Ophthalmic challenges in 2021: What to expect in the coming year

2020 has been a strange year for healthcare and medicine, and many now look to 2021 with hope for better times ahead. As we leave the year behind, five members of the Ophthalmology Times Europe Editorial Advisory Board share their perspectives and predictions on new developments and challenges that will affect ophthalmology in the new year. Themes in the wake of the COVID-19 pandemic include cost savings and patient selection, alongside an interest in technology and digital applications, while concerns about refractive disorders, cataract surgery, glaucoma and retinal disease remain important.

Albert J. Augustin is professor and chair of the Department of Ophthalmology, Klinikum Karlsruhe, Karlsruhe, Germany.

Christophe Baudouin is professor of ophthalmology and chairman of the Quinze-Vingts National Ophthalmology Hospital, Paris, France.

Christoph Faschingeris clinical professor in ophthalmology and optometry and was formerly based at the University Eye Clinic of the Medical University of Graz, Austria.

Tunde Peto is professor of clinical ophthalmology at Queen’s University Belfast, Belfast, Northern Ireland.

David Spalton is a consultant ophthalmic surgeon at St Thomas’ Hospital, London, UK, and is honorary consultant to the Royal Hospital Chelsea (the Chelsea Pensioners) and King Edward VII’s Hospital for Officers, London.

Refractive issues

Prof. Augustin: Small-incision lenticule extraction (SMILE) is increasingly being preferred over conventional flap-based procedures for the treatment of refractive errors. The procedure involves different phases, such as docking, femtosecond laser application, lenticule dissection from the surrounding stroma and extraction. Various techniques have been described to simplify the process of lenticule extraction and minimise complications.

Many authors have nicely demonstrated that SMILE is comparable to femtosecond LASIK (FS-LASIK) in terms of safety, efficacy and predictability, showing advantages of better ocular surface stability and biomechanical strength compared with FS-LASIK. Nevertheless, I suggest that proper patient selection is crucial to achieve the best visual outcome. With increasing surgical experience within the next few years, a standard technique is expected to evolve that may be performed in all types of cases, with optimal outcomes and minimal adverse effects, making SMILE a leading procedure in refractive surgery worldwide.

Prof. Faschinger: Glasses for presbyopia should be offered at a reasonable price to all people, including in developing countries. Progressive lenses are the optimum choice for people who need them due to refractive problems in their distance vision.

Another refractive issue is high myopia: to try to prevent this from occurring, it is important to recognise myopic axial length early and treat with atropine eye drops, as well as ensuring children go outside and so are exposed to sunlight for at least 2 hours a day. In addition, if possible, special contact lenses can be used, for example, MiSight (Cooper Vision), MyoVision (Zeiss), Myopilux (Essilor) or MiyoSmart (Hoya); or glasses with a special design such as the Stellest lens (Essilor).

Another suggestion is adapting computer desktops so that bright text is read on a dark background. It is also important to disseminate information on the fact high myopia at a young age may lead to severe sight-threatening diseases of the eye, such as retinal detachment, myopic maculopathy or glaucoma.

Cataract surgery and IOLs

Prof. Spalton:Post COVID-19, the cost pressures on cataract surgery will be relentless. Immediate bilateral sequential cataract surgery (IBSCS) will become the treatment of choice. Studies show no difference in refractive outcome or complications compared with sequential surgery and there are advantages for the patient, the hospital and the financial provider. Careful patient selection, high-quality biometry and surgery, and operating theatre logistics are the keys to success, and studies show that IBSCS is appropriate for more than 70% of patients.

Monofocal IOLs with enhanced depth of focus such as Vivity (Alcon), Tecnis Eyhance (Johnson & Johnson Vision) and ME4 (Santen) will displace standard monofocal IOLs because they offer patients more spectacle independence with negligible dysphotopsia. The Carlevale IOL will become the implant of choice for sulcus fixation in the absence of capsular support. And, building on femtosecond laser, eye-tracking technology and three-dimensional imaging, we will start to see the beginnings of robotic cataract surgery.

Prof.Faschinger: High-quality cataract surgery in developing countries should be a focus: doctors should be supplied with good microscopes, modern biometry machines, proper surgical equipment and autoclaves, and IOLs in many dioptres (spherical and cylindrical). They should also be trained in phacoemulsification and small-incision extra-capsular cataract surgery techniques. These should be offered to the patients at a reasonable price and patients should be transported free-of-charge to surgical centres by social services.

Glaucoma

Prof. Augustin: Glaucoma therapy represents a tough challenge for general ophthalmologists and glaucoma experts alike. Despite the wide armamentarium of medical therapies currently available, it can be an arduous task to obtain the optimal target intraocular pressure (IOP) for each patient.

In recent years, I have implemented laser treatment in the management of glaucomatous patients, which has proved a safe alternative to other treatment modalities such as topical therapy. In addition, it has a favourable side effect profile.

Different types of laser treatment have been proposed. Among them, selective laser trabeculoplasty and laser transscleral cyclophotocoagulation have been shown to reduce IOP by increasing aqueous outflow and decreasing aqueous production, respectively.

In addition, a new subthreshold laser technique, micropulse transscleral cyclophotocoagulation (mTS-CPC), has been developed as a potential alternative to traditional laser procedures. The micropulse modality, which is characterised by off cycles, allows thermal dissipation and thus leads to less collateral damage such as tissue scarring. mTS-CPC deserves consideration as a first line choice of procedure for treating patients with primary open-angle glaucoma because of its outstanding effectiveness and limited side effects profile.

Prof: Faschinger Fifty percent of glaucoma patients are undiagnosed because there is a lack of education compared with diseases such as diabetes, hypertension, high cholesterol and several cancers. Also, there are fewer ‘goodies’ to incentivise preventative check-ups, such as discounts to insurance costs.

Education should start with regular spots or movies on TV and/or on smartphones. Lost retinal nerve fibres cannot be brought back again: it is impossible to buy, borrow or lease them, even for millionaires.

Unnecessary therapies should be avoided in eyes without any glaucomatous changes. IOP that is higher than statistically normal does not point only to glaucoma and is very rarely an indication for therapy. Establishment of an individual risk profile will save money and will avoid the possible side effects of therapy.

Imaging, monitoring and telemedicine

Prof. Augustin: Three-dimensionalvisualisation during vitreoretinal surgery is critical to achieve the best anatomical and functional outcomes, given the delicate and microscopic features of retinal structures. Many studies have shown that 3D imaging technology in vitreoretinal surgery is associated with improved ergonomics and enhanced surgical team communication and education, as well as with reduced retinal phototoxicity and increased depth of surgical field. In particular, physician questionnaire survey scores demonstrated a better depth of field at high magnification for the digital 3D system.

The next step, already reached, is represented by the integration of optical coherence tomography (OCT) into the digital visualisation system, which allows intraoperative display of OCT images on a 4K screen, facilitating the identification of subtle retinal alterations. In addition, the digital platform enables the simultaneous view of OCT and the surgical field. In my opinion, a step forward is necessary in order to allow a ‘real’ simultaneity between the retinal image, as seen by the surgeon under the microscope, and the corresponding OCT image.

Digital progress permeates all aspects of our lives and is becoming increasingly present in surgical departments such as the ophthalmologic operating room. It is only a matter of time before improved 3D visualisation systems are regularly used in most surgical settings.

Prof. Peto: Telemedicine and tele-ophthalmology have played prominent roles in ophthalmology for a while, but never more so than during the COVID-19 pandemic. During this time, healthcare providers and patients learnt to use software that enabled online communication and telemedicine triage. This resulted in many patients not having to attend face-to-face consultations.

In 2021, the challenge will be to test the safety of this approach and address the ‘missed’ cases when they eventually present. We must learn from these and then make the telemedicine approach even more widely available for those aspects of ophthalmology where it proves to be safe and sustainable.

Home monitoring for medical retinal diseases, such as age-related macular degeneration, has been steadily growing, but our understanding of how to roll this out safely is limited. In addition, many of the necessary devices are not widely available and there is not enough information about where they fit safely and sustainably into the current clinical pathways.

There is also not enough data on how the consultations resulting from these examinations will be managed, and in some countries, reimbursed. The challenge in the next year will be to incorporate more home-monitoring devices and techniques into clinical pathways in order to minimise unnecessary hospital visits while maintaining treatment opportunities for those who do need to attend.

Retinal disease, diabetic eye disease and gene therapy

Prof. Augustin: For a long time, there was no cure for people affected by inherited retinal diseases. However, in recent years, genome sequencing techniques have allowed us to discover new genes and pathogenetic mechanisms underlying such diseases. Thus, alongside diagnostic and prognostic tools, new therapeutic perspectives are emerging.

In particular, I would like to highlight the development of a new revolutionary gene-editing technique, the CRISP-Cas9 system. It has provided a fresh approach to gene therapy in every medical field, including ophthalmology. Trials in humans have already been conducted with very promising results for both X-linked and autosomal dominant forms of retinitis pigmentosa as well as Leber hereditary optic neuropathy, for which the first gene therapy product voretigene neparvovec (Luxturna) was recently approved.

The main challenge for the future will be the identification of optimal, less-invasive gene delivery systems. In this respect, I would like to stress the importance of an up-and-coming technique: sonoporation. In my opinion, this method might change the paradigm of inherited retinal disease management.

The sonoporation technique uses microbubbles of ultrasound contrast agents containing the relevant gene-editing system with the application of ultrasound to the region of interest in order to deliver gene therapy to specific organs. Hopefully we will soon be able to tell our patients suffering from inherited retinal diseases that we will be able to help them.

Prof. Peto Diabetes is an established risk factor for poor outcomes in patients with COVID-19; therefore, during the pandemic many patients have been asked to shield or self-isolate for extended periods of time. At the same time, many have required ophthalmic examination and treatment, and none of these can be completed using telemedicine.

Face-to-face consultations and treatment are time-consuming, increasing the risk of infection. Those patients requiring treatment were subjected to significant delays in accessing what they needed and some even progressed to sight loss. In 2021, all newly diagnosed diabetes patients in addition to those with delayed treatment will need to be seen and treated.

Ocular surface diseases

Prof. Baudouin We must develop a better recognition of the severity of dry-eye disease (DED): it is rarely sight-threatening but, besides having a major impact on quality of life, it also impairs quality of vision, resulting in unstable vision, ocular fatigue and difficulties in concentration and working on a computer. Efforts must therefore be made to help patients who are deeply and continuously suffering.

We also need a greater appreciation of the discrepancy between signs and symptoms of DED. Patients often complain of very severe symptoms but the clinician may lack the tools to understand the reasons for them. On the other hand, others experience such severe corneal damage that they do not suffer any more and develop neurotrophic keratopathies that link corneal defects to dry eye, acting together as a vicious cycle. Such cases may be due to chronic inflammation and lymphocyte activation, which is often difficult to identify clinically.

Confocal microscopy assessment of the cornea and new-generation OCT with higher resolution may be helpful but are not always available for clinicians. Other new technologies, such as meibography, tear film interferometry, aberrometry and topography, are becoming progressively more available but remain mostly limited to research centres.

Inflammation has been recognised as a major underlying mechanism of DED but we are unable at present to precisely identify inflammation levels, its mechanisms and severity. There are several types of inflammation present in the disease, which are mediated by Th1, Th2 or Th17 lymphocytes, B-cell autoantibodies or innate immunity, and complex interactions exist between the inflammatory cascades, mediators and cellular actors. Biomarkers, especially in point-of-care settings, would bring valuable information to target precisely the mechanisms of DED, in order to help damaged ocular surface tissues to recover and relieve patients of their disabling symptoms.

Neuropathic pain has emerged in recent years as an explanation for the significant symptoms that patients with mild or no visible clinical signs exhibit, or in cases of persistent symptoms despite improvement of the initial lesions, namely, corneal damage. The brain becomes chronically stimulated in a pain mode, which subsequently affects patients’ mood and leaves them at risk of depression. The chronic pain is very difficult to alleviate and may require specific pain-relieving strategies.

The pain may be explained by repeated or sustained stimulation of cold receptors of the corneal nerves. Confocal microscopy of the corneal nerves may sometimes recognise signs of chronic nerve activation, such as neuromas and inflammatory infiltrates. Targeting cold and/or noxious receptors of corneal nerves will certainly be another promising challenge of the next few years.

Customised or tailored therapies based on disease mechanisms will continue to be developed: most DED therapies remain based on corneal lubrication and tear substitution, which is not sufficient in severe cases. New immunomodulating strategies have been developed and have changed the paradigm from treating the consequence, i.e., dry eye, to targeting the causes(s), namely inflammation. Other agents could be developed to block more specific mechanisms, such as tumour necrosis factor, interferon or microbiota-associated cascades of mediators.

Prof. Augustin: The management of severe ocular surface diseases such as corneal ulcers and chemical injuries has changed dramatically over recent years. Amniotic membrane transplantation (AMT) is currently playing a fundamental role in the treatment of these disease entities.

This surgical procedure has proven to be a safe and effective alternative to traditional corneal transplantation, and has shown to be able to reduce intraoperative complications and improve visual acuity. The beneficial effects result from the amniotic membrane’s anti-inflammatory and anti-fibrotic properties. In addition, AMT contains growth factors that promote epithelial wound healing on the ocular surface.

In our clinic, we are improving the use of AMT for corneal and conjunctival reconstruction in many clinical situations, including acute chemical burns, persisting corneal ulceration of varying aetiologies and in cases of conjunctival scarring, such as for conjunctival neoplasia and pterygium surgery. Thus, AMT can be considered a major breakthrough in reconstructive eye surgery, providing us with the possibility of treating chronic surface diseases with a high safety and efficacy profile, and thereby minimising surgical time and intraoperative risks.

Patient communication and research

Prof. Faschinger: ‘Gadgets’ are worth mentioning as we look to 2021: ophthalmologists should remain alert in avoiding all surgeries that can be considered strange and unnecessary, such as changing the colour of the iris by implants. This type of surgery amounts to complete nonsense and destroys the eyes. Even if people are prepared to pay a large amount of money, all seriously thinking and acting doctors should say “no” to conducting such surgeries.

Prof. Peto: Working relationships between patients and healthcare professionals and amongst clinical teams changed beyond recognition in 2020: keeping a distance away from each other, wearing masks and not seeing our patients as frequently as planned had profound effects on how we communicate. Adding these aspects to the fact that many medical retina patients are either elderly, have significant comorbidities or have visual and/or hearing loss (of a combination of all of the above), giving information and displaying empathy using well-understood facial expressions has to be re-evaluated.

In 2021, the challenge will be to re-establish relationships, making sure that patient information is up to date and is understandable by all, even to those who do not use online resources, and making sure nobody is left behind without access to treatment. Research is crucial for treatment provision: it is well established that those ophthalmology units that have an active research profile have better outcomes in treating patients in their clinics.

The rigorous thinking process required for conducting good-quality research and the necessity of keeping up to date with the relevant topics have a long-lasting impact on how we treat our non-research clinical patients as well. Many clinicians also play a role in basic science and/or translational research and these have long-term effects on treatments offered in the future.

The challenge at our clinic will be to rebuild research portfolios and programmes that have been stopped because of the pandemic, refocus our research intentions on those fields that emerged as important, and re-evaluate how we involve our patients in framing our questions and research priorities.

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Albert J. Augustin
E: albertjaugustin@googlemail.com
Prof. Augustin declares that he recieves advisor and speakers honoraria with Allergan and Alimera.

Christophe Baudouin
E: cbaudouin@15-20.fr
Prof. Baudouin declares interests with Aerie, Alcon, Allergan, Horus Pharma, Santen and Thea.

Christoph Faschinger
E: christoph.faschinger@medunigraz.at
Prof. Faschinger declares no financial interests.

Tunde Peto
E: T.Peto@qub.ac.uk
Prof. Peto declares no financial interests.

David Spalton
E: profspalton@gmail.com
Prof. Spalton is a consultant to Optical Express, AnewOptic Inc., AVS/Santen and Keensight.