Pathos Ocularis-the Beautiful and the Curious, is a fascinating exhibition at the College of Optometrists in London which merges art with ophthalmology.

Almond shapes, long eyelashes and interesting irises-in particular those with several colours and patterns: these are what make beautiful eyes, according to artist and glassmaker IluÃ¡ Hauck da Silva. “However,” she says, “ultimately it is the intensity and sincerity of gaze which makes a pair of eyes beautiful: eyes that sparkle with enthusiasm and love, and that overflow with tears when emotion takes over. The ability to candidly and transparently express feelings is definitely the most fascinating and beautiful quality eyes have.”

The crux of Miss Hauck da Silva’s practice is to visually investigate the human condition, and she specialises in works of anatomical and pathological symbolism (see Figure 1). It is eyes, specifically, that she has dedicated her latest work to, following her artist-in-residence at the College of Optometrists in London, UK in 2019.

At the College’s museum-the British Optical Association Museum-she has created a fascinating modern-day cabinet of eye-related curiosities, complete with drawings, photographs, digital images and glass objects, all of which can be viewed by the public.

In producing Pathos Ocularis-the Beautiful and the Curious, the title of the exhibition, Miss Hauck da Silva took inspiration from the Museum’s collections, as well as from medical, scientific and historical research she conducted in the College library (which contains literature on the eye and optical science dating back to the 15th century). She combined her research findings and artistic expertise with facets of her own experience with eye disorders.

Glass eyeballs feature largely in the exhibition. In Eyeconography (Figure 2), an antique silver dish designed to look like a chalice holds a dozen or so exquisitely made but not so healthy-looking eyeballs-each a glossy white with irises in vivid blues, oranges and greens-and some with a double pupil or iris, to represent the double vision that the artist has herself experienced.

Describing her experience with diplopia, Miss Hauck da Silva told Ophthalmology Times Europe: “I suffered from diplopia as a result of sixth nerve palsy, which occurred due to the fact that I had an infection in my petrous bone [which I had] for at least 6 weeks before my sixth nerve was affected. In a way, I am glad I had diplopia because it was the symptom that urged me to seek help at Moorfields Eye Hospital [London]. Double vision was rather disorienting and deeply concerning-I remember feeling very fragile and vulnerable.”

Once hospitalised at Guy’s Hospital, London and medicated, Miss Hauck da Silva’s diplopic symptoms quickly subsided, but it took at least 3 months for the movement in her right eye to return to normal. Ever since the infection, she has suffered from dry eyes and photophobia, which worsen if she has to work on a computer for long periods of time, use her mobile phone a lot or travel on public transport. She finds these symptoms both “uncomfortable and frustrating”.

Miss Hauck da Silva is also an art historian and considered Saint Lucy, the patron saint of the blind in Roman Catholicism, when producing the show. “When I first saw the Museum’s cabinet drawers full of glass eye models representing ocular pathologies in advanced stages, I immediately made a connection with Saint Lucy’s eyes on a plate, her principle iconography, which suddenly resonated very differently with me,” she described.

“I was compelled to think of people from bygone eras who would leave votive offerings or ex-voto on altars dedicated to Saint Lucy either in hope to be cured or in gratitude for having been cured. Such people could have been suffering from those advanced ocular pathologies represented in the glass models-glaucoma, cataract or an eye infection-when there was no medical treatment for such conditions. It must have been truly awful!”

She added: “This called into question the role of the cult of saints before the advent of modern medicine, and how our attitudes towards illness and cure have changed since then. This is why, in my Self-portrait as Saint Lucy (Figure 3), instead of eyes I have placed images of the medication that cured me from acute diplopia on the plate, conflating the religious and the scientific.”

According to Miss Hauck da Silva, the most validating moment of her art residency was when she first told Neil Handley, curator at the Museum for the past 22 years, that whilst doing research in the Museum’s library, she had come across a chapter in a book that had been written by the very doctor who had treated her when she suffered from diplopia/sixth nerve palsy. This is when Mr Handley said she should make her work about the illness she had, since sharing her personal experience would potentially make it easier and more interesting for viewers to relate and engage with the show.

Mr Handley, who has a background as an historian of science and medicine, first encountered the artist as a visitor to the Museum. “Her obvious interest in our collections, coupled with fortuitous timing-it had been 7 years since our last artist-in-residence-meant she was an obvious person to approach,” he said.

“Her work is also very visual, but not abstract, which suits the general flavour of our displays, which our founder John Sutcliffe instigated as far back as 1901 (we are the oldest optical museum in the world). Sutcliffe commented that he wanted there to be eyes looking at you from every corner of the professional headquarters (then at a different location, but we’ve continued the theme in our present building) so that no one who crossed the threshold could be in any doubt as to the subject matter of the optometry profession,” he added.

“It’s appropriate, therefore, that IluÃ¡’s exhibition is in the reception area, making it the first thing that visitors to the College see.”

Mr Handley explained that all the College’s exhibitions are a challenge, because they have to operate on a very small scale due to their location in what were formerly domestic premises, albeit a pair of very nice Georgian town houses. He said: “Our first-ever artist-in-residence, Derek Ogbourne, produced a ‘micro’ exhibition within a single pull-out drawer, whereas our second, Patrice Moor, produced an exhibition comprising just three works, placed strategically at intervals within the permanent display.”

He added: “I decided to offer IluÃ¡ one entire display case, but she was governed by its dimensions and the fact that all the works would have to be displayable in the horizontal position. IluÃ¡ obtained great insight from holding discussions with our Clinical Adviser at the College, Mr Daniel Hardiman-McCartney. It was a learning journey for her as much as for us, in that she learned a lot more about her own eye condition and how others have coped with eye disease or visual impairment over the centuries.”

For Mr Handley, the lived experience that manifests in the exhibition is a highlight. He says: “I like the assemblage of pieces collectively entitled Dry Eyes [see Figure 4]. The aim was to represent, in artistic form, just what experiencing an eye condition feels like. That’s quite a challenge, but IluÃ¡ has succeeded; just looking at the pieces is painful.”

“Their rough, gritty surface texture took multiple firings to perfect and it was quite a lengthy process to achieve the end result, in the same way that treatment for a medical condition can often take a long time and bring its own pain in the process.” For this piece, the artist chose to move away from anatomically correct eyes to a two-dimensional form inspired by ancient Egyptian imagery.

Although her story is told ultimately as a positive one of recovery, Miss Hauck da Silva pointed out: “I wanted to include the word pathos in the exhibition title, as in many languages it evokes suffering and pain, and thus prompts empathy/compassion in the viewer for the sufferer.”

The Museum hopes that visitors to this show will respond to both the beauty and the curious nature of the exhibits. These concepts are not mutually exclusive. Some of the imagery may subvert commonly accepted notions of beauty, and some of the most curious things, including pathological conditions, can convey a strange beauty of own.

It is often suggested that the works of art in an exhibition will ‘speak for themselves’. For this show, Mr Handley said he wanted to allow the voice of the artist to be heard much more explicitly-and the College has certainly succeeded in this, for these exhibits ‘see for themselves’.

The exhibition will be available to visit by appointment at The College of Optometrists, London, once the lockdown restrictions currently in place due to the COVID-19 pandemic have been lifted. For more information, visit www.college-optometrists.org.


	MISS ILUÃ HAUCK DA SILVA
	E: ihauckdasilva@gmail.com
	Miss Hauck da Silva is an artist whose practice focuses on visually investigating the human condition. She specialises in works of anatomical and pathological symbolism.

MR NEIL HANDLEY
	E: museum@college-optometrists.org
	Mr Handley is the current curator of the British Optical Association Museum and the first full-time museum professional to hold the post.

Articles

The beautiful and the curious: Artwork of ocular pathologies

The educational goal of e-learning is to not to replace conventional hands-on experiences but to improve the quality of refractive surgery training worldwide, since learning is a non-stop process.

Living in an era of vast technological development has shifted the way we learn. Teachers and students no longer need to be physically present at the same time and place, but can instead engage from afar and this form of online learning, or “e-learning”, is increasingly becoming more the norm. Traditional learning still has an important role, however, and remains essential in maintaining the learning process.1,2

The concept of distance learning is not new; there is historical evidence as to its existence as far back as the 19th century, courtesy of Sir Isaac Pitman, who taught a system of shorthand in the 1840s for students living abroad, which was a method of exchanging mailing texts.3 There are many definitions for e-learning (also referred to as E learning, online training and online learning); however, broadly speaking, experts agree that it involves the electronic delivery of training or education and requires interaction with the Internet or other computer network via a computer or electronic device such as a mobile phone.4-6

Many ophthalmologists seek continuous medical education in order to achieve personal growth and career development, especially when dealing with one of the most continuously advancing fields such as refractive surgery. However, for those with a full-time job or families, online learning becomes a particularly attractive proposition. For instance, it allows them to take care of their home and children during the day and study at night, making distance learning highly advantageous over the traditional educational system.

Overall, the benefits of e-learning are many, including “cost-effectiveness, enhanced responsiveness to change, consistency, timely content and flexible accessibility”.5,6 Moreover, e-learning technologies provide students with more control over the learning process in terms of content and pace of learning, which allows them to modify their experiences according to their individual learning objectives.

E-learning also enhances communication between those engaging with it by making open discussion panels possible. Since responses within e-learning can be made around the clock, students tend to be more highly motivated and more involved in the learning process2. In addition, there are no geographical barriers, making this style of learning accessible to doctors worldwide.

Drawbacks of online courses include the limited emotional and personal interactions that take place, although this can be partially overcome by engaging in video conferences and live discussions. Another consideration is the ongoing expenses incurred by students, whilst those who create and need to maintain the courses also need to set aside a budget.

Moreover, participants need to have a good sense of self-discipline and time management in order to follow course timelines, which indeed may interfere or overlap with working hours or night times as they may take place in countries with different time zones.5,6 These factors can make compliance with attendance more challenging.

Another challenging feature of e-learning is that surgical skills have to be acquired by observation rather than through a hands-on approach available with traditional methods of teaching. A lack of reliable assessment after each lecture or course can be another issue with e-learning programmes.

Continuous medical education is considered compulsory for ophthalmologists to ensure that knowledge and skills are regularly updated. Due to growth in educational technologies, the e-learning resources that have become available to ophthalmologists worldwide has significantly increased.

Examples of major providers are: the International Council of Ophthalmology, the American Academy of Ophthalmology, the Asia-Pacific Academy of Ophthalmology, and Cyber Sight. Moreover, social media (such as Facebook, Twitter and LinkedIn) play some role in providing medical news feeds.

However, it is important to build the most effective online courses and provide a trusted source for continuous ophthalmic education, especially in subspecialty training with known syllabuses and flexible timelines.

E-learning in cataract and refractive surgery

We are still facing some limitations and scarcity in the field of refractive training, especially in relation to residents and young ophthalmologists. Most of their knowledge is provided through humble training or some courses they attend during international or regional conferences.

This is where online courses are important, since they provide in-depth theoretical training with flexible timelines without the need to leave their jobs and families. Such courses are given by the most prominent and well-respected figures in the field.

Moreover, these courses are not biased towards certain technologies. Such bias might be seen in other workshops or courses that are provided by companies wishing to highlight their products and any new technologies in the field of refractive surgery.7 Therefore, we can spread healthy practice policies and provide unbiased answers to ophthalmologists everywhere.

Refractive surgery online training programmes

There are four online courses in refractive surgery that were designed specifically to provide intensive specialty training, with a diploma or certificate awarded at the end of the course:

1) The Scientific Methodology in Cataract, Refractive Surgery and Corneal diseases, Miguel HernÃ¡ndez University, Alicante (Spain)8, is a 25-credits programme containing six modules, which are conducted over the period of one academic year. The course is two semesters long, and an official university certificate is issued on its completion.

The material for this course is prepared by a team of national and international professors and consultant ophthalmologists, providing a comprehensive learning channel that covers all aspects of modern refractive surgery science. The expected average of weekly educational activity required is 6 hours, depending of the learning base of the student; communication with the teaching faculty can take place at any time via email or direct communication to cover any difficulties the student may face.

One and a half years after the course began, the results were encouraging, with over 100 students enrolled worldwide. Interaction with students was maintained through weekly forums and the practical parts were covered through 1-week mini-fellowships offered only for Spanish ophthalmologists. However, it was found to be very time-consuming for academic staff.

2) The Cataract and Refractive Surgery (Theory) – Postgraduate diploma (PGDip), an online postgraduate course offered by Ulster University9 is over 2 years long. This programme has been designed in cooperation with the Royal College of Ophthalmologists’ standards and is the only endorsed RCOphth refractive surgery course that is completed entirely online in the UK. Through this platform, students are offered the chance to learn the latest highly advanced and revolutionary technologies in refractive corneal and lens-based surgeries.

3) Students undertaking a Master of Medicine (Cataract and Refractive Surgery) at the University of Sydney10 need to complete 48 credit points in order to obtain their degree. The course consists of 36 credit points of core units of study in addition to 12 credit points of research thesis.

Core units include studies in ophthalmic anatomy, ophthalmic optics, refractive surgery and practical refractive surgery. The online component of the course includes lectures from internationally recognised corneal and refractive surgeons and interactive online discussions with coordinators.

Students are also offered the opportunity to attend a week of hands-on training through workshops and wet labs at the Sydney Eye Hospital as well as undertaking placements in accredited refractive surgical centres.

4) The European Society of Cataract and Refractive Surgeons (ESCRS)11 provides over 30 hours of interactive, assessed and accredited e-learning content, including surgical videos, diagrams, animations and quizzes.
	Cataract surgery, refractive surgery and corneal surgery courses are available as follows:

A) Cataract surgery. There are seven courses, including phacodynamics, the techniques and technology used in phacoemulsification, postoperative refractive outcomes and the management of endophthalmitis.

B) Refractive surgery. These six courses include refractive surgery, biomechanics and optics of the cornea, preparing for and performing LASIK, approaches to treat presbyopia and surface ablation techniques.

C) Cornea. These six courses including corneal diseases and dystrophies, diagnostic methods and a range of surgical procedures.

There are other educational resources that do not end up providing professional certificates but contribute in major parts in scientific online resources. Examples include:
	1) Cyber Sight12, developed and delivered by international ophthalmology experts, offers free online courses in ophthalmology, as well as a library containing a lot of hot topics discussed through live webinars, lectures and quizzes on subjects including cataract, glaucoma, paediatric ophthalmology and uveitis.

In addition, with ‘cyber sight consult’ you can contact 150 international experts who are standing by to help anyone who needs second opinions. Certificates earned contribute to Continuing Medical Education/ Continuing Professional Development (CME/CPD) credits, and all of the courses are optimised for mobile devices.

2) Wills Eye Hospital13. The department of Continuing Medical Education provides more than 100 courses in all eye subspecialties throughout the year. On Friday mornings weekly during the Chiefs round, the residents at the hospital present at least two unknown cases on different topics to attending staff, and other interested colleagues can attend through live webinars.

These excellent courses can be accessed free of charge on the website portal Wills Eye Knowledge, which also offers updates for glaucoma surgery, anterior segment surgery, orbital surgery, cataract surgery and retinal surgery.

3) 15-20 Institute14. The 15-20 Institute is a medical hospital ophthalmology training platform in France which has more than 3,000 registered users and 35,000 connections to platforms both in the country and abroad.
	Meetings take place on Thursdays monthly, and are hosted by a different specialist each time who discusses various subjects in ophthalmology.

In 2018, ten courses were offered, including four sessions of live surgeries in the operating theatre. The institute also provides attendees with seminars and discussions as well as valid certificates that add more to their CME hours in cornea, cataract, glaucoma, surgical and medical retina, oculoplasty and neurophthalmology, and ophthalmic emergencies.

Although e-learning has many advantages, there is still scope for improving the experience for students willing to engage with it. For example, learning could be made to be more adaptive, with courses tailored more to each specific student according to his or her specific learning needs and capabilities.

In addition, learners’ interactions with each other could be enhanced, with greater collaboration helping to increase levels of satisfaction and knowledge for students. And the role of the teacher needs to be truly transformative, so that they do not just distribute content but really facilitate the learning process and take an active part in assessing attendees’ performance8.

Again, it is important to bear in mind that e-learning is not intended to replace traditional methods. The educational goal is to improve the quality of refractive surgery training worldwide because learning is a non-stop process.

We believe that research should be directed towards studying both the effectiveness and limitations of online courses in refractive surgery so that any drawbacks can be overcome as it continues to develop as a learning modality. However, we have to keep in mind that surgical skills are still the core of ophthalmology practice and should be always secured through hands-on training.


	PROFESSOR JORGE ALIO, MD
	E: jlalio@vissum.com
	Prof. Alio is based at Vissum Instituto OftalmolÃ³gico de Alicante, Universidad Miguel HernÃ¡ndez, Alicante, Spain.

DR ALMUTEZ GHARAIBEH, MD
	Dr Gharaibeh is Visiting Professor of Ophthalmology at The University of Jordan, Faculty of Medicine, Amman, Jordan, and works for Vissum Instituto OftalmolÃ³gico de Alicante, Universidad Miguel HernÃ¡ndez, Alicante, Spain.

DR AHMED KHADER, MD
	Dr Khader is an ophthalmologist at The University of Jordan Hospital, Amman, Jordan.

1. Kemp N, Grieve R. Face-to-face or face-to-screen? Undergraduates’ opinions and test performance in classroom vs. online learning. Front Psychol. 2014;5:1278. eCollection 2014.
	2. Edmond M, Neville F, Khalil HS. A comparison of teaching three common ear, nose, and throat conditions to medical students through video podcasts and written handouts: a pilot study. Adv Med Educ Pract. 2016;7:281-6.
	3. Holmberg B. The evolution, principles and practices of distance education. Studien und Berichte der Arbeitsstelle Fernstudienforschung der Carl von Ossietzky UniversitÃ¤t Oldenburg [ASF] (in German). 11. Bibliotheks-und Informationssystem der Universitat Oldenburg. (2005) p. 13. ISBN 3-8142-0933-8. Retrieved 2011-01-23.
	4. Rosenberg M. J. (2001). E-Learning: strategies for delivering knowledge in the digital age. New York, NY: McGraw-Hill Companies, Inc.
	5. Ruiz JG, Mintzer MJ, Leipzig RM. The impact of E-learning in medical education. Acad Med. 2006; 81(3):207-12. Review.
	6. Rosenberg MJ. E-Learning: strategies for delivering knowledge in the digital age. New York, NY, USA: McGraw-Hill Companies, Inc.2001.
	7. Cataractle, Refractive E-Learning Course. https://crstodayeurope.com/articles/2008-mar/0308_25-php/.
	8. https://www.umh.es/contenido/PAS/:tit_fpo_9466/datos_es.html.
	9. Cataract and Refractive Surgery (Theory) - PgDip. https://www.ulster.ac.uk/courses/course-finder/201718/cataract-and-refractive-surgery-theory-13548.
	10. Master of Medicine (Cataract and Refractive Surgery) https://sydney.edu.au/courses/courses/pc/master-of-medicine-cataract-and-refractive-surgery.html.
	11. https://elearning.escrs.org/.
	12. https://cybersight.org/online-learning/.
	13. http://www.willseyeonline.org.
	14. https://www.15-20-institute.fr/fr.

Online ophthalmic learning in anterior segment surgery

Caroline Richards, editor of Ophthalmology Times Europe®, interviews Dr Lamis Baydoun on how corneal transplantation has changed-and what has been learned-since the introduction of Descemet membrane endothelial keratoplasty (DMEK)

A high number of corneal diseases only affect the inner layers of the cornea, that is, the Descemet membrane (DM) and endothelium. Until a few years ago, full-thickness corneal transplants-or penetrating keratoplasty (PKP)-typically took place, irrespective of whether the disease affected one or all layers. However, surgeons can now replace just the diseased parts with corresponding layers from healthy donor tissue in posterior lamellar corneal transplantation procedures.

Dr Lamis Baydoun, former head of academy and corneal surgeon at the Netherlands Institute for Innovative Ocular Surgery (NIIOS) in Rotterdam, has been heavily involved in developments with posterior lamellar keratoplasty and the most recent type of corneal surgery to spring from this, Descemet membrane endothelial keratoplasty (DMEK). At NIIOS, she taught dozens of surgeons across the world how to perform DMEK surgery, and her research continues to push the field forward.

Gerrit Melles is the founder of NIIOS and is regarded the ‘Pope’ of lamellar endothelial surgery. For 100 years, corneal surgeons performed only full-thickness penetrating keratoplasty-there was no other option to treat patients who have only one diseased layer. 

The results of Dr Melles’ experiments and his first surgeries opened up the field of endothelial keratoplasty. This started with deep lamellar endothelial keratoplasty (DLEK), then Descemet stripping (automated) endothelial keratoplasty (DSEK/DSAEK) and, finally, DMEK, the latest and most precise innovation, where you can practically restore the normal corneal anatomy.

HOW HAVE OPHTHALMOLOGISTS’ PERCEPTIONS OF DMEK CHANGED OVER TIME?

Many corneal surgeons were reluctant to adopt it at first. They were very uncomfortable with the technique and the graft itself, and perceived several obstacles.

Firstly, it was very difficult to recover the DMEK graft from a donor cornea. Secondly, the possibility of the graft unfolding during surgery incited fear in learning this technique because every time the delicate graft is touched, the corneal endothelial cells that are required to clear the cornea may be damaged.

The management of a new post-operative complication such as graft detachment (i.e., separation of the DMEK graft from the posterior stroma) was another concern. Patients faced complications that just did not occur with full-thickness penetrating keratoplasty (PKP) transplants, so surgeons felt they were far more comfortable remaining with the older technique.

However, over the longer term, the benefits of DMEK over all previous keratoplasty techniques were so overwhelming that the method could not be ignored any more-you could actually reach a level of visual outcomes that were comparable to those seen following lens or even refractive surgery! We had some very happy patients following the procedures. And when the patient is happy, of course, us doctors are also very happy.

WHAT ARE THE CHALLENGES FOR OPHTHALMOLOGISTS WHO ARE NEW TO THE PROCEDURE?

It is worth mentioning that the technique is now becoming much easier to master. Dr Melles first performed the surgery in 2006, so we have 13 years of experience to draw on, and during this time period we developed a standardised procedure and learnt how to handle the graft and complications better.

However, it is, of course, a challenge for surgeons starting out with performing DMEK. This is why courses are offered in Rotterdam: to teach surgeons tips and tricks, and help them to get over common obstacles, thus enabling them to adapt to DMEK surgery more quickly.

The main issue beginner surgeons have is knowing which graft side is the right side up. This is a key step for a successful surgery, and certain intraoperative signs can help indicate the correct graft orientation.

An intraoperative OCT (iOCT) may be a useful tool during the DMEK learning curve to visualise graft orientation and positioning. Once the surgeons are familiar with the technique and the surgical set-up, they do not necessarily need to use it, although it may remain a helpful tool in eyes with very, very edematous corneas.

WHICH DISEASES ARE BEST TREATED WITH DMEK?

The answer to this is: all diseases that concern the corneal endothelium. So, the cornea normally consists of five layers. Going from the outside to inside, you have: the epithelium; the Bowman layer; the stroma; the Descemet membrane; and finally the endothelium-and these final two layers are replaced in endothelial diseases.

There is one disease-Fuchs endothelial corneal dystrophy-which is very common and effectively treated with DMEK, showing outstanding results. Then there is bullous keratopathy, which usually occurs when corneal endothelial cells are damaged during certain eye operations; for example, during surgery to treat glaucoma or remove cataracts. This is another disease that is well treated with DMEK.

WHAT SHOULD PATIENTS EXPECT WHEN THEY ARE TOLD THEY NEED LAMELLAR CORNEAL SURGERY SUCH AS DMEK?

Patients can expect a minimally invasive treatment. Rather than excising the whole cornea and having the eye open during surgery, the surgeon will make only minimal, small incisions, entering  the eye with small instruments to remove the diseased layers before inserting a healthy donor graft.

Following this, the surgeon unfolds the graft before attaching it with an air bubble to the posterior stroma of the patient. This was actually how this surgery became so successful: previously, the graft was attached with sutures. These sutures can irritate the eye and induce inflammation, leading to possible transplant rejection.

Attaching the graft with an air bubble eliminates this problem, providing patients with a less traumatic surgery, and, after that, faster rehabilitation with better visual outcomes. From our experience at NIIOS, the graft can detach in about 10% of cases; however, not all cases may need a re-bubbling procedure. In my experience, graft detachment has become a controlled complication.

WHAT LESSONS HAVE YOU LEARNT SINCE THE FIRST PROCEDURE WAS PERFORMED?

What I have learnt is to no longer be afraid of the graft! This is something that at first is quite frightening. You are afraid of touching the graft and fearful because it behaves how it wants to behave. However, with experience, you realise that you can tell it what to do, and in most of the cases it will do what you want.

I have also learnt that not every surgery that is difficult necessarily ends up producing a bad result (it is often the other way around)-it can be surprisingly good even though it was a difficult surgery. These are mysteries that we still need to understand.

WHAT ARE THE BENEFITS OF QUARTER-DMEK SURGERIES?

Quarter-DMEK surgery was invented at NIIOS and the first series was recently published. The surgery was offered to patients with central Fuchs dystrophy and not those with bullous keratopathy. The rationale for this is as follows.

Fuchs dystrophy is a disease that sometimes only causes central guttae with mild or localised corneal oedema, but still-functioning peripheral endothelial cells. So, in a similar way to how Dr Melles invented DMEK, to offer a selective treatment for the patient that only treats the diseased endothelium and DM, we took that thinking a step further. We asked: is standard DMEK, with its 9.0 mm descemetorhexis (i.e., removal of the DM and endothelium) and round 8.5–9.5 mm graft, really the most selective treatment for all forms of Fuchs dystrophy?

If you have a patient with Fuchs disease but only central guttae that cause visual disturbances such as stray lights during activities such as driving, it would seem sensible to remove just this small diseased central portion and provide the person with a small graft piece for quick visual rehabilitation while sustaining his/her own peripheral cells. This is the idea with quarter-DMEK; you can use endothelial donor tissue more efficiently, hence instead of one standard graft, you can recover four quarter DMEK grafts from one donor cornea.

Endothelial keratoplasty brought us new understandings in cell biology and physiology. Further innovations are possible because of how the endothelial cells react and how they migrate after DMEK surgery. It is not just simply a case of placing some graft tissue in the eye: much more than this takes place.

WILL YOU BE ABLE TO USE PATIENTS’ OWN CELLS TO TREAT CERTAIN DISEASES IN THE FUTURE?

Potentially, yes. A lot is happening in this field at the moment. For example, in ‘Descemet stripping only’ or ‘Descemet stripping without endothelial keratoplasty’ for Fuchs disease, foreign tissue is not used, so there is no transplant. As a consequence, there is no risk of tissue rejection and so you avoid the problem of repeated transplants.

In this procedure, surgeons remove the DM and the endothelial layer in the centre of the cornea, which allows the cells from the periphery to migrate inwards to the centre and clear up the cornea. However, we still don’t know which cases should be treated without a transplant (and still profit from this treatment with fast visual recovery), so we currently feel that if we transplant a smaller quarter DMEK graft just in the centre of the optical axis and use it for these kinds of patients, then we will have combined the benefits of the migration approach, use less graft tissue with the chance of further reduction of rejection, and still give the patient fast visual rehabilitation.

In addition, a lot of research is being carried out on approaches with cell injections and cell carriers. I think we will still be doing some DMEKs for a couple of years, but it is likely such innovations will shake up the field again.


	DR LAMIS BAYDOUN, MD
	E: lamisbaydoun@hotmail.com
	Dr Baydoun is a consultant ophthalmic surgeon at the ELZA Institute, Zurich/Dietikon, Switzerland and at the Department of Ophthalmology at the University Hospital Muenster, Germany.

Being the ‘boss’ of the graft

Keeping a step ahead of the disease: proactive treatment for nAMD

This article was reviewed by Joseph F. Panarelli, MD

, the leading cause of irreversible blindness in the United States, is caused by ocular hypertension, which damages the optic nerve and results in visual field loss.
	
	There is no cure, but the disease can be managed with pharmacologic therapies, among other more invasive treatments, that lower and stabilize intraocular pressure (IOP).

Joseph F. Panarelli, MD, associate professor in the Department of Ophthalmology at NYU Langone Medical Center, New York, and Sahar Bedrood, MD, PhD, a glaucoma specialist at Acuity Eye Group, and assistant professor of clinical ophthalmology at the USC Roski Eye Institute, Los Angeles, recently spoke on the current state and future of glaucoma therapy and how compliance may not be an issue in the coming years. 
	
	

Recently approved therapies to treat open-angle glaucoma 

IOP reduction is the only known modifiable risk factor for open-angle 

a. However, studies have shown that disease progression and blindness are still possible even in patients on maximum medical therapy.


	
	How IOP factors into visual field loss isn’t entirely clear. According to Dr. Bedrood, one theory-known as the stress/strain model-is that IOP strains the sclera and optic nerve, causing apoptosis and loss of retinal ganglion cells.
	
	Another theory-the vascular theory-is when the blood vessels in the optic nerve don’t get enough oxygen, which leads to apoptosis, nerve fiber layer loss, and, eventually, visual field loss.

 are alike, and progression rates vary from person to person. 
	
	

 Stent offers IOP stability more than three years after surgery 

“Some patients who have a very strong genetic component are going to progress very quickly, and some, not so much,” Dr. Bedrood said. 

Co-morbidities such as sleep apnea and IOP fluctuations are other risk factors for visual field progression and greater visual field loss in certain patients. 

The causes of IOP fluctuations are multifactorial and can be due to poor treatment compliance, genetics, and a decline in treatment effectiveness over time.

“After 10-plus years of treatment, some of those treatments that initially worked may not work as well,” Dr. Bedrood said. “Sometimes, patients respond really well in the beginning and then over a couple of months or years they don’t, and then they fluctuate their IOP.”

Over a decade, selective laser trabeculoplasty (SLT) will wear off, requiring patients to have a touchup or a second round of treatment. Patients may develop an allergy or intolerance to glaucoma drops as well. 

“Over a course of 10 years, a lot can change,” Dr. Bedrood said. “Their rate of progression can fluctuate. Their tolerance of drugs can fluctuate. Oftentimes after 10, 15, or 20 years, we’re looking at other modalities of treatment like surgery or something that can regulate their pressure a little bit better-other additional drugs, for instance.” 
	
	

Sustained release implant offers long-term IOP stability, preserved vision control 

Prostaglandin analogues-such as bimatoprost, latanoprost, tafluprost, and travoprost-are common first-line treatments for patients with newly diagnosed 

. They are non-invasive and can reduce IOP by 25% to 30% with once-daily dosing,

Just because they are the most common first-line treatment doesn’t mean they are the best. Clinical trials have shown that SLT is just as safe and effective as drops, with a 20% reduction in IOP that lasts for up to three years without the hassle of daily medication.

Predicting glaucoma progression: More than meets the eye 

However, patients are often uncomfortable with the idea of a procedure initially and underestimate the burden of daily medication. 

Dr. Panarelli believes the pros and cons of SLT versus daily drops is a conversation worth having with patients early on in the treatment process. 

“I think it’s worth having a discussion with them [regarding] whether they prefer to start topical therapy or whether they would like to proceed with laser trabeculoplasty, especially now with data from the LiGHT trial,” he said.

Regardless of the initial approach, certain patients will ultimately progress.  When it is necessary to advance treatment, these patients may need a more aggressive approach.

“It’s a big decision for me to add another medication,” he said, adding that if a second medication is necessary, his preference is to go straight to a fixed-combination agent for those he suspects are “rapid progressors.” 

When selecting a treatment approach, clinicians must consider patient preferences, cost, and other factors impacting compliance. For example, patients with advanced 

 may be taking six to 10 drops a day.
	
	

 Eye-opener: Sticking to glaucoma therapy regimens vital 


	
	Drops that contain preservatives may cause ocular surface disease such as dry eye, leading to patient discomfort and decline in quality of life. Drop burden and unwanted side effects all impact compliance rates. 

“A lot of us are trying to decrease the number of total drops and maybe even move toward some of the preservative-free agents for a lot of our patients,” Dr. Panarelli said. “I think the medication landscape is changing, but I think the biggest thing we have to keep in mind [is] cost and compliance with all of our patients. [We’re] trying to find the most effective medicine in the least number of bottles.”

For the first time in decades, two new classes of drugs have been introduced for the treatment of open-angle 

: latanoprostene bunod and netarsudil. The agents have different mechanisms of action and could be disease modifying. 

Netarsudil is a Rho-kinase inhibitor that targets the outflow pathway.

Rho kinase inhibitors: Filling a gap in glaucoma treatment 

Netarsudil is a drug for the treatment of 

. In the United States in 2017, the FDA approved a 0.02% ophthalmic solution for the lowering of elevated IOP in patients with open-angle glaucoma or ocular hypertension, targeting the trabecular meshwork directly. 

Netarsudil is unique in that “none of the other medicines out there on the market actually work at the level of the trabecular meshwork,” Dr. Panarelli said. “By inhibiting Rho-kinase, we’re able to relax some of the actin and myosin contractions. By relaxing those contractions, we’re able to enhance outflow through the physiologic outflow pathway.”

It has other mechanisms of action as well and has the potential to lower episcleral venous pressure (EVP). “[This is] something that we do not see with other medication classes,” Dr. Panarelli said. 
	
	

The Magnificent 7: How many glaucoma medications are too many?

Latanoprostene bunod is a new version of a prostaglandin that also has a nitric oxide donating moiety.

The exact mechanism of action is somewhat complex, according to Dr. Panarelli, but it’s believed to have a number of benefits including smooth muscle relaxation/enhanced outflow through the trabecular pathway as well as increased uveoscleral outflow.

Fixed-combination netarsudil/latanoprost is another new drug on the market, which was approved by the U.S. Food and Drug Administration in 2019.

 The once-daily drug also reduces IOP by enhancing aqueous outflow through both the trabecular and uveoscleral pathways. 

“What is unique about the netarsudil/latanoprost combination is this is really one of the first times we actually had a medicine go up against latanoprost alone,” Dr. Panarelli said. “Latanoprost is one of our bigger guns out there, so it is encouraging to see that we have these new medicines, and it’s nice to see data that does support good efficacy with these different agents.”
	
	

Although clinical trial data support the efficacy of these agents, how exactly to use them in the real world and in whom are questions clinicians are currently wrestling with. 

“It’s nice to have some new medicines that are out there on the market because I think they all fit into our armamentarium somewhere,” Dr. Panarelli explained. “I think, as clinicians, we are still figuring out exactly how to use these medicines and how to mix them in with our other available agents.”

If a patient is not responding on a prostaglandin analogue, Dr. Panarelli will switch them from either latanoprost to latanoprostene bunod or from latanoprost to combination latanoprost/netarsudil. He also believes there is a place for the medications in patients with low-tension glaucoma, who are traditionally some of the most difficult patients to treat.

Dr. Panarelli has found netarsudil to be particularly useful in these patients because it lowers EVP. 

“Some of my patients can get down to that single-digit range, which is a number I often cannot get with traditional carbonic anhydrase inhibitors, or alpha-2 agonists, or even beta blockers,” he said.
	
	

There are some situations in which Dr. Panarelli will use netarsudil as a first-line agent. 

For example, if a patient is uncomfortable with the potential side effects of increased iris pigmentation and periorbital fat atrophy that come with a prostaglandin analogue, he may recommend netarsudil. 

He may also recommend netarsudil if the patient is already on an oral beta blocker or is hesitant to start on a beta blocker generally. 

“I have had several patients where I  have talked about having surgery,” he said. “We started netarsudil, and it’s actually been great in that they have gotten to their target IOP without me having to perform a trabeculectomy, which is huge for my patients.”
	
	

Researchers find long-term statin use linked to lower POAG risk

are not yet approved but currently in development. For example, bimatoprost sustained release (bimatoprost SR) is a first-in-class, sustained-release, investigational, biodegradable implant for the treatment of open-angle glaucoma. 

If approved, Dr. Panarelli said he believes bimatoprost SR could be “a game-changer” in that it completely takes patient compliance out of the equation and significantly reduces the overall treatment burden glaucoma patients face.

With bimatoprost SR, “all we ask [patients] to do is to come once every several months to get their treatment,” Dr. Panarelli said. “This can have a meaningful impact for our patients. It is one thing to talk to a patient and tell them that they are going to have an injection once every four to six months for the rest of their lives, but if we can give a patient a loading dose of a medicine and not need to reinject them from anywhere from one to (maybe) three years, that will resonate well.”
	
	

Defining alternative therapies for glaucoma

The big unknown with the implant is safety. Will there be any complications or adverse effects from an injectable form of medicine delivered into the eye every six months?
	
	Although data are limited to abstracts presented during conferences such as the Academy of Ophthalmology and American Glaucoma Society, Dr. Panarelli considers the safety and efficacy of bimatoprost SR to be positive so far.

“We have questions regarding issues with the cornea, and we have concerns about infection,” Dr. Panarelli said. “One of the things that has impressed me most is the fact that a lot of patients (up to 80%) who receive three doses over the first year did not need to be rescued over the next year that they were followed.”

Initially, Dr. Panarelli sees a place for bimatoprost SR as a second-line treatment when a patient is progressing or not achieving the IOP reduction needed on a prostaglandin or after SLT.
	
	

Greater IOP-lowering potential with iStent inject


	
	Once clinicians become more comfortable with the injection and have less concerns about the safety profile, clinicians may start with the injection rather than topical therapy. 

“If we can show very good safety profiles for these medicines, I think we are going to see a lot of physicians using this treatment early in their treatment algorithm,” he said. 

One of the primary issues in glaucoma is patient compliance. Up to 60% of glaucoma patients are non-compliant with daily drops.

 The reasons for this are multifold.
	
	First,

patients are generally older (people over age 60 are at increased risk for the disease). Second, glaucoma is a life-long disease. Patients may tire of daily drops and may struggle with opening the bottle or even getting the drops in the eye correct as they age. 

“They physically have to open up the bottles and place it in their eyes every single day,” Dr. Bedrood said. “That act is very different than taking a pill, and it is oftentimes more difficult for patients.”

Cost is a frequent issue as well, as eye drops are often more expensive than generic medications for other conditions. To address this, Dr. Bedrood suggests providing patients with coupons and enrolling them onto special programs where they can get lower prices. 
	
	

Reimbursement remains a hurdle for teleglaucoma

 is also asymptomatic, causing patients to be less aware of their disease. 

“[Patients] think, ‘Oh, I am fine. I am not feeling anything, I am not seeing any differently, and I will skip my dose today,’” Dr. Bedrood pointed out.

Dr. Panarelli said ophthalmologists  talk about glaucoma being a silent thief. However, it can be an issue for patients. 

“That is a big problem for our patients,” he explained. “They don’t physically see the need often to come to these appointments, or they don’t see the need to take their drops quite like some other conditions that are possibly affecting them.”

Dr. Bedrood stresses the importance of having frank conversations with patients on the importance of compliance, and if compliance remains an issue telling them pointblank they could face surgery.

She recommends asking how they’re doing on the medication and if they are able to open the cap. She even asks them to demonstrate how they are administering the drops into their eyes to ensure they have the proper technique. 

According to Drt. Bedrood, clinicians can also involve family members and/or caregivers to help as well. 

“If a family member is present, I usually like to ask them, ‘Who is giving the drop, and how often?’ It places kind of an onus of responsibility on whoever is in the room to help with this whole regimen,” she said.
	
	

Practical tips, pearls to help ease patients' financial burdens

If compliance issues on drops persist despite these strategies for improvement, the patient is left SLT or minimally invasive surgery. Clinicians must make this clear.

“I talk about surgery with patients because it perks their ears up and they say, ‘Oh, wait, I do not want surgery,’” Dr. Bedrood said. “And sometimes it reminds them that maybe it is better for them to use the drops.”

Despite these potential challenges, both physicians agree that, with all the new agents on the horizon, it is an exciting time in the field of glaucoma. 

“The sustained release, the implants, the ocular inserts, all of these things promise a way to deliver medications without having the patients do it,” Dr. Bedrood said. “Having it in a very sustained, steady way is a really exciting part of our future in

. I think that it will really help our patients in the long-term.”
	
	

Dr. Panarelli has no financial disclosures related to this content.

Pharmacologic treatment an option for open-angle glaucoma

Clinicians may soon be able to use genetic information alone to determine the risk of myopia in very young children, researchers believe.

“A personalised medicine approach to detecting children at risk of myopia is now feasible, although currently the accuracy of [polygenic risk scores] is not yet good enough to warrant their use in clinical practice,” wrote Neema Ghorbani Mojarrad and colleagues at the University of Bradford in Bradford, UK. They published their findings in JAMA Ophthalmology.

At present, the best predictor of the risk of myopia in children is a low hyperopic refractive error at an age before myopia typically manifests, so clinicians seeking to evaluate the risk in young children typically rely on a screening regimen of cycloplegic autorefraction. Successfully predicting the likelihood of children developing myopia can help clinicians recommend lifestyle changes such as spending more time outdoors, which can help mitigate or prevent the development of the refractive error.

However, the use of cycloplegic autorefraction is time and resource-intensive, so Mr Mojarrad and his team wanted to see if they could develop a polygenic risk score (PRS) for evaluating risk based purely on genetic information. To develop their PRS, the researchers conducted three genome-wide association studies (GWASs). Data used for the GWASs included 287,448 UK Biobank participants who had not undergone autorefraction, and 95,619 who had undergone noncycloplegic autorefraction.

In addition, researchers collected data on 328,917 individuals whose information had originally been compiled to study the relationship between genes and years of educational attainment, and had been downloaded from the Social Science Genetic Association Consortium (SSGAC) website. They then combined their data in a meta-analysis in order to increase the effective sample size, before generating a PRS for each participant using genotypes for 1.1 million variants.

The investigators validated their PRS by using it to predict rates of myopia in 1,516 women whose genome data and known rates of myopia were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC).
	The PRS derived from the SSGAC GWAS provided limited predictive accuracy (R2 = 0.14%, where R2 = 100% would be a completely accurate prediction). The autorefraction and non-autorefraction GWASs were also relatively inaccurate (R2 = 7.1% versus R2 = 6.9%).

The researchers were able to improve the accuracy of the PRS by combining sets of traits. The best result came from combining the autorefraction and non-autorefraction GWASs (R2 = 10.8%). Combining all three traits yielded even greater accuracy (R2 = 11.2%).

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