Ophthalmic challenges in 2022: Automation developments, pandemic backlogs and regulatory issues expected

Ophthalmology Times Europe, Ophthalmology Times Europe December 2021, Volume 17, Issue 10

Four members of the Ophthalmology Times Europe® Editorial Advisory Board consider the challenges and opportunities that lie ahead in Europe in 2022.

As 2021 draws to a close, members of the Ophthalmology Times Europe® Editorial Advisory Board share their perspectives and predictions on new developments and challenges that will affect ophthalmology next year. Themes include a focus on cost-effectiveness and value for money alongside automation, regulatory concerns and climate change. Public policy is top of Board members’ minds as the COVID pandemic progresses, whilst refractive disorders and ocular surface disease remain at the forefront.

Refractive issues

Prof. Peto: One of the most common causes of visual loss is presbyopia and this causes loss of income for many as the population ages. There should not be anyone lacking appropriate pairs of reading glasses in Europe and yet this is still a major issue. There is a big divide between Western and Eastern Europe and equity of access to basic services, such as a pair of glasses, should be the norm.

Prof. Alió: Despite the progress made with IOLs and laser procedures, presbyopia solutions still need to be better developed. An initial presbyope is not the same as a fully developed one and different treatments should be provided at different stages of the condition. This staging should probably be: pharmatherapy for the initial-intermediate presbyope, laser for intermediate cases and IOLs for advanced forms.

However, evidence to support each of the stages is lacking. PresbyLASIK is a technique that is not practiced by many but is very successful when properly indicated. IOLs are probably over-indicated today, sometimes being used in patients who are too young, and pharma-therapy does not yet exist.

Related to the previous point, accommodative lenses, rather than multifocal or extended depth-of-field (EDOF) lenses, should be the solution for pseudophakic presbyopia. The restoration of real accommodation is the physiological way to solve the issue but is still not properly accomplished.

Many unsuccessful attempts have been based on incorrect assumptions. The bag is probably not the best location to place a lens because the natural mechanism of fibrosis will probably cancel its effect. Sulcus implantation has been successful and is still under investigation.

Other mechanisms such as electronically-induced accommodation or refractive exchanges induced by pupil motility are a likely solution. 2022 should contribute to the further development of accommodative IOLs.

Dr Fazio: The debate continues as to which kind of presbyopia-correcting strategy is best overall or, at least, how to personalise the approach. Currently, there are seven types of advanced-technology IOLs available for the purpose: advanced monofocal; EDOF refractive; EDOF diffractive; sector bifocal; diffractive bifocal; trifocal; and extended near diffractive.

‘Minimonofocality’ could be added to the lens choice strategy to maximise the compensation of presbyopia. Studies comparing IOL types and strategies to ascertain their relative power and drawbacks are still lacking but remain urgent, for medico-legal reasons among others.

Prof. Peto: Myopia is the upcoming generation’s issue; more young people have it than we have seen in the current middle-aged/ elderly population. It is a hidden disability, and the full economic impact will only be felt when this generation grows up. There might still be time to act, by encouraging young people to spend more time away from the screen and providing appropriate lighting in schools, and this process really should start imminently.

Prof. Alió: SMILE is my favourite technique for myopia and should soon be available for hyperopia. However, despite its great biomechanical advantages, much less invasive surgery and good outcomes, the procedure still lacks the customised profiles, multifocal profiles in the creation of the lenticle, customised Q values and many other advantages of excimer lasers.

Intrastromal lenticular corneal tissue implants, now available from several companies, should be promoted as they are clearly going to replace excimer lasers because of their lower maintenance costs, lack of duplicate technology for the same purpose (i.e., excimer plus Femto) and faster, less-invasive surgery. Full development of SMILE will create a different environment for refractive surgery and will probably expand its indications to higher levels of myopia and hyperopia.

Dr Fazio: SMILE vs PRK vs LASIK vs phakic lenses: given a normal eye, with adequate corneal thickness and anterior chamber depth, and with −6 D myopia and 3 D cylinder, which technique would be the winner? Possible early and late complications, recovery time, precision and quality of vision all differ between the various strategies.

SMILE is the newest and most rapidly advancing strategy. It is more expensive for the patient, though, and the physician, already equipped with the old and trusted femtosecond + excimer LASIK suite, needs to purchase new technology. Papers have been published that apparently demonstrate the non-inferiority of SMILE to LASIK, and at a lower price, in terms of weakened biomechanics of the cornea. How this will translate to clinical advantage is, as of yet, unknown.

Cataract surgery

Prof. Alió: Capsulorhexis is one of the most important steps in cataract surgery. If it fails or is performed wrongly, it makes the patient a candidate for intraoperative complications or may negatively influence the performance of premium IOLs. Automatic capsulorhexis is a dream that will probably be accomplished in 2022.

The elegance of the femtosecond laser is counterbalanced by its high cost: cost-effectiveness has been demonstrated to be poor for this technique. Other procedures such as Zepto and especially Capsulaser (not diode laser capsulotomy) are cost-effective, more readily available to the practical surgeon, cheaper and need less complicated logistics.

The fast development of automatic capsulorhexis will be of immense value for the practice of cataract surgery, especially for non-high-volume surgeons, and will facilitate cataract surgery in terms of precision, reproducibility, better IOL placement and better quality of surgery in general.

Dr Fazio: After a season of keen interest during which it seemed to be the only future of cataract surgery, laser-assisted phacoemulsification (FLACS) stopped being fashionable. Why, when the technique is beautiful and safe? Simply because, given the current IOL and phaco needle technology, clinical results are not sufficiently different from those of the standard phacoemulsification technique.

We are waiting for a complete set of new lenses capable of being inserted through an opening of less than 2 mm and phaco machines adapted to FLACS and capable of carrying out surgery through the same width of incision.

Glaucoma

Dr Fazio: Minimally invasive surgery in the form of small ab interno shunts could become the first line of treatment for the insidious disease glaucoma. Quality of life, absence of local and general side effects from medical therapy, a lower economical burden for both the patient and the government, and overall better maintenance of the visual field are among the advantages of offering this kind of surgery earlier than the current protocol.

Artificial intelligence

Prof. Hafezi: The use of artificial intelligence (AI) in diagnostic equipment is the future of modern medicine. Although medical professionals cannot be replaced, AI-driven diagnostics will support and enhance the level of care provided to patients. These future devices will be able to detect irregular corneas, for example, at a much earlier stage than we see today.

The challenge that I see is to develop a way to capture ‘Big Data’ in a systematic way, to enable the machine-learning devices to process data. Aside from publication politics and commercial interest, it is of great value to access large amounts of similar data because there are intricate ways to analyse and utilise such data sets, developing a model to support AI development in the field of ophthalmology.

Eliminating the subjective approach with which doctors use current corneal diagnostic equipment and simplifying initial screening devices to capture basic images is essential to pave the way for AI-powered devices. Also, making screening devices affordable and easy to use increases the chances that more people use the same technology. The quality of the data would remain high because of the simplistic yet sophisticated approach.

So, the challenge is not only the development of screening devices but also their rate of adoption. Because the screening device is intended to be low cost, the profit margin will be small and, therefore, finding industrial partners who are willing to invest will be a major challenge.

Ocular surface diseases

Prof. Alió: Even though it has been attempted only recently, corneal stromal regeneration has been successfully reported as feasible and extremely promising for the treatment of corneal dystrophies: results of the first clinical study were published in the American Journal of Ophthalmology, Cornea, IOVS and Experimental Eye Research. The combination of stem cells with acellular corneal tissue raises a new possibility for keratoconus, opacified stroma and other corneal diseases.

The same is happening with the corneal surface: clinical studies have demonstrated the possibility of using mesenchymal stem cells (the same ones as for the stroma) to reconstruct the ocular surface in a much better and cheaper way than using mucosal epithelium expanded cells.

Corneal endothelial regeneration is still only in its initial phases but the Japanese studies are promising. We hope that 2022 will be a year that sees all these projects progress and make impressive accomplishments.

Prof. Hafezi: Prior to the 2000s, there was little-to-no mention of keratoconus in the literature. Fortunately, diagnostics have made significant advancements since then in terms of sensitivity, and irregular corneas can now be detected at a much earlier stage.

Fast-forward two decades and you can see a number of prevalence studies claiming that keratoconus cannot be considered a rare disease. However, the game has not yet been won.

The challenge is that keratoconus has not yet been adopted as a public policy initiative. Every child should be screened, especially in regions with a high prevalence. Specifically, every child should have the right to be screened by qualified individuals using high-quality screening devices.

This initiative can only be realised if patients, patient organisations, medical professionals, industrial partners and governmental officials work together to increase awareness about the disease and propose feasible solutions for how best to screen school-aged children regardless of financial limitations.

Dr Fazio: I am convinced that we are overtreating some of our keratoconus patients with corneal cross-linking and undertreating others. Corneal cross-linking is a rude technique. We damage keratocytes, inducing opacities and long-term flattening effects in an unpredictable way.

In some cases, it seems the cornea continues to develop keratoconus despite treatment. We need ways to better titrate depth and amount of treatment and to personalise the amount of cross-linked corneal tissue.

Prof. Hafezi: Anyone who has performed corneal cross-linking is aware that removal of the epithelium comes with several disadvantages and an increased risk for infection. The removal of the epithelium has been necessary until now to allow, firstly, enough riboflavin to penetrate the stroma and, and secondly, sufficient oxygen concentration in the stroma to maintain the cross-linking reaction.

One of the oldest ways for riboflavin to effectively penetrate an intact epithelium is through iontophoresis. Although effective, iontophoresis is complicated, increases the time and costs of treatment, and is rather uncomfortable for both the surgeon and patient. For these reasons, few surgeons have adopted this mode of treatment.

Recent developments have shown that sufficient riboflavin concentration can be achieved using penetration enhancers. Oxygen goggles have been developed that allow a steady stream of oxygen during the cross-linking procedure. Although this method is effective, this additional device presents challenges: a raised level of complexity, the bulkiness of the equipment, and increased costs related to the goggles and required oxygen.

The challenge that I am facing is to find a safe and effective treatment protocol that can be adopted by medical professionals everywhere with little investment and a flat learning curve. Additional devices and complicated procedures limit the number of medical professionals who can provide the treatment. Access to treatment is imperative for patients, especially in regions with proven high prevalence.

Furthermore, if the treatment protocol is simple, patient risk decreases. So, a challenge I have is providing a means to enable an epi-on approach that is affordable, simple, safe and effective; without additional oxygen and without iontophoresis; ideally performed in an office-based manner.

Regulatory issues and antibiotics resistance

Prof. Hafezi: There is confusion amongst colleagues regarding the use of the term ‘off-label,’ which applies to medical devices or pharmaceutical drugs that have been approved for clinical use in one indication but are used for another. An excellent example would be the off-label use of the intravitreal injection bevacizumab (Avastin, Genentech/ Roche). The drug has not been approved for age-related macular degeneration (AMD) but is registered for the treatment of colon carcinoma. Off-label use is generally legal.

However, use of non-CE-marked riboflavin is an example of something that does not constitute off-label usage. Several companies in the EU sell riboflavin solution that is not CE-marked and the use of such riboflavin is unlawful in any European clinic. What many surgeons do not realise is that they are forgoing their liability insurance when they use this low-grade, non-conforming formulation.

Even riboflavin pending a CE-mark is in clear violation. The purpose of the CE-mark is that a notified body declares that the medical device has met the General Safety and Performance Regulations of all current European Medical Device Regulations. Anything considered pending is not approved.

Often, non-conforming companies sell their riboflavin solution directly to surgeons at congresses. The reason for direct sales is because these companies cannot legally ship their product without having it be confiscated at the borders for non-compliance of regulatory requirements.

Aside from the commercial implications, the real problem is patient safety. I see many cases, even in Switzerland, of surgeons using non-CE-marked riboflavin solution. All too often, the illegal use of low-grade riboflavin solution leads to medical complications (ineffective/ shallow treatment, central scars and even corneal melting). So, ask yourself: are the savings really worth the risk?

To check, ask the manufacturer or supplier to provide a Free Sales Certificate, sometimes called a Certificate for Export. This certificate is only provided when the product is legally sold and distributed in an open market.

Another huge challenge is the looming antibiotic resistance that the World Health Organization has been warning us about for years. The time is now to start developing medical treatment strategies to combat bacterial infections without the use of antimicrobials.

Peer-reviewed publications on PACK-CXL, which stands for ‘photoactivated chromophore to treat keratitis-corneal cross-linking’, have grown exponentially in the past 5 years. Using PACK-CXL as an adjunct therapy along with antimicrobials to treat bacterial, fungal and mixed infections has been proven to be effective in shortening the time to healing and thus in reducing the number of follow-ups needed.

We have submitted for publication the results of our prospective multicentre study on the effect of PACK-CXL alone and have seen that in bacterial, fungal and mixed ulcers of up to 4 mm in diameter, a primary high-fluence PACK-CXL treatment is just as effective as antimicrobial therapy in terms of days to healing.

Coronavirus pandemic

Prof. Peto: The COVID pandemic-related challenges we are likely to see in 2022 will largely depend on where people live and on how a given country is pulling through the crisis. The world’s population has been affected by entirely new ways of living. The level of uncertainty has been high and many of our patients have not been seen in a timely manner.

Dealing with serious complications of delayed presentation is becoming more common and unfortunately people might lose their sight. Late presentation for AMD and diabetic retinopathy/ maculopathy is quite common and patients at risk are juggling several appointments alongside conflicting advice about whether they should stay at home or attend the clinic.

Providing low-vision care to those who have already lost sight is a challenge, since many of these patients have become even more isolated during the pandemic. An appropriate level of care used to involve face-to-face consultations, discussions on special needs and teaching of new skills for everyday living. Although video or telephone consultations allow some level of care to be provided, these do not suit everyone and many patients do not have access to this, leading to further deprivation and isolation.

Sustaining our services will remain a challenge as many countries struggle with a low number of ophthalmologists carrying a high burden; trying to see the rising number of patients; teach the next generation of ophthalmologists; keep up with research and education; and continue to thrive despite all the pandemic-related difficulties.

In addition, we will have to look at our services: where we are producing waste, whether we can reduce our footprint and how we can provide the best service to our patients. We cannot ignore our contribution to climate change any more but need to think about where our surgical waste goes and how we could use and re-use equipment better.

Jorge Alió is professor and chairman of ophthalmologyat the University Miguel Hernandez de Elche, Alicante, Spain.
Farhad Hafezi is chief medical officer at ELZA Institute AG, Dietikon, Switzerland.
Paolo Fazio runs a private practice specialised in laser and intraocular refractive surgery as well as glaucoma in Catania and Caltanissetta, Sicily, Italy.
Tunde Peto is professor of clinical ophthalmology at Queen’s University Belfast, Belfast, UK.