The World Health Organisation (WHO) announced a new flagship initiative, “a mental health coalition to support system reforms and COVID-19 recovery” in Europe.

This was undertaken because of the organisation’s recognition that “mental health is a key public health concern in the WHO European Region – more than 110 million people are living with some kind of mental health condition, accounting for over 10% of the population.”

“The mental health flagship will bring together a broad coalition of mental health leaders, champions, service users and other partners to improve mental health policies and practices across the region,” the WHO said in a statement.

Considering the COVID-19 virus, focusing on mental health now is especially important given that the measures to prevent the virus from spreading, such as social distancing and quarantining, in addition to the dangerous working conditions for health care workers, are having a psychological impact on the population and exacerbate pre-existing anxiety.

The WHO explained that the Mental Health Initiative will challenge “stigma and discrimination by improving mental health awareness and literacy among not only the public but also service providers and decision makers.”

In addition, it will enhance access to “person-centered, rights-based mental health care in communities. This will expedite progress towards universal health coverage for people with mental health conditions and make the case for a parity of esteem between mental and physical health.”

The Mental Health initiative is one of 4 launched by the WHO. The other 3 priorities for WHO/Europe over the next 5 years are digital health and innovation, behavioural and cultural insights, and immunization.

Articles

Organisation is kicking off a flagship initiative as it views mental health as a key public health concern in the WHO European region, where more than 110 million people are living with some type of mental health issue. 

WHO initiative builds a coalition for system reforms, COVID-19 recovery in Europe

The coronavirus pandemic has triggered a seismic shift in the way ophthalmologists interact with their patients, forcing them to think on their feet and find ways to quickly adapt their workflows. However, as the crisis continues, it is becoming apparent that some of the changes they have had to make, such as increasingly opting for virtual consultations, could become more permanent, as evidence of their benefits to doctors and patients alike starts to mount. Arguably, the pandemic has paved the way for greater opportunities for positive change within ophthalmology and indeed, in healthcare in general.

I asked Prof. Mariya Moosajee, consultant ophthalmic surgeon and clinical academic ophthalmologist at Moorfields Eye Hospital, London, how her working life has changed and how those who specialise in providing services for genetic eye disorders can continue to provide the best care for their patients both during the pandemic and beyond.

Prof. Moosajee’s speciality is genetic eye disease, so the majority of her patients have been deemed non-urgent during the pandemic. A lot of such patients across the UK have seen their appointments cancelled, but Prof. Moosajee decided to consult all her patients virtually from the start of the crisis.

How have you had to adapt your workplace during the pandemic?

I have been able to work from home and consulted patients either by telephone or using ‘NHS attend anywhere,’ a secure web-based platform for patients with pre-arranged video consultation appointments, that was nationally funded by National Health Service (NHS) England and NHS Improvement to support NHS trusts and foundation trusts in their response to the COVID-19 outbreak.

I hold my clinics at the same time as they would have been held pre-COVID-19 and allocate patients to my team. I then meet with my colleagues at the end of every clinic on Microsoft Teams so that they can present each case.

We discuss the patients’ future management as a multidisciplinary team; we have a family support officer; a developmental paediatrician; a genetic counsellor; an extended role orthoptist; a low vision optometrist and a paediatric ophthalmology fellow. If we feel our patients need a low vision assessment or specific paediatric input (as a vast number of genetic eye disease patients have systemic features), then the relevant personnel will follow up the patient with a further phone call. It has worked really well; we have consulted 220 patients in total: 150 children and 70 adults with genetic eye disease.

We are restarting face-to-face clinics in the next month. At that stage we will have prioritised patients that will need to come in for clinical assessment and to give blood samples for genetic testing.

Adults who have had recent ophthalmology assessments locally or in other services at Moorfields can be sent blood packs which enables them to take their own blood without having to travel into London and send the sample back to us so we can process it for genetic testing. In fact, the whole process can be undertaken remotely.

What are your views on virtual consultations?

I have been pushing for virtual consultations in genetics for a long time. Prior to COVID-19 (last April–June 2019), we undertook a patient-reported survey with just over 100 paediatric or adult participants, who were either new or follow-up patients, to ascertain their views on virtual consultations and their acceptability.

We found that over 65% percent of participants prefer to have their investigations carried out locally, followed by a virtual consultation with specialists at Moorfields Eye Hospital for the review of these results. Adult participants favour video calls, with contact via the telephone being the least popular response.

The opposite is true for parents and guardians of children, who prefer contact via telephone over video call. There was no difference between the views of new or follow-up patients. Interestingly, despite most patients preferring virtual contact, the majority do not want to be seen virtually for every appointment until a treatment or trial becomes available.

What innovations do you think might be needed in the future?

I do not think we can go back to the way we were working. We can greatly increase our efficiency and patient experience by a combination of virtual and face-to-face consultations.

Patients do not want to wait for hours to have imaging and see a consultant, but they definitely want to see specialists who know about their rare genetic eye condition and who can assess the results of investigations undertaken locally, as well as inform them of the latest research and trials.

The long, detailed records we take in genetics on the onset and progression of symptoms, and prenatal, birth and family history can all be undertaken virtually. Genetic counselling is also a lengthy process that involves an unrushed conversation to ensure patient understanding of the complex topic of inheritance and genetic mutations, informed consent and family planning.

Studies in cardiac and oncogenetics in the Netherlands showed high levels of patient satisfaction for those receiving virtual genetic counselling. I would strongly recommend Telegenetics moving forwards.

In the UK, genomic medicine services are being introduced across all medical specialities, funding for genetic testing is becoming centralised and whole genome sequencing will soon be available to most patients on the NHS. We are trying to encourage more ophthalmologists around the country to order genetic tests for patients.

Moorfields Eye Hospital is also hoping to provide a virtual genomic service to ophthalmologists, to offer guidance and advice on how to manage genetic eye disease patients locally without the need to send them to tertiary referral centres unless necessary. I think this will be a huge step forward for patients who have previously not been able to access genetic services due to local funding restrictions.

I have also created an open access web-resource called Gene.Vision, which is an A-Z of genetic eye disease with two interfaces; one for healthcare professionals and the other for patients. The version for patients includes in-depth sections on how to cope with sight loss and associated aspects of daily life that can be affected, such as driving, education and employment.

The aim of the resource is to feature the signs; symptoms; genetic causes; patient management; referral needs; current information on research and trials for a disease/gene; and any support groups that would be beneficial for the patient, for each genetic eye disease. It has been tested by patients with sight loss with input from digital accessibility consultants, one of who is deaf-blind with Usher syndrome. It will be launched next month (www.gene.vision).

How can you best serve your patients during the pandemic?

Most genetic eye disease patients had their appointments cancelled during the lockdown. When you are forced into isolation, it can cause some individuals to focus more strongly on their own health and well-being.

Calls to sight loss charity helplines increased but they had no expertise to answer the medical queries. So, I offered to undertake a voluntary weekly ‘Ask the expert session’ for Retina UK, Microphthalmia, Anophthalmia and Coloboma Support (MACS) charity and Aniridia Network.

I spoke to at least six patients per session and every caller had a valid reason to get in touch; issues raised included not getting access to expert services, deterioration in vision and interestingly, I received a number of calls from patients who were experiencing increased visual hallucinations as part of Charles Bonnet syndrome (CBS). Based on this anecdotal evidence, we undertook a survey of 45 elderly patients with sight loss due to CBS, with over 40% of them having macular-related disease.

Over 55% of patients reported increased frequency of visual hallucinations;

Approximately 50% had alterations in the nature of their hallucinations and emotional response in terms of more sinister hallucinations, with more associated fear and anxiety; and

Nearly 70% felt greater feelings of loneliness but 60% had not accessed support services.

It is clear from this that we must learn to stay connected with our patients, ensuring they do not feel isolated. Sending a letter of cancellation or discharge is not appropriate during these difficult times. A phone call by an eye clinic liaison officer or genetic counsellor can be very gratefully received by patients. Sight loss charities may be able help in this regard but, like many, they have been suffering from reduced income and furloughed staff. 

Prof. Mariya Moosajee, MBBS, BSc, PhD, FRCOphth

E:  m.moosajee@ucl.ac.uk
Professor Moosajee has no financial disclosures.

COVID-19: How one ophthalmologist is dealing with non-urgent cases 

Cedric Schweitzer, MD, is an ophthalmologist based at the University Hospital Bordeaux in France.

The femtosecond laser is widely used in ocular surgery, particularly in refractive surgery with LASIK flap creation or small incision lenticule extraction, as well as in corneal graft or corneal inlays for keratoconus. Owing to the very short pulse of the laser, the technology provides highly precise ocular tissue cuttings without causing collateral damage to surrounding structures.

The application of femtosecond laser to cataract surgery was the obvious next step of the technology and has led to femtosecond laser-assisted cataract surgery (FLACS) emerging as a recent breakthrough. However, it has required additional developments such as specific docking systems and real-time imaging to enable cuttings of the opacified crystalline lens to be made without distortion of ocular structures during the laser procedure. Safety zones to preserve surrounding structures within the eye also needed to be considered (Figure 1).

As expected, laser-created capsulotomy is more precise, circular and centred than manual capsulotomy. In addition, corneal incisions have more reproducible squared-edge architecture and greater resistance to leakage than manual incisions using a calibrated knife. Furthermore, the fragmentation of the lens provided by the specific pattern of femtosecond laser impacts within the lens significantly reduces the amount of ultrasound used to remove the remaining pieces of the lens during the phacoemulsification phase.

However, despite the femtosecond laser’s high level of technical capabilities in cataract surgery, the clinical benefit for patients remained unclear and a Cochrane meta-analysis could not determine the equivalence or the superiority of FLACS to phacoemulsification due to a very low certainty of the available evidence and the unclear risk of bias in included studies.

With cataract surgery being one of the most routinely performed operations in medicine, it became clear that such a comparison was necessary, not just for patients but for healthcare professionals and decision-makers as well, to enable them to provide recommendations and potentially facilitate the spread of the technology.

The FEMCAT trial was a large-scale, independent, randomised clinical study which took place at five centres in France. It was designed to compare anatomical, visual and refractive outcomes between FLACS and conventional phacoemulsification cataract surgery among 907 patients (1,476 eyes) who received either bilateral or a unilateral cataract surgery by one of these two methods. We included a wide range of cataract severity grades that were likely to be representative of the French population who undergo cataract surgery every year in France.

The success rate was defined by four relevant outcomes in cataract surgery: the absence of perioperative complications up to the 3-month visit; a best corrected visual acuity of 0.0 LogMAR or better; an absolute manifest refractive error below 0.75 dioptres; and the absence of significant change in corneal astigmatism between the preoperative visit at month 3 post-operatively.

The femtosecond laser was found not to be superior to phacoemulsification in cataract surgery and thus FLACS failed to provide an additional clinical benefit for patients despite its advanced technical performance. Indeed, we observed a high rate of uncomplicated surgery of 94.2% up to the 3-month visit without significant difference between the two groups. These results were recently reported in 

The rate of absolute manifest refractive error below 0.75 dioptres or 0.5 dioptres were up to 81.4% and 76.5%, respectively, again without significant difference between the two groups (Figure 2). Interestingly, we did not observe any difference in visual, refractive or anatomical outcome measures between the two groups whatever the cataract type or the cataract severity grade.

In order to provide robust data on a large sample size, the FEMCAT trial was designed to minimise the risk of bias. We strived to provide masking procedures until the last follow-up visit wherever we could, including having a sham laser procedure for patients randomly allocated to the phacoemulsification group. Additionally, an independent adjudication committee composed of three independent ophthalmologists masked to the trial allocation was designated to evaluate all adverse events for increasing objectivity in safety evaluation.

We also standardised all the associated procedures (IOL optical and biomaterial characteristics or phacoemulsification machines) in each centre to limit the risk of bias and to analyse only the safety and efficacy profile of the studied surgical procedures. Finally, four surgeons experienced in cataract surgery were involved in the trial at each centre. They were also likely to be representative of cataract surgeons in France.

FEMCAT was also a cost-effectiveness trial and so we collected all direct expenses related to the surgery using a real-life micro-costing approach based on detailed resources used during the surgery. It included the prices of items such as knives, viscoelastic products, syringes or cannulas; the expense of the laser and disposable docking systems; and all costs related to phacoemulsification machines.

We also estimated all inpatient and outpatient costs, including those related to the follow-up or rehabilitation care arising until the treatment success measurement was obtained using the French

national health data system, a claim database encompassing 98

.8% of the French population. With comparable clinical outcomes between the two groups, the cost of FLACS was significantly higher and thus the laser was found not to be a cost-effective procedure for cataract surgery.

Indeed, all inpatient and outpatient costs as well as all direct costs of surgical items or phacoemulsification machines were not significantly reduced in the FLACS group. Thus the financial loss incurred by laser was not compensated, even in part, by either better clinical efficacy or a significant reduction in other direct costs during the surgical procedure or thereafter.

It is likely that the technology’s expansion will need to be facilitated by a significant reduction in femtosecond laser procedure costs in the future, including those incurred indirectly, for example by phacoemulsification machines that are used to aspire the fragmented lens.

The femtosecond laser was confirmed to be reliable and precise regardless of the cataract severity grade or the clinical experience of surgeons in our trial. Also noteworthy was that the laser enabled reliable images of the anterior structure of the eye to be obtained irrespective of the cataract severity grade, even for very mature cataracts, and allowed for reproducible cuttings of ocular tissues in the FLACS group.

Moreover, we did not observe any significant adverse event during the femtosecond laser phase. We reported only six cases of incomplete capsulotomy without subsequent anterior capsule tear.

Ultrasound time and energy were also significantly reduced in the FLACS group. Finally, we can also confirm the learning curve of FLACS was short without significant adverse events seen in the first cases by each surgeon.

While FLACS does not provide an additional clinical benefit for patients over phacoemulsification cataract surgery today and was not found to be a cost-effective strategy in our trial, it is fair to acknowledge that this technology is still in its infancy and some perspective exists. Indeed, FLACS has provided new insights into anterior segment surgery, particularly in paediatric cataracts, by enabling posterior laser capsulotomy, which, when it is performed following crystalline lens extraction, could limit the risk of amblyopia related to the posterior capsule opacification.

Additionally, owing to the real-time imaging technology and the three-dimensional zones of laser treatment or safety zones the surgeon can define prior to the laser procedure, this technology can also improve the surgical outcomes of some severe anterior segment diseases such as severe capsulophimosis. The development of new IOLs that would be a better fit to the very precise and circular capsulotomy provided by the femtosecond laser machine could also help improve IOL stability or centration along the visual axis.

Furthermore, innovations such as new aspiration machines associated with the femtosecond laser could help limit the need to use the phacoemulsification machine and reduce the overall cost of the surgical procedure. Finally, FLACS may also pave the way to a new era of automation and robotics in cataract surgery.

In conclusion, we believe that the FEMCAT trial provides useful information that healthcare providers and decision-makers should consider before implementing this new technology in routine practice for cataract surgery. Although FLACS represents an innovation that could open new doors in ophthalmology, it is necessary to rationalise the overall costs of cataract surgery as well as consider the individual patient’s journey when considering whether or not it is appropriate to choose FLACS over phacoemulsification.

Figure 1. Real-time imaging system showing an automated recognition of anterior and posterior faces of the cornea, and anterior and posterior faces of the lens. The green zone is the laser treatment zone within the lens and the red zone is the safety zone based on the pupillary margin and the posterior capsule of the lens. 

(Image courtesy of Dr Cédric Schweitzer)

Figure 2. FEMCAT trial: Safety and efficacy analyses at 3 months in modified intent-to-treat populations.

Dr Schweitzer is an ophthalmologist at Bordeaux University Hospital in France and is the principal investigator of the FEMCAT trial, which was fully supported by a grant for the French ministry of social affairs and health. The French ministry of social affairs and health did not participate in the collection, management, statistical analysis and interpretation of the data or in submitted manuscripts. Dr Schweitzer has no financial disclosures.

With its higher costs, FLACS failed to provide an additional benefit over phacoemulsification for patients or in healthcare settings, despite its advanced capabilities.

Femtosecond lasers and phacoemulsification go head to head in French trial

Much has been published about the risks of contracting Covid-19 from tears and the precautions that need to be taken. This article will evaluate the risks surrounding the most commonly performed procedures during an ophthalmic exam, focusing particularly on procedures requiring contact with the eye, such as tonometry.

Given that the COVID-19 pandemic involves a new virus, which has spread and behaved unpredictably, our understanding of patient management in this new reality has evolved. Consider that in March, a study published in the journal 

 concluded that it was unlikely that COVID-19 patients shed virus through their tears.

However, less than two months later, a new study from Johns Hopkins University, Baltimore, United States, concluded differently: “These results indicate that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus.”

 They added that the results showed that the ocular surface could be an even more significant reservoir for virus particles than suggested by other recent clinical studies.

Given these recent findings, we must be vigilant about reducing the risk of virus transmission for our staff, as well as our patients. In our clinic, we have implemented specific safety measures that should reduce the risk of infections in general.

These include: providing face masks to each patient when entering the clinic; measuring body temperature by a non-contact method; excluding patients with any potential COVID-19 symptoms; frequent ventilation of all rooms; adding barriers around instruments and the reception area; and disinfection of all surfaces every hour. We have also made it mandatory for the entire clinic team to wear gloves, safety glasses and facemasks.

According to a World Health Organisation-funded study, face masks and eye protection/safety glasses provide the best protection in reducing the risk of infection. Writing in the 

 the researchers looked at 216 studies with more than 25,000 COVID-19 patients and found that face masks resulted in the largest reduction of risk (95% CI: 0.07–0.34), followed by eye protection (95% CI: 0.12–0.39).

In addition, most eyecare practitioners very quickly adopted the placement of a plastic barrier around their slit lamps in order to reduce transmission risk. But what about other routine eye exams – what are the risks and how can we minimise them?

Among the first recommendations made by the American Academy of Ophthalmology and other ophthalmic societies was to place a plastic shield around the exterior of slit lamps.

A recent study published in a letter to the editor in the British journal 

 tested two sizes of plastic shields using a breathing simulator to replicate a normal adult breathing pattern.

Researchers measured spray without the plastic barrier, with an 11x11x0.2-cm barrier and a larger 45x44x0.2-cm barrier.

They then measured the number of particles over a 1-minute period. The slit lamp arm was offset at 60° and the test was repeated five times for each shield. A linear regression analysis determined the effectiveness of no barrier and the two barriers, as well as the particle count.

Without any shield in place, the mean log particle count was 3.59 (95% CI: 3.48–3.70). With the standard shield in place, there was a reduction to 3.01 (95% CI: 2.90–3.13; 

<0.01) and a further drop was seen with the larger barrier in place, which lead to a mean count of 2.62 particles (95% CI: 2.50–2.73; 

However, while the larger barrier provided the greatest reduction in particle transmission, the authors pointed out that the larger shield can lead to contact transmission of the virus due to the need to manipulate the slit lamp arm or during tonometry. As a result, the authors noted that the barrier should be used in combination with hand hygiene and surface cleaning.

A highly useful article published in the June issue of the journal 

 outlines the risks and best practices for various ophthalmic tests, including the use of imaging devices, such as those used for optical coherence tomography. The obvious contact points on these devices are the chin rest and head guard where the patient has direct contact, but if the patient is unmasked, droplets from breathing and speaking can also contaminate the surface of the device.

While cleaning and disinfection after each patient is the obvious solution, most imaging device manufacturers have specific recommendations about how this is done without damaging these devices. All manufacturers have developed guidelines for this purpose.

This test places both the patient and the technician at risk due to its lengthy nature and the need for the technician to be in proximity to the patient while the patient is performing the visual field test. The corrective lens and bowl of the perimeter can be exposed to respiratory droplets, while the response button, occluder, head strap and chin rest are in direct contact with the patient. The authors suggest replacing the occluder with a disposable amblyopia patch or gauze, as well as following manufacturers’ cleaning and disinfecting instructions.

This procedure has attracted a certain amount of debate given that the two forms of tonometry—contact and non-contact— have the potential to result in infection transmission.With contact tonometry, the risk is clear from the name – the tonometer encounters the cornea.

Published studies have shown that applanation tonometry can potentially transmit a number of infectious diseases, including adenovirus B and herpes simplex virus 1, while reusable tonometer prisms are able to transmit hepatitis B & C, as well as HIV and Creutzfeldt-Jakob disease.

 The AAO notes that there is no optimal way to disinfect Goldmann tonometers without potentially damaging the device and recommends the use of disposable tonometer prisms, if available, to reduce the risk of viral transmission.

published online in April, ophthalmologists from the University of Hong Kong noted that they had suspended all tests that might result in micro-aerosol, including non-contact tonometry (NCT).

. note in their article that there is no set evidence that there is aerosol transmission with current devices and also point out that NCT enables clinic staff to put more distance between themselves and patients.

However, surfaces around the testing area should be disinfected between patients. The Centres for Disease Control and Prevention also recommends caution in performing tests that result in “aerosolisation of viral particles.”

Interestingly, a 1991 study of NCTs attempted to show the alleged danger of the air puff approach using fluorescence photography to capture droplet splatter when drops were instilled into eyes as the puff of air was applied. However, they could not replicate it with just the patients’ tears.

Can safety rules make vision exams 100% safe?

Based on our review of literature and recommendations that have been published in recent months, it is clear that both societies and ophthalmic equipment manufacturers are providing as much guidance as possible to help clinicians navigate these unchartered waters. It is also certain that, based on our current knowledge of the role of the tear film in COVID-19 patients, with proper safety, cleaning and disinfecting procedures, the risk of viral transmission will remain low.

Of course, virus transmission can never be completely excluded by the discussed transmission pathways. The remaining risk under these circumstances must be estimated.

Wearing masks and safety glasses is a good barrier against direct droplet transmission even within the proximity between patient and examiner in the case of Goldman applanation tonometry or rebound tonometry. Gloves protect the examiner while he touches the patient’s face and eyes. But care must be taken to avoid cross-contamination of surfaces or other instruments, even when wearing gloves.

In addition to clinic staff wearing masks, it is critical that patients are also masked in order to prevent aerosol contamination from breathing or speaking,

 given that aerosols induced by breathing or sneezing have a much higher virus concentration and are much more likely to be infectious. Recent experiments in clinics have shown that glasses worn by the patient steam up by their breath even when a mask is being worn. This illustrates that aerosol production is difficult to avoid in clinical practice.

These examples demonstrate that potential risks caused by the proximity between patient and examiner in case of applanation and rebound tonometry can be reduced in theory, however, in clinical practice potential risks remain. Again, distancing between patients and examiners and frequent ventilation should be the main ways of minimising these risks, as well as the use of NCT.

The Johns Hopkins study sends a strong message to the ophthalmic community – that ACE2 (the receptor for SARS-CoV-2) and TMPRSS2 (a cell surface-associated protease that facilitates viral entry) are present in conjunctival and corneal epithelial cells. This means that the ocular surface can be a potential site of infection or serve an entry port for the virus to enter the blood stream. In addition, they conclude that ocular virus shedding does have the potential to infect others.

Clearly, in order to provide eye care for our patients, resuming practice is the right thing to do. However, until we have a vaccine and see a reduction of COVID-19 cases down to zero, we must adjust and take every precaution possibly to protect our staff, as well as our patients. The use of tests such as NCT, as well as placement of plastic barriers, provide distance between the clinic team and patients, reducing the risk of aerosol viral transmission.

We have implemented specific safety items in our clinic that should reduce the risk of infections in general. By adhering to these specific safety measures as well as implementing some other rules, we consider NCT measurements to be safe with a very low remaining risk.

The greatest threat to professional healthcare providers arises from the close doctor-patient proximity, which is reduced in the case of NCT measurements. Complete avoidance of tonometry in the clinic could cause much more harm than the very low remaining risk for an infection if all safety rules are considered.

r Kermani is medical director, Augenklinik Neumarkt, Cologne, Germany. He has no financial disclosures.

Seah IYJ, Anderson DE, Kang AEZ, et al. Assessing viral shedding and infectivity of tears in coronavirus disease 2019 (COVID-19) patients. Ophthalmology. 24 Mar 2020. Doi: 

Zhou L, Xu Z, Castiglione GM, et al. ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection. The Ocular Surface. 13 Jun 2020. Doi: 

Chu DK, Akl EA, Duda S, et al. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of sars-cov-2 and COVID-19: a systematic review and meta-analysis. Lancet. 1 Jun 2020. Doi: 10.1016/S0140-6736(20)31142-9.

https://www.aao.org/headline/alert-important-coronavirus-context

Poostchi A, Kuet M, Pegg K, et al. Efficacy of slit lamp breath shields. Eye. 2020;34:1185-1186.

Shabto JM, De Moraes CG, Cioffi GA, Liebmann JM. Review of hygiene and disinfection recommendations for outpatient glaucoma care: A COVID era update. J Glaucoma. 2020;29:409-416.

Shih CK, Chan JCH, Lai JSM. Maintenance of ophthalmic specialist out-patient service during the COVID-19 outbreak: The University of Hong Kong experience. Eye. 2020;34:1241-1242.

Britt JM, Clifton BC, Barnebey HS, et al. Microaerosol formation in noncontact “air-puff” tonometry. Arch Ophthalmol. 1991;109:225-228.

Asadi S, Wexler AS, Cappa CD, et al. Aerosol emission and superemission during human speech increase with voice loudness. Sci Rep. 2019;9:2348.

Until we have a vaccine and see a reduction of COVID-19 cases down to zero, we must adjust and take every precaution possibly to protect our staff, as well as our patients.

Minimising risks during routine ophthalmic examinations in the COVID-19 era

This article was reviewed by Prof. Martin S. Zinkernagel

Anti-vascular endothelial growth factor (VEGF) treatment regimens for neovascular age-related macular degeneration (nAMD) generally aim to dry the neovascular lesion, but evidence suggests that not all retinal fluid is the same. When fluid is present, intraretinal fluid (IRF) is associated with poorer vision.

However, some fluid, particularly subretinal fluid (SRF), may be tolerated.

Admittedly, questions about the impact of refractory SRF on visual outcomes, such as threshold values and duration, continue to be raised. Practitioners nonetheless agree that persistent (i.e., residual) IRF is bad for vision and requires aggressive treatment to maintain sight. At multiple international congress debates in recent months, advocates for and against the need for complete fluid resolution when treating nAMD have presented cogent arguments, shared below.

Based on current clinical data and clinical practicability, outcomes are best if all fluid is treated rigorously when using protocols other than a fixed dosing regimen, argued Prof. Martin Zinkernagel of the University of Bern, Switzerland, at the 19th European Society of Retina Specialists (EURETINA) Congress in 2019 in Paris, France. He pointed to multiple studies which show that improvement of vision correlates with a dry macula and that IRF correlates with poorer final vision.

A zero-tolerance approach to the presence of fluid in nAMD is encouraged, since patients who avoid fluctuations in fluid in the macula may have better visual outcomes. Higher central subfield thickness (CST) variability was associated with lower best-corrected visual acuity (BCVA) gains up until 96 weeks, according to pooled treatment and study data from an analysis of the Phase 3 HAWK and HARRIER nAMD registration studies.

 Although the amplitude of the BCVA gain is individual, more stable CST was associated with both better visual outcomes and a fluid-free retina.

Dr David Brown, Retina Consultants of Houston, United States, who spoke at the American Academy of Ophthalmology (AAO) 2019 Retina Subspecialty Day in October 2019 in San Francisco, US, also cautioned that visual outcomes in nAMD are poorer when fluid is tolerated. In the FLUID study of ranibizumab treat-and-extend for nAMD, up to 40% of patients had refractory IRF and the mean improvement in BCVA overall was no more than 3 letters at 24 months.

 Substantially better visual outcomes have been reported in other proactive anti-VEGF treat-and-extend studies.

Practitioner experience confirms that nAMD patients can tolerate a small amount of SRF with no detrimental effects on visual outcome and it may be helpful in some patients, observed Dr Ramin Tadayoni, Hopitaux de Paris, France, speaking at the 19th EURETINA Congress. Both baseline and persistent intraretinal cystoid fluid have a negative impact on visual acuity despite treatment, while SRF is associated with better outcomes and a lower rate of progression to geographic atrophy.

Eyes with SRF present at baseline had a higher visual acuity improvement than eyes without baseline SRF up to 96 weeks in the Phase 3 VIEW trials of aflibercept (Eylea, Bayer/Regeneron) for nAMD.

 Irrespective of treatment frequency, presence of SRF shows a stable association with better visual outcomes in nAMD.

Further supporting evidence comes from theComparison of Age-related Macular Degeneration Treatments Trials (CATT) study, which showed that foveal IRF is associated with worse visual acuity at year 5 and eyes with foveal SRF had better visual acuity at this time point than eyes that did not.

In the FLUID study, vision outcomes with ‘intensive’ treatment aiming for complete fluid resolution were not significantly better than those seen with a ‘relaxed’ regimen that tolerated some SRF (≤200 µm only at the foveal centre).

Not all retinal fluid is the same, argued Dr Joan Miller, Harvard Medical School, United States, who spoke at the AAO 2019 Retina Subspecialty Day. While some SRF may be tolerated with ongoing treatment, IRF indicates CNV activity and needs to be treated more assertively, she said.

Anatomic improvements (in particular, resolution of IRF) are closely associated with better visual outcomes in nAMD. Clinical studies show that stable subfoveal SRF may be associated with better visual outcomes than persistent IRF.

Recent evaluations from the HARBOR study showed that those patients with residual SRF have the best vision outcomes, suggesting that a dry retina does not necessarily correlate with the best vision gains.17 In a post-hoc analysis of the VIEW trials, eyes with early, persistent IRF were shown to have significantly poorer visual acuity gains than those without residual IRF (Figure 1).

 Furthermore, IRF but not SRF was found to have a detrimental impact on visual acuity over 52 weeks.

In the HAWK and HARRIER studies, superior anatomic efficacy outcomes seen for brolucizumab (Beovu, Novartis) with respect to retinal thickness and fluid did not translate to superior vision gains over standard-of-care aflibercept.

Recommendations on the use of fluid status to guide treat-and-extend regimen decisions with anti-VEGF therapy for nAMD, from a global collaboration of expert ophthalmologists and retinal specialists who presented at the Europe Controversies in Ophthalmology 2020 Virtual Conference (COPHy) in March 2020, are summarised in Table 1. Whilst IRF can be considered a biomarker of disease activity, some persistent SRF may be tolerated. Moreover, improving IRF and/or stable SRF can be managed using maintained or extended treatment intervals.

Treat-and-extend retreatment/extension decisions should differentiate between IRF and SRF to improve patient outcomes, as a zero-tolerance approach to SRF may not be required for optimal outcomes, considered Dr Paolo Lanzetta, University of Udine, Italy, at the 2020 COPHy. Moreover, maintaining or extending injection intervals in the presence of residual SRF can decrease overall patient burden by minimising treatment exposure, he added.

Real-world data suggests that some fluid, particularly SRF, may be tolerated without compromising visual outcomes with maintained retreatment in patients with treatment-naïve nAMD (Figure 2).

  If SRF persists but is stable despite intensive therapy and follow-up, only an increase in SRF may be clinically relevant.

Prof. Zinkernagel is a retina specialist based at the Department of ophthalmology at Bern University Hospital, Bern, Switzerland. He has no financial interest in the subject matter.

Wickremasinghe SS, Janakan V, Sandhu SS, et al. Implication of recurrent or retained fluid on optical coherence tomography for visual acuity during active treatment of neovascular age-related macular degeneration with a treat and extend protocol. 

Lai TT, Hsieh YT, Yang CM, et al. Biomarkers of optical coherence tomography in evaluating the treatment outcomes of neovascular age-related macular degeneration: a real-world study. 

Ritter M, Simader C, Bolz M, et al. Intraretinal cysts are the most relevant prognostic biomarker in neovascular age-related macular degeneration independent of the therapeutic strategy. 

Gianniou C, Dirani A, Jang L, Mantel I. Refractory intraretinal or subretinal fluid in neovascular age-related macular degeneration treated with intravitreal ranibizumab: functional and structural outcome. 

Grunwald JE, Daniel E, Huang J, et al. CATT Research Group. Risk of geographic atrophy in the Comparison of Age-related Macular Degeneration Treatments Trials. 

Guymer RH, Markey CM, McAllister IL, et al. FLUID Investigators. Tolerating subretinal fluid in neovascular age-related macular degeneration treated with ranibizumab using a treat-and-extend regimen: FLUID study 24-month results. 

Dugel PU. Pooled treatment study data for brolucizumab and aflibercept from HAWK and HARRIER. Presentation at the 19th EURETINA Congress, September 5-8, 2019, Paris, France.

Ohji M, Takahashi K, Okada AA, et al. Efficacy and safety of intravitreal aflibercept treat-and-extend regimens in exudative age-related macular degeneration: 52- and 96-week findings from ALTAIR. 

Kertes PJ, Galic IJ, Greve M, et al. Efficacy of a treat-and-extend regimen with ranibizumab in patients with neovascular age-related macular disease: a randomized clinical trial

. 2020 Jan 9. doi: 10.1001/jamaophthalmol.2019.5540. [Epub ahead of print]

Schmidt-Erfurth U, Waldstein SM. A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration. 

Waldstein SM, Simader C, Staurenghi G, et al. Morphology and visual acuity in aflibercept and ranibizumab therapy for neovascular age-related macular degeneration in the VIEW trials. 

Schmidt-Erfurth U, Klimscha S, Waldstein SM, Bogunović H. A view of the current and future role of optical coherence tomography in the management of age-related macular degeneration. 

Jaffe GJ, Martin DF, Toth CA, et al. Comparison of age-related macular degeneration treatments trials research group. Macular morphology and visual acuity in the comparison of age-related macular degeneration treatments trials. 

Jaffe GJ, Ying GS, Toth CA, et al. Comparison of age-related macular degeneration treatments trials research group. Macular morphology and visual acuity in year five of the Comparison of Age-related Macular Degeneration Treatments Trials. 

Schmidt-Erfurth U, Eldem B, Guymer R, et al. EXCITE Study Group. Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study. 

Sulzbacher F, Roberts P, Munk MR, et al. Vienna Eye Study Center. Relationship of retinal morphology and retinal sensitivity in the treatment of neovascular age-related macular degeneration using aflibercept. 

Sadda SR. Relationship between subretinal fluid (SRF) or intraretinal fluid (IRF) and vision outcomes in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab in the HARBOR trial. Presentation at The Retina Society 2019 Annual Meeting, September 11-15, 2019, London, UK.

Singh RP. Association between early visual function outcomes and anatomic dryness in neovascular age-related macular degeneration. Presentation at The Retina Society 2019 Annual Meeting, September 11-15, 2019, London, UK.

Singer M. Presentation at the 42nd Annual Macula Society Meeting; Bonita Springs, FL, USA, February 13–16, 2019.

Dugel PU, Koh A, Ogura Y, et al. HAWK and HARRIER Study Investigators. HAWK and HARRIER: Phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. 

Gillies MC, Nguyen V, Pilar C, et al. Association between anatomical and clinical outcomes in patients treated with anti-vascular endothelial growth factor for neovascular age-related macular degeneration. Presentation accepted for the Association for Research in Vision and Ophthalmology (ARVO) 2020 Annual Meeting, May 2020.

Recent international ophthalmic congresses have featured advocates for and against the need for complete fluid resolution when treating nAMD, with some ophthalmologists arguing for a zero-tolerance approach to the presence of fluid, and others claiming some residual fluid can be tolerated and may be helpful in some patients. 

Considering the presence of retinal fluid when treating nAMD patients

Since their introduction to the market in the 1960s, lasers have become omnipresent, indispensable devices with areas of application that are as diverse as the types available. For example, lasers are used for reading CDs, DVDs and barcodes at supermarket checkouts.

They can measure the exact distance from earth to the moon; they can take ultra-high-resolution images of living tissue; and they are able to perform surgeries without a scalpel. Lasers even entertain people with light shows. The list goes on.

The word ‘laser’ stands for ‘light amplification by stimulated emission of radiation’. It is a technical device that consists of a medium which is excited through the effect of electrical energy to emit radiation of a specific wavelength. The word was introduced in 1957 by the American physicist Gordon Gold, even before the first laser was constructed.

Also relevant to the development of lasers was the atom model postulated by Niels Bohr in 1913. His ‘planetary model’ demonstrated that electrons can only move in specific orbits around the atomic nucleus.

When energy is supplied, an electron can absorb this energy in order to leave its original orbit and reach an energetically higher one. Conversely, if the electron returns to its actual orbit, it must release the corresponding energy difference, for example, by emitting light.

A short while later, in 1917, the theoretical basis for stimulated amplification of light was postulated by Albert Einstein, in which he described it as the inverse of the absorption by forced radiation. The physicists Rudolf Ladenburg and Hans Kopfermann were able to prove this theory experimentally in 1928.

In the 1950s, research focused on the analogue amplification of microwaves which was perceived to be more promising than the use of light. The American physicists Charles Townes and Arthur Schawlow from Columbia University in New York, United States, were the first to successfully implement Einstein’s hypothesis on stimulated emission. In 1958 they presented their ‘maser’, which stands for ‘microwave amplification by stimulated emission of radiation’.

For his maser, Townes used a beam of ammonia molecules, which was led through a defined cavity. If a molecule randomly emitted a microwave, it could stimulate other ammonia molecules in the container to also emit microwaves of the same frequency.

This led to the intensification of the microwave radiation and the emission of a continuous microwave with a uniform frequency – Einstein’s idea of stimulated emission had thus been realised. The maser can be understood as the predecessor of the laser.

The American physicist Theodore Harold Maiman (1927-2007) received his doctorate in physics in 1955. He was not interested in an academic career but decided to work at Hughes Research Laboratories, owned by eccentric billionaire Howard Hughes and considered as a first-class research company.

With the support of Cold War military funds, Hughes had assembled a team of highly talented researchers. Maiman’s research initially focused on microwaves and maser technology.

He was asked to build a more practical version of the maser by using the chromium atoms in synthetic rubies. The older version of the maser weighed over 2 tons compared with Maiman’s maser, which weighed only 2kg.

He soon became preoccupied with the idea of stimulated emission on the frequency domain of light. His fascination with this concept was so deep that he conducted private research on it.

However, his interest was not in line with the general opinion, which saw no practical application and use for the laser, and so his supervisors banned him from further research on laser technology. After he threatened to resign, the supervisors decided to appease the scientist by providing him with a limited budget of $50,000 and a research assistant for 9 months.

Other international research groups were also exploring laser development. However, progress on the search for a suitable material that could temporarily store energy and then, after being stimulated, emit the energy as a beam of light, stalled. Contemporary research focused on the use of various gases as the active medium and researchers had ruled out rubies as being unsuitable. 

Maiman found promise in rubies; he carefully studied the unsuccessful research results on the substance and found the previous measurements/ calculations by the other researchers to be incorrect. Along with his assistant Charles Asawa, the scientist presented the first ruby laser on 16 May, 1960.

It comprised a finger-sized ruby rod mirrored at both ends (one end with a semi-transparent mirror, because this is where the laser beam should be emitted), surrounded by a commercially available, spiral-shaped flash lamp (which was supposed to stimulate the chrome atoms of the ruby to emit light). This was contained within an aluminum cylinder. The laser emitted a sharply focused red laser light beam (see Figure 1).

The special properties of this new radiation were that it emitted light which was almost parallel and interference-capable (collimation and coherence) of only one specific frequency (monochromatism), which had a very high energy density and which could be focused very accurately.

Maiman’s research results were initially rejected for publication in the journal 

. However, his manuscript went on to be published in 

 in August 1960. Other research groups quickly replicated lasers in countless variations – the triumphal march of the laser was unstoppable.

Hughes still did not believe in the benefits of the laser, so he did not support the research. Maiman subsequently left Hughes Laboratories and founded his own successful company, Korad Cooperation, in 1962, receiving a US patent for his work five years later. 

Many things then happened in quick succession. Obviously, the time was right for the laser: the technological race for the laser had begun. Of the nearly500 research institutes and companies worldwide, 20 to 30 of these developed marketable products. In the following years, solid-state devices such as the ruby laser, various gas, semi-conductor, CO2 and dye lasers came onto the market.

Maiman’s invention was honoured with many awards and accolades. Sadly, while he was also nominated twice for the Nobel Prize several eminent, he never received it. It was particularly appropriate that he himself would benefit from his invention when he was successfully treated with laser surgery for prostate problems at Ludwigs-Maximilian University in Munich, Germany, in 2000.

Thanks to its transparent media, the eye is the ideal part of the body for laser light to be applied. It is therefore not surprising that ophthalmology was the first medical discipline in which a laser was used: the ruby laser was applied to retinal surgery in 1961.

This first attempt turned out not to be overly successful in comparison with Meyer-Schwickerath’s already very sophisticated technology, which had been further developed from its original sunlight coagulator to using a high-pressure xenon lamp.

In the years that followed, the understanding of the effect of laser treatment of the retina improved and its use became optimised. Initially, only the retina was treated.

The work of several eminent scientists since the 1900s has paved the way to modern laser technology, and in turn, provided the diverse ophthalmic applications available today. 

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60 years of laser technology

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