manipulation of the delicate anatomy of the retina, these new techniques need to offer the user as smooth a procedure as possible with minimal strain or stress.2

Beginning with handheld systems, the researchers found that a number of promising tools have been developed, especially the Micron, which was designed to sense a surgeon’s tremor and distinguish those movements

from intentional motion.3 The Micron device achieves this by leveraging the effects of constructive and destructive interaction of wave signals to filter the user’s tremor from the tooltip. After analyzing the tool’s application, they found that it had a success rate of 63% in experimental vessel cannulation,2 highlighting its efficacy thanks to sensors at the tool's tip that isolate retinal forces from the sclerotomy interaction forces, ensuring damaging forces on the retina are not applied.

Dutch robotics and huge magnets

The section covering teleoperated robotic systems was the most comprehensive section of the study and is well worth a paper in its own right. The study highlights several interesting developments, in particular, the Preceyes Surgical Robotic System (Preceyes, Eindhoven, the Netherlands) stood out as it has motion control that the surgeon uses to command surgical tooltip position. The minimized interaction forces between the surgical tool and sclerotomy mitigates scleral trauma and the device also includes external OCT imaging to establish tool tip boundaries.2

The study draws attention to the benefits of hand-on-hand robotic systems as they can enable microsurgeries that are impossible with traditional surgical tools, though this does require a degree of skill. The Steady-Hand, a cooperative robotic system, is singled out for praise

as it allows for smooth, natural motion profiles that a surgeon would typically use during retinal procedures without extraneous tool movements.4 It also includes combined inputs from OCT imaging and minimizes resistance to limit membrane tearing.2

Finally, the last section to be covered by the study looks at magnetic guidance robots, a relative novelty that emerged over the last decade, which utilizes an extraocular magnetic field to control robotic microcapsules within the eye for procedures like retinal vein cannulation. According to the Vanderbilt researchers, this technology’s advantage is that it can achieve high levels of intraocular dexterity and maneuverability without physical attachment to the extraocular space. However, this includes a drawback, namely the expense of complex magnetic field generators that need to be placed around the patient’s head.2

Editor’s Note: A version of this article was first published on piemagazine.org.

References:

1. The History of Vitrectomy: Innovation and Evolution. Retina Today. Available at https:// retinatoday.com/articles/2008-sept/0908_05-php. Accessed on February 2, 2022.

2. Ahronovich EZ, Simaan N, Joos KM. A Review of Robotic and OCT-Aided Systems for Vitreoretinal Surgery. Adv Ther. 2021;38(5):2114-2129.

3. Becker BC, Voros S, Lobes LA, et al. Retinal Vessel Cannulation with an Image-Guided Handheld Robot. Conf Proc IEEE Eng Med Biol Soc. 2010; 2010: 5420–5423.

4. Taylor R, Jensen P, Whitcomb L, et al. A Steady-Hand Robotic System for Microsurgical Augmentation. Int J Robot Res. 1999;18(12):1201–1210.

Lowering the carbon footprint of vitreoretinal practice

by Brooke Herron

In 2019, The Lancet published a report on health and climate change.1 Within the report was this statement: “The life of every child born today will be profoundly affected by climate change. Without accelerated intervention, this new era will come to define the health of people at every stage of their lives.”

Take a moment to let that sink in.

That statement illustrates the undeniable fact that while the world faces numerous threats and challenges, one of (if not the most) critical is that of climate change. Eye health will also be impacted, directly or indirectly, from the extreme weather conditions brought on by the earth’s rising temperature. These include an increased incidence of trachoma infections, vitamin A deficiency eye conditions, cataracts,

allergic eye diseases, glaucoma and agerelated macular degeneration (AMD).2

Basically, an unhealthy planet leads to an unhealthy everything else — including eyeballs. So, if we want to continue today’s activities tomorrow, we need to act now and implement more sustainable practices.

Ophthalmology and the climate crisis

It’s no secret that the medical field, in general, produces a large amount of waste: It’s a major contributor to carbon emissions, with waste production and transport systems being among the highest contributing factors.2

And although ophthalmology might be

a smaller specialty compared to say, cardiology, it contributes significantly to healthcare’s carbon footprint. The main culprits driving ophthalmology’s contributions to the climate crisis are high surgical volumes (hello, cataract surgery), single-use products and single-use eye drops, as well as ORs that consume high levels of energy, and repeated office visits by patients who need regular monitoring and treatment.

Clearly the environmental cost of practicing medicine is high — and indeed, sustainability isn’t a concept new to ophthalmology. Studies have found that emissions can be largely reduced by incorporating readily available resource efficiency measures. These include optimizing the use of reusable instruments and supplies, maximizing single-use device

reprocessing, promoting minimum waste and recycling practices, using energyefficient appliances and air-handling systems, and investing in low-carbon energy sources.3

But there are barriers, especially in developed countries that can restrict the ability to be more environmentally friendly. For example, flash autoclaving (or immediate use sterile supplies, IUSS) is a process where instrument trays are sterilized but not allowed to dry and is used in India and other countries. This can lower energy expenditures — however, it’s widely prohibited in the U.S., unless specified by the manufacturer. But does this restriction actually make surgery safer?

“Although these regulatory restrictions are made with the purpose of increasing safety, their effect is theoretical and unproven, and they add energy burdens and expense to the process,” explained Thiel, et al. Although most regulations in developed countries are made with patient safety in mind, greater liability in countries such as the U.S. might drive resource use in operating rooms.3

They continued: “Defensive medicine, not based on scientific evidence of infectious risk, adds to the cost and, therefore, environmental footprint of care.”

Another study compared waste generated from glaucoma surgery in the U.S. versus India.4 The authors stated: “The objective of this pilot study is to call attention to the fact that certain regulations in the U.S. lead to the production of potentially unnecessary waste.”

Of course, there’s a caveat: To even begin addressing this issue in the U.S. and other developed nations, it would require rethinking the process of surgical care delivery and restructuring the laws governing the production of medical waste.

Five steps to lower carbon emissions in ophthalmology

So, what can actually be done to help?

The good news is most hospitals and clinics already have some protocols in place to reduce expenses and maximize efficiency while maintaining patient outcomes. And there are also simple things individuals can do to help lower their carbon footprint…

Dr. Redmer van Leeuwen, an ophthalmologist and vitreoretinal

In 2021, Dr. Wee Ling Wong and colleagues published Ophthalmology

Going Greener: A Narrative Review to explore how ophthalmology can reduce carbon emissions, related costs and overall environmental impact, while maintaining a high standard of patient care.2 This paper reminds us of the 5 R’s of sustainability (reduce, reuse, recycle, rethink and research) and how they can be applied in ophthalmic practice without major disruption — as evidenced by Dr. van Leeuwen.

#1 Reduce waste. Turning off the lights and machines in the operating room when it’s not in use can significantly reduce energy consumption. Or finding sensible solutions to reduce waste — especially plastic packaging — can make a substantial impact, as the majority of surgical equipment is not only wrapped in plastic, it’s often double-wrapped.

surgeon at University Medical Center

Utrecht in the Netherlands, spoke with PIE magazine regarding the measures taken to reduce waste at his center. He said that they try to limit the use of disposables in the OR, they ask suppliers for lean custom-packs, and they restrain from using perfluorocarbon liquid (PFCL) and sulfur hexafluoride (SF6) gases as much as possible. “In addition, we shut down air-conditioning when the OR is not in use, and are planning the re-introduction of reusable gowns in the OR,” he shared.

These measures are also recommended by others in the field.

It’s understandable that ophthalmic surgeons might prefer specific equipment for a certain surgical procedure — and as a result, singlepackaged disposable surgical equipment, along with gowns and gloves of different sizes, were born into existence. Herein lies another problem: Unused items (whether it’s tools or textiles) in those prepackaged kits are discarded — which is not only a waste, but a shame as well. The review suggests that doctors could work with industry partners in the “creation of a surgeon-tailored pack with preferred equipment, gloves of their size and disposable gowns, which could reduce the amount of double-packaging of each product.”

Reusable instruments can also greatly reduce waste produced: “Stick to your reusable instruments,” said Dr. van Leeuwen. “Disposables may be attractive in the short-term. But in the end, they are more costly and produce huge amounts of waste.”

Pharmaceutical waste should also be another target to consider to conserve resources and reduce unnecessary waste.

#2 Reuse materials. Reusing materials can be as effective as reducing waste. For example, switching from disposable to reusable surgical gowns in a single hospital led to a waste reduction of 23,000 kg of carbon and saved the hospital $60,000 USD over a 12-month period.2

Clearly, money can be saved by reusing gowns — but there’s always a flip-side. More research is needed on savings, expenditures, as well as potential contamination of reused items. Further, the cost to launder and store these items could render the whole process unsustainable.

#3 Implement recycling programs where possible. Recycling can also be somewhat controversial in medicine, and the ability to segregate waste varies by country. There are also costs associated with recycling to consider. But it can still make a difference: A 2015 study found that recycling did not lead to additional costs — and although the overall impact of recycling and resulting savings were small, it could be magnified if adopted by the national healthcare system.2

This has always been the caveat with recycling: One person dutifully recycling their aluminum cans is unlikely to save the world — but what if 100 million people recycled their cans? This illustrates that really, to make this work — and to make a difference — a big part of the industry would need to embrace a recycling program.

#4 Research best practices. Sustainability in ophthalmology — especially in posterior segment surgery — is an area that needs more research. In particular, data in the following areas would be helpful: the environmental impacts of healthcare activities, life cycle analysis of materials, and cost analysis.

“Innovative design of devices that minimize environmental impact whilst maintaining standard of care would also be useful,” added Dr. Wong and colleagues.

#5 Rethink care for a greener practice. Today, technology can also support a more sustainable practice — especially in vitreoretina, where

the chronic and progressive nature of conditions like age-related macular degeneration (AMD) and diabetic retinopathy (DR) require routine monitoring to prevent deteriorating vision and disease progression.

Thus, creating more localized pathways for care — along with developments in artificial intelligence (AI), telehealth platforms and remote monitoring devices — can help monitor and manage these retinal diseases without the need of repeated office visits.

Ophthalmic gases increase emissions

Along with surgical disposables, Dr. van Leeuwen said that general anesthesia with gas, the use of perfluorocarbon liquid (PFCL), and gas tamponade are the main drivers of carbon emissions in vitreoretinal practice.

Fluorinated gases, including sulfur hexafluoride (SF6), hexafluoroethane (C2F6) and octafluoropropane (C3F8), are used in vitreoretinal surgery to repair conditions like retinal breaks, detachments and macular holes. These are among some of the most potent greenhouse gases, with SF6 identified by the United Nations Framework

Convention on Climate Change (Kyoto Protocol) as one of six gases requiring strict regulation in to reduce global warming.5

“Anesthetic volatile gases (e.g., isoflurane and sevoflurane), fluorinated liquids (PFCL), and ophthalmic gases (SF6, C2F6, C3F8) have an extremely high global warming potential,” said Dr. van Leeuwen. “For instance, global warming potential of SF6 gas is approximately 22,000 times higher when compared to CO2. Moreover, these gases may stay

in the atmosphere for more than 20,000 years.”

To circumvent this issue, Dr. van Leeuwen said that vitrectomy would ideally be performed under local anesthesia with air tamponade.

To investigate, a study published in January 2022 compared the potential reduction in carbon CO2 emissions by utilizing airtamponade (AT) instead of fluorinated gases to manage rhegmatogenous retinal detachment (RRD). The authors included participants from two large tertiary referral vitreoretinal centers where RRDs are exclusively repaired using fluorinated gases (Manchester Royal Eye Hospital (MREH) and Birmingham and Midland Eye Centre (BMEC)) and a tertiary VR center that routinely employs AT in selected RRD

cases (University Hospitals Coventry and Warwickshire (UHCW)).

They found that UHCW used AT in 70% of RRD repairs — this enabled the hospital to “greatly reduce the need for the most environmentally damaging SF6 gas, leading to lower CO2 emissions by 47.0% and 41.1% compared to MREH and BMEC, respectively.”

The carbon footprint of intravitreal injections

Outside of surgical procedures that require gases, intravitreal injections are a very common treatment in posterior segment practice — and they generate a lot of waste. To analyze where emissions may be reduced, Power et al. researched the carbon footprint of a single intravitreal injection (IVT) at Mater Misericordiae University Hospital Dublin in regard to materials procurement, patient travel and building energy use.6

They found that a single IVT (excluding the anti-VEGF agent) was associated with carbon emissions of 13.68 kg CO2eq. The authors shared that this equates to 82,100 kg CO2eq annually for their service. Leading the pollution train in carbon emissions was patient travel (77%), followed by procurement (19%) and finally, building energy use (4%). However, they noted that once an anti-VEGF agent is included, the environmental cost of procurement rises and varies widely at 20, 320 and 423 kg CO2eq per injection for bevacizumab, ranibizumab and aflibercept, respectively.

Harking back to unused items in injection packs: If items considered dispensable by surgeons were omitted, it would cut an estimated 0.56 kg per injection (3,360 kg CO2eq annually). While this speaks to the researchers’ service alone, if extrapolated to the U.K. as a whole, it could save 450,000 kg CO2eq. This is major — and if you’re not quite sure how major — the authors provide this context: A single one-way economy transatlantic flight produces

480 kg CO2eq per person.

Additionally, the authors said that unnecessary single-use plastics from routine procedure packs should also be reduced: “Three of the four dispensable items in our packs are hard plastic … the annual weight of the dispensable plastic in the packs used by our service is over 240 kg.”

What this study shows is that “the far larger contribution of the production, distribution and consumption elements of procurement, compared with the waste disposal element, highlights the need to target emission generation at source.”

Indeed, if the item doesn’t exist — it’s carbon footprint doesn’t either: “The omission of unnecessary items eliminates all of the emissions embedded in the procurement process of an item,” said the authors.

“If sustainability is a goal of the wider ophthalmology community, intravitreal injections, due to their exponential increases in volume, should be a prime target for such efforts,” the authors continued, adding that procurement should be a main focus of such efforts. The authors also point to innovation in drugs and devices — such as longacting agents to reduce the number of IVTs needed — could create more sustainable treatment regimens.

“Clinicians should recognize that they can make simple changes that can have an immediate positive impact on carbon emissions. We must lead by example and address the harmful effects of mindless wastefulness in our daily practice. We strongly advocate bottom-up interventions to drive an overall reduction in carbon emissions in ophthalmology and healthcare as a whole,” the authors concluded.

And these bottom-up initiatives are not only simple, they can be implemented now to lower carbon emissions. But of

course, the first step is recognizing that we have a problem.

“Climate change — or better yet, the climate crisis — is a much bigger threat to humankind than COVID. It has been predicted a long time ago and we notice its effects today, but the longterm consequences will be disastrous,” said Dr. van Leeuwen. “All individuals have to change their behavior, both professionally and privately, in order to avert an uninhabitable earth.”

References:

1. Watts N, Amann M, Arnell N, et al. The 2019 report of The Lancet Countdown on health and climate change: ensuring that the health of a child born today is not defined by a changing climate. Lancet. 2019; 394(10211):1836-1878.

2. Wong, Y.L., Noor, M., James, K.L. et al. Ophthalmology Going Greener: A Narrative Review. Ophthalmol Ther. 2021;10:845–857

3. Thiel CL, Schehlein E, Ravilla T, et al. Cataract surgery and environmental sustainability: Waste and lifecycle assessment of phacoemulsification at a private healthcare facility. J Cataract Refract Surg. 2017; 43(11): 1391–1398.

4. Namburar S, Pillai M, Varghese G, Thiel C, Robin AL. Waste generated during glaucoma surgery: A comparison of two global facilities. Am J Ophthalmol Case Rep. 2018; 12: 87–90.

5. Moussa G, Andreatta W, Ch'ng SW, et al. Environmental effect of air versus gas tamponade in the management of rhegmatogenous retinal detachment VR surgery: A multicentre study of 3,239 patients. PLoS One. 2022;17(1):e0263009.

Contributing Doctor

Dr. Redmer van Leeuwen is a medical retina consultant and vitreoretinal surgeon at the University Medical Center Utrecht, the Netherlands.

Next to his clinical and research activities, he is committed to sustainability in healthcare. Together with Sjoerd Elferink, he founded the Dutch Taskforce on Sustainable Ophthalmology. This taskforce develops guidelines for safe and sustainable procedures in ophthalmology and has an advisory role to the board of the Dutch Ophthalmic Society.

r.vanleeuwen@umcutrecht.nl

6. Power B, Brady R, Connell P. Analyzing the Carbon Footprint of an Intravitreal Injection. J Ophthalmic Vis Res. 2021; 16(3): 367–376.

Dr. Hazlita Dato’ Mohd Isa

Standing Up for Eye-dealism

by Joanna Lee

“My mother said I have a ‘savior complex’,” she said with a warm laugh.

The desire to heal has always driven medical retina and uveitis specialist Dr. Hazlita Dato’ Mohd Isa from a tender age. Anecdotes from her childhood included her attempts at healing dolls and trying to help friends in need.

It was while studying for her medical degree in the University of Glasgow, Scotland, under the tutelage of inspiring ophthalmology lecturers that she gravitated toward treating the eye. “You know they were doing good work and they didn’t really flaunt themselves,” Dr. Hazlita said of her lecturers, one of which was Dr. Ferguson whom she described as well-loved by his patients. “It’s because he didn’t just treat the disease, but he treated the whole person too,” she said.

She also credited the fine examples shown through professors and lecturers at the National University of Malaysia (UKM) where she trained further in her specialty and taught for 16 years.

UKM’s Department of Ophthalmology is mostly womenled, a reflection of Malaysia’s unique situation where a majority of ophthalmologists serving in the public health sector are women.

According to Dr. Nor Fariza

Ngah who is the President of College of Ophthalmologists, Academy of Medicine Malaysia, “Out of the 715 ophthalmologists we have, 55% are women overall, while 75 male and 302 female ophthalmologists work in the Ministry of Health.”

“Imagine the beginning of the year where many of us competed for time off to settle our children in school,” Dr. Hazlita said of working in a mostly female environment. “I suppose ophthalmology is slightly more forgiving

in terms of time as we have fewer emergencies in the middle of the night compared to our surgical colleagues. However, the workload is quite on par with the other specialties,” she said.

Love what you do

The pursuit of medicine is not as glamorous as many think. “It is a vocation and you need to love it. The work is hard.

“With constant interactions among patients, and the need to relate with various characters and personalities on the job, you sort of need to be a people person as well,” she said.

For women in particular, the challenges remain in juggling between work and family, what with being on call and working long or erratic hours in a male dominant field like medicine. “I’m not sure if it’s fair to say that men don’t face the same sort of challenges as women do. But women do face limitations if they want to do certain things. If men want to do certain things, they can just do it. But for women, like for Muslims, they have to ask permission from their husbands, while some are expected to get the house sorted out first beforehand. So, these are some of the challenges we face.”

Having said that, Dr. Hazlita said she’s been very fortunate in terms of receiving support. “I have very good parents, siblings who are also in the medical field, and my husband, although he’s not in the medical field, is very supportive and very understanding.

“But you still have that maternal instinct and sense of responsibility as a female ingrained in us, and that might limit us in that sense,” she said.

The mother of four related one of the toughest

instances she faced early in her work when she was pursuing her master’s program. “With high expectations, you had to prove yourself and constantly improve. In a six-month period, you’re only allowed 14 days off including medical and emergency leave.

“Here, I was trying to start my career, and at the same time start a family. If I took more than 14 days of leave, I’d have to extend for another six months. You have to plan for your family and personal life while trying to pursue your career, which men don’t go through.”

A champion for autism awareness

The greatest challenge for her yet arrived when her youngest baby fell ill during the time she pursued her PhD. “When you pursue your career in medicine, you don’t have the luxury of taking a month off. But I suppose that’s a choice and you could, but it would delay you. So, that to me was hard,” she said.

“And when we found out he had autism at one-and-a-half years old, having to cater to his needs while working to become a doctor was difficult, too, as I needed time to ensure he received the right therapy.”

At that point in time, she and her husband were in the U.K. Searching for limited information on therapy and support systems in Malaysia nearly 13 years ago was not easy. Upon their return, she wanted people to become more aware of autism. “I was not embarrassed about it and told everyone what he has as opposed to hiding it. Some parents were afraid to be open due to the fear of being stigmatized, but I never wanted that.”

She champions for better therapy and treatment for children with autism by communicating with and helping teachers and parents understand how to deal with issues surrounding caring for them.

“Early intervention is key to help these children along with parents’ awareness and acceptance of their child’s condition,” she expressed.

This was one of the reasons she transitioned from her career in public service to a private practice which gave her more flexibility in time. Her only regret was she wasn’t able to give fuller attention to her three older children during that period.

Dreams for the future

As bold and vivid as the colors of her self-painted acrylic masterpieces lining her clinic’s walls, Dr. Hazlita’s passion for helping those who can’t runs deep.

One of her dreams is to eventually have the means to be able to help underprivileged patients without expecting anything in return. “I would love to ‘heal unconditionally’. I want them to have access to quality treatment even if they can’t afford it, or as much as they can afford,” she said. “Even if all they could pay me in return is with durians, go ahead,” she jested. Dr. Hazlita strongly believes that there shouldn’t be any discrimination in the sense of prioritizing one patient over another in the queue based on socioeconomic status or titles.

She is currently running her own clinic during the weekends, even operating on

Sundays, where appointments can last until 6 p.m. “I love seeing patients,” she said, explaining it’s not about making more profit, but more about her concern for elderly patients who don’t usually have follow-ups because their children are too busy to bring them for check-ups. “So now, nobody has excuses anymore for not bringing their parents in for consultations!” she said.

These days, she looks forward to more quality time with her family while finding ways to treat more needy folks. For women deciding to pursue medicine and ophthalmology, and in general, she said: “Be brave and always have your chin up.” For after the storms, she’s one who would like to leave some rainbows behind.

Contributing Doctor

Dr. Hazlita Dato’ Mohd Isa MBChB (UK), MSOphthal(UKM), AM(Mal) is a specialist in medical retina and uveitis at Gleneagles Hospital, Ampang, Kuala Lumpur, while also managing general problems such as cataract, glaucoma, dry eye, contact lens-related eye disease, lid lesions, refractive error and more. She graduated from the University of Glasgow, Scotland, U.K., and subsequently obtained a Doctorate of Ophthalmology (DrOph) at the National University of Malaysia (UKM). Thereafter, she completed a PhD in ophthalmology at the University College London, U.K., as well as a fellowship in uveitis and medical retina at the renowned Moorfields Eye Hospital, London, U.K. She was previously an associate professor and consultant ophthalmologist at the UKM Medical Centre (UKMMC), Kuala Lumpur, and head of the uveitis and medical retina unit in the Ophthalmology Department UKMMC, where she has taught and mentored medical students and young ophthalmologists who are now currently serving the nation. Dr. Hazlita is also regularly invited as a speaker at various international and local ophthalmology conferences and has also published numerous articles in both local and international journals.

drhdmi@yahoo.co.uk

YouTube for Ophthalmic Content Friend or Foe?

by Chow Ee-Tan

Online videos for sharing medical knowledge and procedures — and their quality and utility — have received more attention in the last couple of years, especially during the COVID-19 pandemic when many countries went through lockdowns of various degrees.

YouTube, being the largest and most used video-sharing website worldwide, has the potential to disseminate medical information and opportunities for medical learning.

Some medical studies have reported that YouTube is currently the main platform used by surgeons to prepare for surgical

procedures,1-2 including vitreoretinal surgery.

Drawbacks of YouTube for surgical study…

Traditionally, surgical training has always been face-to-face between a mentor and his trainees — and many of these surgical techniques involve complexity. Surgical videos on YouTube are tools that can be useful and appropriate to complement surgical learning, provided the content has an educational purpose and the video has good quality and detailed explanations.

It is difficult to adopt control and validation measures for surgical videos on YouTube and other social media platforms. Their quality, utility and reliability are questionable as the content can be posted by any surgeon whose background may not be known, without a review and quality-control process.

Many recent scientific studies on the reliability of YouTube videos in vitreoretinal surgery have come to the conclusion that those videos were of low quality and reliability, and recommend the need for a standardized system on how to present retinal surgical videos on the internet.

“Videos posted to the public domain on different social media, most often YouTube, are widespread and unregulated for providing complimentary surgical education. Retinal societies should formulate guidelines and improve the educational value of the surgical videos posted on the internet,” concluded a report entitled Evaluation of quality and utility of YouTube vitreoretinal surgical videos published in International Journal of Retina and Vitreous 3

The study evaluated the utility and quality of surgical videos posted on the main retina YouTube channels by surgeons at different career stages and assessed how well the steps of the

vitrectomy videos conformed to the parameters in the Casey Eye Institute Vitrectomy Indices Tool for Skills assessment (CEIVITS) scale.

Forty-five videos were included from nine retinal YouTube channels posted from 2011 to 2021. For each surgeon, 10 videos were randomized and the utility, quality and educational content were assessed. For each video, the surgeons also assessed how the validated CEIVITS items were presented in the videos. The surgeons were divided based on years of experience: fellows (0-3 years), young surgeons (4-10 years), and senior surgeons (more than 10 years).

The fellows presented a detailed assessment of the quality and utility of vitreoretinal surgical videos in the public domain and available on YouTube based on the perspective of the surgeons at different career stages. The topics most frequently addressed in the sample were rhegmatogenous retinal detachments, macular holes, and intraocular lens implantation in the absence of adequate capsular support.

The study found that the video image quality was rated as good in 63.52% of evaluations, moderate in 30.37%, and poor in 6.11%. The quality assessment of the videos among the groups did not differ.

“The learning curve associated with vitreoretinal surgery can be long and requires the development of key surgical skills. Medical professionals today have access to several tools, and the use of online resources has become part of the educational process.2

“Surgical videos are an example in which the combination of figures, captions and diagrams can be added to facilitate learning. A wide range of free online retinal surgical videos is available on different social media sites, which provides access to information in a fast, practical, and inexpensive way, and eliminates the limitations imposed by geographic and time barriers,” the study quoted.4-5

…and the benefits

On the positive note, it states both experienced surgeons and trainees can benefit from watching surgical video content, either to review a rarely performed procedure, improve technical details, or discover different solutions that other colleagues have performed.

Analysis from the study shows more inexperienced surgeons (fellows or those with careers shorter than 10 years), reported significantly greater use of videos than experienced surgeons (with careers longer than 10 years). The average utility score in this group was 3.47 on a scale of 1-5. The general average of the study sample was 3.83. Similarly, the analysis of the educational content found that the fellows learned something new from the videos 34.76%

of the time (p < 0.05), and the more experienced surgeons reported learning something new 19.17% of the time.

Standardization is needed

Meanwhile, a rate of 26.85% for controversial and/or inappropriate content was found in the videos. The study suggests that important measures to standardize the editing and the content of these videos should be studied and published to reduce the chances of including educationally inappropriate materials.

There is a need for a standardized system on how to present retinal surgical videos on the Internet. International committees can meet to publish a consensus to guide creation of highquality educational videos.

Another study entitled Reliability of YouTubes Videos in Vitreoretinal Surgery6 published online on September 1, 2021, investigated the reliability and quality of vitreoretinal surgery videos posted to YouTube.

The researchers searched with keywords “vitrectomy,” “retinal surgery,” and “vitreoretinal surgery” on YouTube and took into account total view counts, numbers of comments, likes and dislikes, publishing dates, and source of videos were recorded. Educational quality and accuracy of the video content were evaluated using the DISCERN score, Journal of the American Medical Association (JAMA) scoring system, and Global Quality Scores (GQS).

There were 208 videos included in

the study: 152 (73.1%) videos were uploaded by doctors and 56 (26.9%) videos uploaded by non-doctors. Mean DISCERN, JAMA, and GQS scores were 37.65 ± 10.49 (20-69), 0.82 ± 0.52 (0-4), 2.86 ± 0.86 (1-5), respectively.

The study came to the conclusion that “vitreoretinal surgery videos on YouTube were of low quality and reliability. Those who want to use YouTube videos as a reference for vitreoretinal surgery should pay extra attention to selection of content.”

Meanwhile, a study entitled Evaluation of the Usefulness of YouTube Videos on Retinal Detachment Surgery7 was published on November 10, 2021 to specifically evaluate YouTube videos on retinal detachment surgery.

One hundred videos were scanned using the keyword “retinal detachment surgery” in the YouTube search engine. These videos were analyzed and also scored using DISCERN, Journal of the American Medical Association (JAMA), and Global Quality (GQ) scoring systems.

Results show that the DISCERN score of the evaluated videos was 39.5±8.4; the JAMA score was 1.9±0.5; and the GQ score was 2.1±0.5. According to the results, retinal detachment surgery videos, DISCERN score is medium, the JAMA score was evaluated as low quality, and poor quality in the GQ score.

The study concludes that “YouTube videos labeled ‘retinal detachment surgery’ often contain poor content quality and incomplete information.” It adds that in order for these videos to be used as a source of information, they should be “recorded by more qualified

professionals, presenting their content and all information about all treatment options, complications, and healing processes in an objective way.”

It states that the rise in published studies on YouTube, video reliability is proof that increased opportunity has led to the increase and dissemination of false and even harmful information.

However, the researchers admitted the limitation of the study. There wasn't enough information about the preand postoperative videos that they considered surgical, and the videos evaluated were only in English. Thus, further studies are needed to accurately evaluate YouTube videos for retinal detachment.

References:

1. Mota P, Carvalho N, Carvalho-Dias E, et al. Video-based surgical learning: improving trainee education and preparation for surgery. J Surg Educ. 2018;75:828–35.

2. Rapp AK, Healy MG, Charlton ME, et al. YouTube is the most frequently used educational video source for surgical preparation. J Surg Educ. 2016;73:1072–6.

3. Lucatto LFA, Prazeres JMB, Guerra RLL, et al. Evaluation of quality and utility of YouTube vitreoretinal surgical videos Int J Retina Vitreous. 2022;8(1):9.

4. Udawatta M, Ng E, Westley Phillips H, et al. Age-related differences in social media use in the neurosurgical community: a multi-institutional study. Clin Neurol Neurosurg. 2019;180:97–100.

5. Pape-Koehler C, Immenroth M, Sauerland S, et al. Multimedia-based training on Internet platforms improves surgical performance: a randomized controlled trial. Surg Endosc. 2013;27:1737–47.

6. Sayin O, Altinkaynak H, Adam M, Dirican E, Agca O. Reliability of YouTube Videos in Vitreoretinal Surgery. Ophthalmic Surg Lasers Imaging Retina. 2021;52(9):478-483.

7. Songur M, Citirik M (November 10, 2021)

Evaluation of the Usefulness of YouTube Videos on Retinal Detachment Surgery. Cureus 13(11): e19457.

Staging and Managing Myopic Traction Maculopathy

by Tan Sher Lynn

Italian vitreoretinal surgeon Dr. Barbara Parolini presented a new staging system and guidelines for the management for myopic traction maculopathy (MTM) during the LV Prasad Eye Institute (LVPEI) Vitreoretinal Surgery Masterclass 2022 webinar.

Pathogenesis of MTM

Myopic traction maculopathy (MTM) is a complex disease affecting approximately 30% of eyes with pathologic myopia. Its pathologic features may also include lamellar or full thickness macular holes (FTMH), shallow foveal detachments and inner retinal fluid.

“In a normal situation, there is the centripetal force that points to the fovea and keeps the retina together. This force is due to the combination of

neural cells, external limiting membrane and internal limiting membrane. In MTM, various centrifugal forces play against this centripetal force. The forces perpendicular to the retina induce schisis and detachment; while the forces tangential to the retina induce foveal splitting,” said Dr. Barbara Parolini.

She further explained that the centrifugal force from the posterior eyewall elongates the eye posteriorly and detaches the sclera from the retina. Meanwhile, the centrifugal force from the lateral eyewall enlarges the eye and induces detachment in the lateral part of the eye. Centrifugal force from the vitreous pulls the retina anteriorly, and centrifugal force from the interface (tangential to the retina) leads to FTMH.

“The forces can also be combined. You can have centrifugal perpendicular force

(from the eyewall and vitreous) and centrifugal tangential force (from eyewall and vitreous) and you will end up with a macular detachment combined with macular hole,” she noted.

The MTM staging system

To improve the diagnosis and management of MTM, Dr. Parolini and her colleagues published the MTM Staging System (MSS), which is a comprehensive description of OCTbased classification of MTM.*

“The study of the natural history of MTM demonstrated that MTM is divided not in types but in stages. Stage 1 refers to inner-outer macular schisis, stage 2 is predominantly outer macular schisis, stage 3 is macular schisis and detachment and stage 4 is complete

macular detachment without schisis because the inner forces are released. Within these four stages, there are three stages of the fovea — stage a: normal foveal profile, stage b: tangential evolution in lamellar macular hole (LMH) and stage c: tangential evolution in FTMH,” Dr. Parolini explained.

She noted that the MSS serves as a base for definitions and prognosis, as well as a guideline to treatment.

“If you have a patient in stages 1a and 2a, I advise you not to do anything because the evolution is very slow and visual acuity is good. You can ask the patient to come back in 12-18 months. For stage 1b and 1c, I advise vitrectomy but for 1b, only if vision is declining. For stage 3a and 4a, just do macular buckling. Do not touch the retina from the inside. For stage 2b, 3b and 4b, I advise to apply macular buckle and add vitrectomy as the second step only if the lamellar hole remains symptomatic. For stage 2c, 3c and 4c, I advise to perform macular buckling and pars plana vitrectomy (PPV).

“In summary, retinal patterns, such

as schisis and detachment, should be solved by a macular buckling because perpendicular forces should be pushed. While foveal pattern (holes) should be solved by PPV, as tangential forces should be peeled,” she said.

She further explained that when there is a centrifugal force detaching the scleral from the retina, the way is to push the scleral to the retina with the macular buckle. Meanwhile, if there is a macular hole, it should be treated with vitrectomy and internal limiting membrane (ILM) peeling. When combined forces are present, treatments should be combined as well.

Inserting the macular buckle

The macular buckle is a device made to shorten the axial length at the posterior pole.

“If you are using just the macular buckle, I advise to start with paracentesis to lower the intraocular pressure. The easiest quadrant to insert the macular buckle is the superotemporal quadrant,

where you can easily reach the fovea since there are no oblique muscles,” Dr. Parolini suggested.

“Use the panoramic viewing system to locate the buckle. Centration is a key factor in this type of surgery. Sutures can be applied anteriorly close to either the lateral rectus muscle or superior rectus muscle. You can use one or two sutures to fixate the buckle and avoid tilting.”

She showed a case of MTM with stage 4c detachment and full thickness macular hole, and the patient’s vision was counting fingers. “If you do a vitrectomy with such a huge staphyloma, you will have a good chance to attach the retina under gas and keep the hole open, but when the gas is removed, there’s a high chance that the retina will re-detach. Putting in silicone oil can attach the retina, but when the oil is removed, the retina will re-detach. On the other hand, the application of a macular buckle with vitrectomy gas and ILM peeling can achieve an attached retina, a hole that is closed, and an increase in visual acuity,” she said.

“My suggestion is to follow the MSS classification system and guidelines of treatment. Choose the model of buckle you prefer, and help me validate the MSS,” she concluded.

Editor’s Note:

The LV Prasad Eye Institute’s Vitreoretinal Surgery Master Class, aptly titled “Tough case or a surgical surprise, let’s learn the enterprise” was held from February 26 to 27, 2022. A version of this article was first published on piemagazine.org

* Parolini B, Palmieri M, Finzi A, Besozzi G, Lucente A, Nava U, Pinackatt S, Adelman R, Frisina R. The new Myopic Traction Maculopathy Staging System. Eur J Ophthalmol. 2021;31(3):1299-1312.

holes.

Retina, and the All-Important Macula

E-Poster Highlights from RANZCO Virtual 2022

by Tan Sher Lynn

The macula represents a small part of the retina but it is essential for clear vision. Australian researchers shared their findings related to the macula through e-poster presentations during The Royal Australian and New Zealand College of Ophthalmologists (RANZCO) 52nd Annual Scientific Meeting. We continue to cover some interesting posterior segment related e-posters presented during the congress…

Impact of cuticular drusen on vision

Cuticular drusen represent a phenotype of clinical relevance in the spectrum of age related macular degeneration (AMD) and may confer a higher risk of progression to vision-threatening complications. To determine the prognostic significance and impact on visual function of the cuticular drusen phenotype in intermediate AMD, Dr. Kai Lyn Goh from the Centre for Eye Research Australia and colleagues examined 280 eyes from 140 participants with bilateral large conventional drusen.

The patients underwent color fundus photography (CFP), optical coherence tomography (OCT), fundus auto fluorescence and microperimetry testing at baseline, and then once every 6 months for 3 years. These eyes were graded for the presence of cuticular

drusen, based on characteristic changes on CFP and OCT – multiple yellow, small, uniform, round deposits on CFPs corresponding to a series of retinal pigment epithelium elevations on OCT.

“There are three important things we noted about patients with cuticular drusen. First, those with the phenotype did not show increased progression to late AMD over 3 years. Second, there is no significant difference in baseline visual sensitivity between those with and without cuticular drusen. And third, those with cuticular drusen did not show a greater rate of visual sensitivity decline prior to the development of late AMD compared to those without this phenotype.

“These findings suggested that those with cuticular drusen have a similar prognostic significance as those with conventional drusen and should be managed accordingly,” she noted, adding that further work is needed to understand the unique disease pathways in the development of cuticular drusen which will likely inform the best treatment strategies for the phenotype.

Nocturnal hypoxia and AMD

Our eyes have millions of photoreceptors that are highly metabolically active, especially at night, and are vulnerable to AMD. Dr. Wendy Fang from Monash

University explored the possible role of nocturnal hypoxia in AMD.

She and colleagues did a study which measured nocturnal oxygen levels in a cohort of 98 AMD cases and 47 age-matched controls using a pulse oximeter over three consecutive nights. Parameters measured included: oxygen desaturation index (ODI), basal peripheral oxygen saturation (SpO2), minimum SpO2, range of SpO2 and percentage of time spent below 90% SpO2.

“We found that AMD was not significantly associated with any of these parameters. Results are inconclusive and the reason could be that our study was underpowered due to sample size. Therefore, increasing the cohort size will be important and we can continue to explore this novel, potentially modifiable risk factor for AMD,” she said.

Macular cell loss in rodcone dystrophy

Gene therapy has emerged as a novel treatment strategy for inherited retinal diseases (IRD). However, measurement of treatment efficacy is limited by traditional clinical trial endpoints such as best corrected visual acuity (BCVA), according to Dr. Joel Mudri from the Royal Perth Hospital, Western Australia.

To investigate this, he and his colleagues

did a prospective, observational cohort study to quantify the progression of total macular volume (TMV) in patients with rod cone dystrophy over a two-year period compared with the traditional endpoint of BCVA. They also aimed to determine the feasibility of using TMV change as endpoint in clinical trials and assess the symmetry in progression rate between eyes.

During the study, the patients underwent baseline ophthalmic examinations including BCVA test and spectral domain (SD)-OCT with the Heidelberg Spectralis HRA+OCT and were followed-up every 6 months for a minimum of 2 years.

“We found that in one third of cases, TMV decline exceeded the retest variability. The feasibility of using TWV as an endpoint for clinical trials is limited by coexisting pathology (e.g. cystoid macular edema, epiretinal membrane, macular hole and gliosis). While progression of TMV between eyes is highly symmetrical,” he said.

360-degree laser retinopexy in primary vitrectomy

Single surgery anatomical success (SSAS) is a main outcome in primary rhegmatogenous retinal detachment (RRD) repair. As the risk of recurrent detachment and poor functional outcomes increase with subsequent procedures, the use of 360-degree prophylactic endolaser photocoagulation has been proposed to reduce redetachment rates. Dr. Matthew Peters from The Royal Brisbane and Women’s Hospital (RBWH) investigated the use of 360-degree laser retinopexy in the treatment of RRD.

The study involved 190 RBWH patients who underwent primary pars plana vitrectomy (PPV) with or without scleral buckling (SB) from June 2017 to December 2020. Patients were divided into the 360-degree laser group (n=130) or limited laser retinopexy group (n=62).

The researchers found significant association of the 360-degree laser use with worse preoperative LogMAR visual acuity, male sex and higher grade of proliferative vitreoretinopathy (PVR). “360-degree laser was more likely to

be applied in patients with more severe disease and worse prognosis and is part of more extensive operations. Even accounting for these factors, there is no significant difference in SSAS, final LogMAR visual acuity or complication rates between 360-degree laser and limited laser groups,” Dr. Peters said.

Correlation between retinal ganglion cell layer thickness

Retinal microvascular and structural changes may precede cognitive symptom onset in Alzheimer’s disease (AD). Using them as biomarkers may allow early identification of asymptomatic individuals at risk of AD, noted Dr. Samran Sheriff from Macquarie University, Sydney.

Dr. Sheriff and colleagues did a study to evaluate the correlations between retinal ganglion cell layer thickness (RGCL) and various domains of neuropsychological testing (Mini Mental State Exam [MMSE] and Symbol Digit Modality) in 95 healthy aging subjects recruited from the Optic Nerve Decline and Cognitive Change study.

“We found that the MMSE correlated with the Global RNFL (β = -4.409, p = 0.04), temporal superior RNFL (β = -11.2, p = 0.002), and naso-superior RNFL (β = -9.44, p = 0.002). The nasal superior region analysis also correlated with Symbol Digit Modality (β = 8.300, p = 0.002). This preliminary data supports the idea that the changes in retinal ganglion cell layer thickness correlate with specific neuropsychological domains,” he said, adding that future research will unravel whether a stronger statistical relationship between RGCL thickness and specific neuropsychological domains exists in dementia and psychiatric disorders.

Automated detection of glaucoma from retinal fundus images using different fundus cameras

also be used to screen for glaucoma. Nearly 30 retinal fundus cameras from different manufacturers are currently in use, such as the ZEISS VISUCAM 500, Canon CR-2 and Topcon TRC retina camera, according to Dr. James McKelvie from the University of Auckland, New Zealand. He and colleagues set out to evaluate the accuracy of automated glaucoma detection from retinal fundus images obtained with different fundus cameras.

The experiment was conducted in three steps: The researchers first cropped the images around the optic nerve head. Then, they extracted features using pre-trained deep neural network. Finally, they trained an AI model using a fundus camera and tested it with another fundus camera.

They noticed that an average accuracy of 96% was obtained when train and test images are from the same camera. However, the average accuracy dropped to 52% when train and test images are from two different fundus cameras. The authors concluded that while AI based automated detection of glaucoma from fundal images is possible, AI models trained on one camera may have greatly reduced accuracy in grading images obtained from other cameras. Hence, they suggested that for clinical use, AI model accuracy needs to be reassessed for each camera type, and designing domain generalized glaucoma detection models will improve the robustness of these systems.

Editor’s Note:

The 52nd Annual Scientific Congress of The Royal Australian and New Zealand College of Ophthalmologists (RANZCO Brisbane 2022) was held virtually from February 26 to March 1. Reporting for this story took place following the event. A version of this article was first published on piemagazine.org

Retinal fundus images are routinely used for diabetic photo screening and may