Photobiomodulation (PBM) is the application of monochromatic light to the body with the aim of repairing tissues and reducing inflammation, oedema and pain.

 It has been used for 20 years for the treatment of musculoskeletal pain, injury and dysfunction; to aid wound healing; to improve acute muscle performance and reduce muscle damage after exercise;

 and for neuropathic pain, lymphoedema and oral mucositis.

Several studies in the past 5 years have shown encouraging results using PBM to treat eye diseases including age-related macular degeneration (AMD),

 retinopathy of prematurity and diabetic macular oedema.

 PBM does not worsen the disease, has no side effects and is completely non-invasive.

There is no currently approved treatment or cure for the dry form of AMD, which affects 80% of individuals with AMD and tends to progress more slowly than the wet type.

PBM is not a heat therapy but is more akin to photosynthesis in plants, in that light, in the far red and near-infrared spectral range, can stimulate cells and lead to a cascade of photochemical reactions.

What happens first is that the low-powered light is absorbed locally by cytochrome c oxidase. Mitochondrial energy is then produced by releasing oxygen, which results in increased ATP concentration and reduced oxidative stress.

This photochemical reaction activates enzymes and second messengers, which lead to a cellular and, indirectly, a systemic response in tissues that have not absorbed photons.

 Mitochondrial dysfunction and oxidative stress play a key role in many macular diseases, so PBM is of use in acute and chronic eye diseases.

We offer nine PBM therapy cycles within approximately 1 month. During the procedure, a medical device with light-emitting diodes stimulate cellular function and improve energy production.

Each cycle of therapy delivers wavelengths in the range of 590–850 nm for 4 minutes per eye. Clinical outcomes are determined immediately after the final cycle, after 3 months and after 6 months, using optical coherence tomography (OCT) imaging, the Amsler grid, the Pelli-Robson chart, a Snellen chart and a Jaeger chart.

Nine PBM cycles were administered over 1 month to a patient with dry AMD, after which OCT showed reduced drusen and the patient obtained subjectively improved vision. The patient also experienced less eye strain, more colour contrast, higher definition and better far and near uncorrected visual acuity.

Contrast sensitivity improved from 1.8 to 2.0 log units. Outcomes remained stable at the 6-month follow-up.

This case demonstrated a successful non-invasive treatment with improved quality of vision in dry AMD. Irradiation could therefore offer a new non-invasive, adverse-effect-free means of stimulating retinal stem cells to regenerate.

To date, there are no approved treatments for many retinal diseases. With its ability to promote cellular regeneration using light waves, PBM has resulted in better visual acuity, contrast sensitivity and a less-damaged macular profile in several patients with dry AMD.

Overall, these results are encouraging. Our protocol seems to offer an extremely promising approach to prevent visual acuity from worsening and to promote tissue repair in this form of AMD. Moreover, this method has the enormous advantage of being entirely non-invasive.

According to this hypothesis, irradiation at certain wavelengths can regenerate retinal cells. Thus, modulated light can offer a novel valid therapeutic approach for dry AMD, which has the potential to facilitate the repair of damaged tissues in the retina and promote survival and functions of epithelial cells within the retinal pigmented epithelium.

Drs Pinelli, Bertelli and Scaffidi are based at the Switzerland Eye Research Institute, Lugano. They have no financial disclosures to reveal.

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Holanda VM, Chavantes MC, Wu X, Anders JJ. The mechanistic basis for photobiomodulation therapy of neuropathic pain by near infrared laser light. 

Baxter GD, Liu L, Petrich S, et al. Low level laser therapy (photobiomodulation therapy) for breast cancer-related lymphedema: a systematic review. 

Zadik Y, Arany PR, Fregnani ER, et al. Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines. 

Ferraresi C, Kaippert B, Avci P, et al. Low-level laser (light) therapy increases mitochondrial membrane potential and ATP synthesis in C2C12 myotubes with a peak response at 3-6 h.

Koev K, Avramov L, Borissova E. Clinical results from low-level laser therapy in patients with autosomal dominant cone-rod dystrophy. 

Merry G, Devenyi R, Dotson R, et al. Treatment of dry age-related macular degeneration with photobiomodulation. Presented at The Association for Research and Vision in Ophthalmology (Fort Lauderdale). 2012.

Natoli R, Valter K, Barbosa M, et al. 670nm photobiomodulation as a novel protection against retinopathy of prematurity: evidence from oxygen induced retinopathy models. 

Tang J, Herda AA, Kern TS. Photobiomodulation in the treatment of patients with non-center-involving diabetic macular oedema. 

Markowitz SN, Devenyi RG, Munk MR, et al. A double-masked, randomized, sham-controlled, single-center study with photobiomodulation for the treatment of dry age-related macular degeneration. 

Huang YY, Chen AC, Carroll JD, Hamblin MR. Biphasic dose response in low level light therapy. 

Natoli R, Zhu Y, Valter K, et al. Gene and noncoding RNA regulation underlying photoreceptor protection: microarray study of dietary antioxidant saffron and photobiomodulation in rat retina. 

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Articles

Photobiomodulation has been demonstrated to improve quality of vision in several patients suffering from dry AMD.

Harnessing the power of light in dry age-related macular degeneration

After a team of researchers at the University College London (UCL) Institute of Ophthalmology (IoO), London, started to explore the causes of malformed blood vessels in the eye, they discovered that a molecule called LRG1 (leucine-rich alpha-2-glycoprotein 1) was partly responsible. They realised that if they could block the function of this molecule, they might be able to improve the formation of blood vessels so they would not be as leaky.

The team is now collaborating with Moorfields Eye Hospital, London, with the aim of moving towards clinical testing of new therapies that could improve disease outcomes in patients with a range of disorders including wet age-related macular degeneration (AMD), diabetes and cancer. I spoke with professors John Greenwood and Stephen Moss, who led the team at UCL, to find out more.

Our research began in 2005, when Professor Mark Gillies, a clinical colleague from Sydney, Australia, invited us to join the MacTel Project, a new international consortium set up by the Lowy Medical Research Institute to understand the mechanism behind the rare retinal condition macular telangiectasia type 2, or MacTel. The disease leads to a permanent loss of central vision and at the time, little was known about its causes.

The MacTel Project provided us with almost one million pounds over 5 years, funding which enabled us to see which genes and biological mechanisms were involved in abnormal vessel formation in the retina. This was a hallmark feature of MacTel, and thought to be a cause of the condition, although it was subsequently found to be one of its consequences.

, which we found was implicated in the growth of abnormal blood vessels. We realised that the LRG1 molecule might be a factor not just in MacTel, but in other eye conditions and in diseases affecting other parts of the body. At the time, there were fewer than ten publications on it, and almost nothing was known about its function.

What did you do after finding your target?

We developed a function-blocking humanised monoclonal antibody against the LRG1 protein, ‘Magacizumab’. It has already been through preclinical testing and it looks extremely promising.

More recently, we have generated a Fab fragment (an antigen-binding fragment) from our antibody: ‘MagaFab’. Rather like how Lucentis (ranibizumab, Novartis), the Fab fragment of anti-tumour drug Avastin (bevacizumab, Roche), is used for retinal disease, our aim is for Magafab to be used in eye conditions, with Magacizumab having systemic applications.

Importantly, in the context of eye disease, we have learnt that inhibiting LRG1improves clinical outcomes and reduces lesions in animal models of ocular disease. It does this totally independently of vascular endothelial growth factor (VEGF), which is the key target for most ocular treatments, such as Avastin and Eylea (aflibercept, Regeneron Pharmaceuticals). This means we have identified a completely separate pathway that may explain why some patients do not respond to current treatments.

Could you tell me about the process of developing the antibody?

It took us 4 years to generate the antibody and then engineer it so it could be used in patients without causing an immune response. We then had it manufactured, via good manufacturing practices, through a contract research organisation in San Diego, United States.

However, in preclinical studies, the full-length antibody caused an acute inflammatory response in the eye. There is always a risk that a protein may cause some inflammation, but this was a real puzzle for us, because antibodies being injected into the eye have a long history of being very safe and non-toxic.

We thought this would set us back, but then we got some seed-funding through the UCL Technology Fund, which enabled us to produce the Fab fragment, thus removing the unneeded half of the molecule which we thought might be eliciting the inflammatory response.

This time, preclinical studies yielded no adverse events. In addition, since MagaFab is a smaller molecule, more of it can be contained in solution, which means you can inject a larger, longer-lasting dose.

We have also been researching its role in cancer, as well as collaborating with scientists working on lung disease, colitis and vascular inflammation, where LRG1is also emerging as a contributing factor in disease progression. This opens up the possibility of using Magacizumab to treat patients systemically – something we were able to do without problems in our earlier safety studies. In particular, we have shown that our antibody reduces the growth of many solid tumours, and enhances the effectiveness of existing therapies such as cytotoxics and the new immunotherapies.

How does LRG1affect vasculature and thus lead to disease?

LRG1seems to affect the capacity of a blood vessel to mature and stabilise. When blood vessels grow during development, pericytes crawl along the endothelial cells which line the vessel wall.

Through interactions between these two cell types, the new vessels stabilise and the junctions between them start to become impermeable. If you disrupt this interaction, the vessels fail to stabilise and instead retain an immature and abnormal, leaky characteristic.

We think LRG1 affects the pericytes by preventing crosstalk, so blood vessels remain fragile and haemorrhagic; indeed, if we inject the molecule into the eye as the vasculature is developing, it disrupts the vessels and prevents them from growing normally. In diseases we have looked at, ranging from diabetic eye disease to cancer, LRG1 is switched on in the affected blood vessels.

This might explain why, in nearly every disease you look at, vessels do not grow normally. This opens up the possibility that LRG1 may be involved in the early stages of diabetes, where pericytes are one of the first cell types to be affected.

We know that the gene gets switched on very early in diabetes – you suddenly see levels go shooting up, even before you start to see the pathology, which is very interesting. And our studies show that LRG1 is certainly involved in the later, proliferative stage of diabetes. In fact, in both prolific diabetic retinopathy and wet AMD, when we look in the eyes of patients, we find high levels of LRG1.

We would like to see MagaFab succeed in the early-stage trials by showing that it is safe and can be tolerated in patients. Ultimately, however, we would like to see some clinical benefit for the large cohort of patients with wet AMD and diabetic eye disease who either do not respond to current treatments or respond poorly. Given how common these diseases are, if our therapy is able to meet the needs of a significant number of those patients, it has the potential to impact hundreds of thousands of people globally.

The fact that so many patients do not respond to anti-VEGF treatment indicates that processes other than the VEGF pathway are important. The same is true for cancer, which can bypass the VEGF pathway.

However, we think that because of what we know about the mode of action of the LRG1 molecule, diabetic patients may be more likely to benefit. This is because more of them fail to respond to anti-VEGFs than for wet AMD: around 50% non/poor responders in the early, diabetic macular oedema stage. We have evidence that our therapy might be good at that point, as well as later on, when you have new vessel formation.

This also raises the possibility—and this is speculation—that MagaFab would be beneficial in other eye diseases where abnormal vasculature is a problem, such as retinopathy of prematurity and inherited diseases such as Coats disease and familial exudative vitreoretinopathy.

If we can prove it is safe in the eye, then these can all be investigated. Outside of ophthalmology, we are hoping to take the full-length antibody (which is safe in the rest of the body) to cancer trials.

We have created PanAngium Therapeutics, a spin-out company, which is about to seek its first series A funding from external investors for the ophthalmic work. That would enable us to scale-up production of MagaFab and then design and embark on appropriate early-stage clinical trials, probably starting two years from now.

We will be relying on our Moorfields colleagues and the information they have about patients to identify the inclusion and exclusion criteria for potential participants into the trial. A visual acuity test will be our primary outcome measure – this is the gold standard, although we will also be measuring a number of secondary outcomes. These include optical coherence tomography scans to look at retinal thickness and, potentially, adaptive optics scanning laser ophthalmoscopy to detect vessel structure.

Prof. Moss holds the Norman Ashton Chair of Biomedical Research at the UCL Institute of Ophthalmology. He is a named inventor on several patents relating to annexins and to LRG1 and is a founder and hold equity in PanAngium Therapeutics.

Prof. Greenwood is the Hugh Davson Professor of Biomedical Research at the UCL Institute of Ophthalmology, University College London. He is an inventor on several patents relating to LRG1, and is a founder and holds equity in PanAngium Therapeutics.

Novel monoclonal antibody can halt the growth of abnormal blood vessels

Uncovering the role of LRG1 in disease mechanisms 

Patients judge the success of modern cataract and refractive surgery by the degree of spectacle independence they achieve. Distance vision after cataract surgery is taken for granted, so patients are usually disappointed when they need glasses for driving and watching TV.

The need for glasses after cataract surgery is often due to a residual refractive error, including spherical and astigmatic errors. However, accurate biometry with modern optical biometers can negate spherical errors. Astigmatism, mainly corneal in origin, is a common refractive error in the cataract age group.

Prior to surgery, corneal astigmatism of more than 0.75 D and of at least 1 D is found in 23.9% and 41.2% of patients, respectively.

 Astigmatism can be addressed at the time of cataract surgery by toric IOL implantation or astigmatic keratotomies.

Patients are also starting to request adequate intermediate and near vision without glasses after cataract surgery. Several presbyopia-correcting premium IOLs are available to address this issue. However, astigmatism greatly influences the function of these lenses and may result in patient dissatisfaction.

Astigmatism reduces quality of vision, whether the patient receives a monofocal or a multifocal lens. In one study comparing the effect of astigmatism on the visual function of both types of IOLs—with astigmatism of 1.50 D or more—the corrected distance visual acuity and the distance-corrected intermediate visual acuity at 0.5 m were significantly worse in the multifocal IOL group than in the monofocal IOL group.

The appropriate cut-off postoperative astigmatism to achieve optimal visual function is considered to be 0.5 D or less. Nevertheless, subjective perception of halos and glare after multifocal IOL implantation is correlated with the amount of postoperative residual astigmatism.

If residual astigmatism is between 0.25 and 0.75 D—less than 1 D—the patient is usually satisfied and the quality of vision is not disturbed. However, if the astigmatism is beyond 0.75 D, the quality of vision is significantly decreased.

Residual astigmatism following cataract surgery

One of the leading causes of residual astigmatism after cataract surgery is the inaccurate preoperative measurement of corneal astigmatism. Most Placido topographers and keratometers measure corneal astigmatism based on anterior corneal radius measurements and assume that the posterior corneal surface has a fixed ratio of 82.2% to the anterior corneal surface.

However, the principal planes of the anterior and posterior surfaces differ from one another, even in normal eyes. Furthermore, the posterior corneal surface might contribute to total corneal astigmatism, or total keratometry (TK), more than we thought.

The contribution of posterior corneal astigmatism to TK was explored by Koch et al. in 2012.

 They showed continuous drift of the steep meridian on the anterior corneal surface from vertical to horizontal with increasing age, whereas the steep meridian on the posterior corneal surface remains substantially vertical and stable with age.

The magnitude of posterior corneal astigmatism showed no or weak correlation to the anterior corneal astigmatism if the axis on the anterior surface was oblique or horizontal. They concluded that anterior and posterior corneal astigmatisms are not necessarily correlated, and that posterior corneal astigmatism might alter the magnitude and axis of the TK astigmatism.

For accurate preoperative measurement of corneal astigmatism, it is essential to take posterior corneal astigmatism into account. Modern toric IOL calculators empirically predict posterior corneal astigmatism for more precise postoperative results. However, precision is achieved by measuring, not predicting.

Tomography devices based on Scheimpflug images can measure posterior corneal astigmatism with moderate accuracy. Given that measurements must be converted to equivalent standard keratometry readings before using a biometry formula, it seems to be impractical for everyday refractive/cataract surgery.

 I primarily rely on swept-source optical coherence tomography (OCT) biometry (IOLMaster 700; Carl Zeiss Meditec AG) because it allows for accurate measurement of corneal astigmatism on both the anterior and posterior surfaces.

This technology measures the curvature of the anterior corneal surface followed by corneal thickness: by fitting this measurement to the anterior corneal curvature, the posterior corneal curvature can be accurately calculated. Calibration is then applied to these posterior corneal surface curvature values to ensure that TK is compatible with the existing IOL power calculation formula and constants.

A 57-year-old man with astigmatism requested a presbyopia-correcting IOL. His delta K was +0.80 D, beyond the 0.75 D cut-off threshold noted in the previous paragraph (see Figure 1). This amount of astigmatism needs to be corrected prior to implanting a multifocal premium IOL to obtain spectacle independence for distance and for near vision; based on this delta K, I should implant a multifocal toric IOL.

However, if I consider the posterior corneal measurement, I can see that just to the right of this number, the delta TK is 0.56 D. In this case, the true amount of corneal astigmatism was less than expected when we measured the anterior corneal surface only. The delta K of 0.80 is not the true number; the true delta TK is 0.56 D.

Thus, I can implant a presbyopia-correcting IOL knowing that it will not interfere with the quality of vision of this patient’s eye. There is no harm in leaving this amount of astigmatism because it is very low and will not interfere or affect visual quality with the presbyopia-correcting lens.

Now that we have devices that calculate total corneal astigmatism, cataract and refractive surgeons can make more precise measurements, which translates to more patients who have spectacle independence and better quality of vision because we are targeting emmetropia closely. All in all, astigmatism should be measured, not predicted.

Prof. Assaf is based at the Faculty of Medicine, Ain Shams University, Cairo, Egypt. He has no financial interests in the subject matter.

Ferrer-Blasco T, Montés-Micó R, Peixoto-de-Matos SC, et al. Prevalence of corneal astigmatism before cataract surgery. 

Berdahl JP, Hardten DR, Kramer BA, Potvin R. Effect of astigmatism on visual acuity after multifocal versus monofocal intraocular lens implantation. 

de Vries NE, Webers CAB, Touwslager WRH, et al. Dissatisfaction after implantation of multifocal intraocular lenses. 

Hayashi K, Manabe S, Yoshida M, Hayashi H. Effect of astigmatism on visual acuity in eyes with a diffractive multifocal intraocular lens. 

Holladay JT, Hill WE, Steinmueller A. Corneal power measurements using scheimpflug imaging in eyes with prior corneal refractive surgery. 

. 2009;25:862–868 [published correction appears in 

Symes RJ, Ursell PG. Automated keratometry in routine cataract surgery: comparison of Scheimpflug and conventional values. 

Koch DD, Ali SF, Weikert MP, Shirayama M, et al. Contribution of posterior corneal astigmatism to total corneal astigmatism. 

Data on file (IOLMaster 700, Carl Zeiss Meditec AG).

The possibility of taking precise measurements of total corneal astigmatism enable more patients to be spectacle-free following cataract surgery.

The role of astigmatism in cataract surgery with premium IOLs

The increase in life expectancies and lifestyle changes have resulted in an increasing number of patients requesting spectacle-independent near and intermediate vision for their daily activities, aside from excellent distance vision. Presbyopia-correcting IOLs are also a treatment option for presbyopic patients who are not candidates for laser refractive surgery and do not want to rely on reading glasses. Over recent years, a wide spectrum of multifocal (MF) IOLs has been developed.

Presbyopia-correcting IOLs can be divided into three broad categories: MF IOLs (including diffractive or refractive designs), extended depth-of-focus (EDOF) IOLs and accommodative IOLs (intracapsular or sulcus placed).

 EDOF IOLs, or extended range-of-vision IOLs, are a relatively new technology in the treatment of presbyopia.

The basic optical principle is to create a single-elongated focal point to enhance the depth of focus, on the contrary to monofocal IOLs (in which light is focused on one single point) or MF IOLs (which has two or three discrete points). The idea of EDOF is not new.

Over 30 years ago, Nakazawa and Ohtsuki reported apparent accommodation in 39 eyes implanted with spherical IOLs.

 The authors found that the depth of field in these cases was inversely proportional to the pupillary diameter.Since then, several optical strategies have been used to extend the depth of focus at both the cornea and lens plane.

However, the term EDOF should be limited to those IOLs in which a manipulation has been made in their aberrometry profile to enlarge the depth of field.Those IOLs which have a MF design and, on top of it, also offer a manipulated aberrometry optical profile, should be called ‘hybrid EDOF IOLs’.

The first so-called EDOF IOL, which is really a hybrid EDOF (Tecnis Symfony, Johnson and Johnson Vision) was introduced into the European market in June 2014 and subsequently approved for use in the United States in 2016.

 Since then, several EDOF-labelled IOLs, many of them not really based on the EDOF principle, have been released.

Spherical aberration (SA) is associated with focal length difference between the central and marginal ray where the light enters in the lens (Figure 1A). For any given eye, the Zernike coefficients may vary widely, but a mean value of corneal spherical aberration is +0.31 ± 0.135 μm for a 6-mm pupil size.

It was shown that aspheric IOLs which effectively reduce spherical aberration improve the optical quality over spherical IOLs.

 On the other hand, higher positive SA in eyes having received an aberration-free IOL results in a better distance-corrected near visual acuity than that following implantation of negative-SA IOLs (that have reduced corneal SA).

 Similarly, intentional induction of SA within the IOL design can increase the depth of focus.

Chromatic aberrations (CAs) are associated with focal length difference between the visible spectrum of different colours of light (Figure 1B). The human cornea produces a CA, in which blue light is diffracted more than red light.

The optical design also has an impact: a refractive optic maintains the same CA of the cornea, so with this lens the final ocular CA will increase, as will the dispersion of the wavelengths. On the contrary, diffractive IOLs can reverse CA: red blends more than blue.

So, diffractive IOLs can minimise the CA in every eye. Achromatisation does not bring an extended depth-of-field improvement but rather an improvement in the contrast sensitivity function;

 thus, diffractive could lead to an improvement of the contrast sensitivity and the quality of vision.

The pinhole effect isanother concept which allows a greater depth-of-focus to be obtained. In general, it could be stated that the smaller the pupil size, the greater the depth of field (and depth of focus).

 Following this principle, the use of an opaque pinhole mask in a monofocal IOL enhances the depth of focus.

Moreover, the Stiles-Crawford effect could be additionally possible; it is believed that when an equal intensity of light enters near the centre of the pupil, it produces a greater photoreceptor response compared with the light entering the eye near the edge of the pupil.

EDOF IOLs provide a continuous range of focus without a clearly asymmetric IOL power distribution. This elongated focus is introduced to eliminate the overlapping of near and far images caused by traditional multifocal IOLs and the halo effect; ideally EDOF IOLs should enhance intermediate and near visual performance, while minimally affecting distance vision. In this way, EDOF IOLs differ from multifocal IOLs, in which the secondary out-of-focus images correspond to the additional foci and might induce halos. 

Today, there is a relevant interest in the new models of presbyopic IOLs; several IOLs are marketed as EDOF IOLs. We encounter a confusion in the terminology; some of the so-called EDOF lenses are really MF lenses with low near-add power, in which part of the additional optical power has been withdrawn to avoid the overlapping of images and the consequent halos and glare.

We believe that it is necessary to clarify the current nomenclature and differentiate two types of EDOF IOLs: pure EDOF IOLs and hybrid MF-EDOF IOLs (Figure 2).

 Pure EDOF IOLs are based on the spherical aberration-based optics or the pinhole effect, but have no multifocality.

To name a lens a pure EDOF IOL, the optical profile has to be continuous, without a change in the optical transition of the optical profile. This rule is equal for both the refractive and diffractive MF IOL models. All the lenses that employ correction of CAs, have a diffractive/diffractive-hybrid profile or an additional power to increase the near vision are not pure EDOF IOLs.

The trade-off of inducing certain amounts of ocular aberrations is the potential degradation of quality of vision. This also limits their performance; their near vision capability is usually limited to about 1 diopter.

Those IOLs that have attempted to provide more are either no longer on the market, no longer available because the originator company has closed or they have produced very bad results.The reason for the latter is that for the first time we are able to see the retinal image quality with pyramidal aberrometry and the results are very different.

On the other hand, multifocality and EDOF characteristics are not exclusive of each other. A bifocal IOL may exhibit EDOF characteristics, likewise with an aspheric monofocal IOL or even a diffractive or refractive trifocal IOL. For example, the Tecnis Symfony is an IOL which combine an EDOF with multifocality. We propose naming such lenses ‘hybrid MF-EDOF IOLs’ (Figure 2).

Hybrid MF-EDOF IOLs include diffractive-EDOF IOLs, refractive-EDOF IOLs and diffractive-refractive-EDOF IOLs. Some IOLs named as ‘EDOF’ are really only MF lenses with a low near-vision add and no EDOF component (an example of this confusing commercial terminology is the Zeiss LARA, whose neutral asphericity makes it a low-near vision add multifocal rather than an EDOF).

Optical bench reports and clinical outcomes

Several optical bench reports have shown that the EDOF lenses provide better optical quality on the whole addition range than MF and monofocal lenses.Nevertheless, assessment of the quality of vision and optical/refractive performance of EDOF IOLs can be challenging due to the wide array of procedures available for evaluation of these lenses.

In some cases, even if the optical laboratory benchmark study showed that an IOL has supreme optical properties, the results were not always correlated with patient satisfaction and spectacle independence in clinical trials. For example, the initialresults of the WIOL-CF performance were presented in an observational study made by a Czech research group; they indicated excellent visual acuity for far and intermediate vision, and reasonably good near vision with minimal optical phenomena.

Although the preliminary data were encouraging, recent investigations revealed a high rate of poor vision quality and a consistent pattern of spontaneous dislocation of the lens. The lens was withdrawn from the market and the company ceased commercial activities in October 2018.

For several other IOL types, the currently available clinical evidence is limited. The 2017 American Academy of Ophthalmology Task Force consensus statement on EDOF lenses requires:

1) A minimum of 100 patients with EDOF lenses;

2) Depth of focus defined as the interval of nonpositive defocus values with a mean visual acuity of at least 0.2 logMAR; and

3) A depth of focus set at least 0.5 D wider than for the monofocal control group at 0.2 logMAR.

However, none of the currently published studies fulfills all the aforementioned requirements.

In practice, EDOF lenses provide excellent intermediate vision, but inadequate quality of vision for near distance.

 We believe EDOF lenses should be used as monofocal lenses with a minor improvement for near vision; they can be expected to provide bad quality of near vision, while intermediate vision can be adequate.

One of the ways to compensate the insufficiency in near visual acuity in patients with EDOF lenses is mini-monovision, or mix-and-match strategies with diffractive low-add lenses; nevertheless, using the mini-monovision may cause a decrease in far vision and additional halos from the low myopia in the contralateral eye.

 If a patient requires good near vision with an IOL, we believe that they should receive a MF lens (a refractive and diffractive model) making the choice dependent on the patient profile and preferences.

It is not an easy task to make the IOL choice and this is why objective information based on aberrometer internal component information should be required. It is also important to develop a standardised objective means of measuring and reporting visual and refractive outcomes with these lenses, as a guide for clinicians in the future.

Neuroadaptation is a major concern in MF or EDOF IOLs; this process is time consuming and dependent on individual factors (of which some are unknown).

 Pure EDOF lenses with a relevant amount of aberrations to improve near vision may be poorly tolerated by the patient, since although the brain is adapted up to a certain amount of aberrations over time, a sudden increase in aberrations may be problematic. Regarding photic phenomena the evidence is scarce, however, some studies have reported a lower intensity of photic phenomena in EDOF IOLs when compared with MF IOLs.

There is a wide range of IOLs available on the market. A careful and thorough patient examination, taking into account IOL selection based on lifestyle and visual needs, is essential to avoid patient misunderstandings about the expected outcomes. In our recent article,

 there is a biased used of the term EDOF, as some of the IOLs marketed with this name are only MF or hybrid MF/EDOF lenses.

We propose an alternative terminology and naming lenses that have combined optical designs as ‘hybrid IOLs’. Clinicians and surgeons should be aware of this misleading use of the EDOF concept.

Future research will continue towards finding a balance between quality of vision, extended depth of focus and dysphotopsias. Counselling and advice is needed in order to ensure satisfactory outcomes – both for the patient and the surgeon.

Prof. Alió is professor and chairman of ophthalmology at the Miguel Hernandez University of Elche and scientific director at Vissum in Alicante, Spain.

Dr Kanclerz works in private practice at the medical University of Gdańsk in Poland.

Neither author has a financial or proprietary interest in any material or method mentioned.


The study this article is based on1 has been supported in part by the Red Temática de Investigación Cooperativa en Salud (RETICS) (reference number RD16/0008/0012) financed by the Instituto Carlos III – General Subdirection of Networks and Cooperative Investigation Centres (R&D&I National Plan 2008-2011) and the European Regional Development Fund (Fondo Europeo de Desarrollo Regional FEDER).

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Clinicians and surgeons should be aware of the misleading use of the EDOF concept. The authors herein propose an alternative terminology and that lenses which have combined optical designs are referred to as ‘hybrid IOLs’.

Ophthalmology Times Europe October 2020

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