
John A. Hovanesian, MD, clinical instructor, UCLA Jules Stein Eye Institute, Laguna Hills, CA, discusses the highlights of his presentation titled "The D3 Study: Drug Delivery vs Drops — A Prospective Clinical Study Evaluating Dexycu vs Prednisolone Acetate 1% in Controlling Post-operative Pain and Inflammation in Patients Undergoing Sequential Cataract Surgery," during the virtual 2020 American Academy of Ophthalmology (AAO) meeting. 

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John A. Hovanesian, MD, discusses the highlights of his presentation on a clinical study evaluating dexamethasone vs prednisolone acetate 1% in controlling postop pain/inflammation in sequential cataract surgery patients.

Controlling postop pain, inflammation in cataract patients: drug delivery vs drops

Reviewed by Dr Marko Lukic and Dr Thomas A Ciulla

One-year results from a retrospective cohort study that assessed the effectiveness of aflibercept (Eylea, Regeneron Pharmaceuticals) in treatment-naïve patients with diabetic macular oedema (DMO), conducted at Moorfields Eye Hospital, London, compare favourably to outcomes seen in randomised clinical trials (Figures 1 and 2).

 Follow-up over 36 months further confirmed maintenance of vision long term with continued retreatment if needed.

At 3 years, eyes with worse visual acuity (VA) at baseline (<69 early treatment diabetic retinopathy study [ETDRS] letters), accounting for 58% of the study cohort, achieved greater than a two-line vision gain (+11.27 letters) from baseline, while stable vision was maintained in eyes having initially better VA (69–80 letters). Some 89% of patients overall received the recommended treatment initiation protocol of five consecutive monthly injections.

Lead author of both studies, Dr Marko Lukic, explained: “Clinical trials provide what I term the ideal results with respect to treatment efficacy and safety. Real-world studies provide us with more realistic results of treatment effectiveness in everyday practice using practical protocols.”

He added: “At month 36, one quarter of eyes gained at least three lines of vision from baseline and the final mean VA was around 69 ETDRS letters, meeting driving criteria.”

Overall, the mean VA gain was 9.9 letters with a mean of 6.9 injections over 12 months. The independent DRCR.net Protocol T study showed better improvements in VA with an average of nine injections in the first year.

 However, following strict protocols suggested by clinical trials is difficult to maintain in real-life settings, remarked Dr Lukic.

We mostly commence treatment of new patients with DMO using intravitreal aflibercept injections and always aim to provide five initial monthly injections and then treatment as needed, which for most patients means three bimonthly injections and an average of seven to eight injections in year one. It is important to secure the maximum vision improvement in the first year and, after that, to maintain stable vision with retreatment as needed.”

“We divided our study cohort into two subgroups according to baseline VA and showed that those with worse baseline VA (<69 letters, 20/50 or worse) had greater vision gains than those with better presenting vision. However, those with baseline VA ≥69 letters still achieved good maintained vision. And overall, when you compare these two subgroups, those who commenced treatment earlier (i.e., with better VA at baseline) had better results in terms of final VA letter score (approximately 75 vs. 63 letters, respectively, at month 36).”

If continuity of anti-vascular endothelial growth factor (VEGF) treatment for DMO is maintained and if there is no presence of significant macular ischaemia, then Dr Lukic believes good vision outcomes can be routinely achieved in everyday practice. Adherence to the initiation protocol of monthly loading followed by bimonthly injections in year one is extremely important, he said.

Dr Lukic added: “Diabetic macular oedema is a chronic condition and regular retreatment is needed for most patients. Retreatment beyond year one is led largely by optical coherence tomography appearance, i.e., those with persistent fluid or who develop new fluid continue to receive retreatment.”

“Some patients received more than three injections over both year two and year three. On the other hand, 13% of aflibercept-treated eyes received no further injections beyond the loading phase by the end of 3 years since initiation of treatment.”

There is always a small subgroup of patients who do not respond as expected and who may need to be switched to another treatment (e.g., 3/102 aflibercept-treated eyes in the cited 12-month study), Dr Lukic said. “Steroids may have a role in selected cases, for example, pseudophakic eyes with refractory or persistent DMO despite continued anti-VEGF therapy.” 

In a large real-word study in the United States, it was found that patients with DMO consistently achieved poorer vision outcomes and received fewer anti-VEGF injections than those in randomised clinical trials. A retrospective electronic medical record (EMR) database analysis of 28,658 treatment-naïve eyes treated with anti-VEGF for DMO from 2013 to 2018 found a mean VA gain of 4.2 letters with a mean of 6.4 injections over 1 year.

 This large sample of DMO patient eyes included all-comers who received at least one anti-VEGF injection and had 12-month follow-up data.

Half of all patient eyes received six or fewer injections over the year. Vision outcomes correlated with treatment intensity and, as expected, mean letter gains were higher in those with poorer starting vision. Outcomes similar to clinical trials were achieved in a subgroup of patients with moderately severe baseline visual impairment (20/70 to 20/200), showing a 1-year gain of 10.3 letters with ≥10 injections (from a mean baseline VA of 47.2 letters).

Commenting on the persistent reported gap between clinical trials and real-world outcomes, lead study investigator Dr Thomas A, Ciulla explained: “Our findings showing only limited vision improvement are attributed largely to two key factors: first, real-world patients differ from those in clinical trials and second, they are undertreated with a lower frequency of anti-VEGF injections.”

Patients with DMO can have chronic advanced oedema with ischaemia and atrophy, while some present with very good VA, Dr Ciulla said. “But even if real-world DMO patients differ from clinical trial participants, we should do everything we can for them: encourage them to comply with recommended treatment regimens and make sure they receive an appropriate level of treatment intensity.”

“Our data suggest that, to maximise real-world outcomes, the average DMO patient requires intense anti-VEGF therapy during the first year of treatment,” added Dr Ciulla. “Moreover, vision gains generally approach a plateau at a treatment frequency of nine or more injections in year one.” Slightly better overall outcomes were previously reported in another US EMR database study of DMO eyes that underwent ≥3 monthly anti-VEGF injections within 4 months of the first injection, where the mean 12-month visual improvement was 5.5 letters.

Importance of complete treatment initiation schedules

In France, a prospective cohort study (APOLLON) of aflibercept in private and public clinical practice showed improvements in functional and anatomical outcomes over 12 months in both treatment-naïve and previously treated patients with DMO (Figure 3).

The mean (SD) change in best-corrected visual acuity was +7.8 (12.3) letters in treatment-naïve patients and +5.0 (11.3) letters in previously treated patients at month 12, with patients receiving a mean of 7.6 injections, slightly lower than that in the aflibercept DMO registration trials. The proportions gaining 15 letters or more from baseline were 29.9% and 18.6%, respectively.

Of note, only 42.2% (n=62) of the study cohort received the complete five initial monthly doses as indicated in the label regimen. Table 1 shows visual outcomes stratified by initial treatment exposure in the treatment-naïve cohort, with better visual outcomes achieved in patients receiving the recommended treatment initiation schedule.

“Great steps forward have been made in the management of retinal disease in the past decade,” observed Dr Ciulla. “However, many of our current modalities require fixed, frequent treatments and what we ultimately need is better treatments that last longer.”


Dr Lukic is a locum consultant ophthalmologist, National Institute for Health Research (NIHR) Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. The research reported in this article was supported by the NIHR Biomedical Research Centre. He has no financial interests in the subject of this article.


Dr Ciulla is volunteer clinical professor of Ophthalmology at Indiana University School of Medicine, United States, a board member of Midwest Eye Institute, Indianapolis, and chief medical officer/chief development officer at Clearside Biomedical. Dr Ciulla has no financial interests in the subject of this article.

Lukic M, Williams G, Shalchi Z, et al. Intravitreal aflibercept for diabetic macular oedema: Moorfields' real-world 12-month visual acuity and anatomical outcomes. 

Lukic M, Gwyn Williams G, Shalchi Z, et al. Intravitreal aflibercept for diabetic macular oedema in real-world: 36-month visual acuity and anatomical outcomes. 

 19 May 2020. DOI:10.1177/1120672120925034.

The Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. 

Ciulla TA, Pollack JS, Williams DF. Visual acuity outcomes and anti-VEGF therapy intensity in diabetic macular edema: a real-world analysis of 28 658 patient eyes. 

. 7 Apr 2020. DOI: 10.1136/bjophthalmol-2020-315933.

Ciulla TA, Bracha P, Pollack J, Williams DF. Real-world outcomes of anti-vascular endothelial growth factor therapy in diabetic macular edema in the United States. 

Korobelnik JF, Daien V, Faure C, et al. Real-world outcomes following 12 months of intravitreal aflibercept monotherapy in patients with diabetic macular edema in France: results from the APOLLON study. 

Articles

Good early adherence to label regimens can make a difference, yielding vision outcomes approaching those in clinical trials, emerging real-world studies of anti-VEGF for DMO suggest. 

Emerging real-world evidence of anti-VEGF for diabetic macular oedema

Neodymium:yttrium aluminium-garnet (Nd:YAG) laser capsulotomy is a safe, effective, quick and relatively easy gold-standard outpatient procedure for the treatment for posterior capsule opacification (PCO) following cataract surgery. It improves visual acuity and may also have positive effects on glare and contrast sensitivity in some patients.

However, there are reports of complications associated with the method such as corneal injuries; pupil blockage; iritis; increases in intraocular pressure (IOP); vitreous prolapse; retinal damage; and luxation/decentration of the IOL or damage to the IOL material (pitting). Pitting occurs in 15–33% of eyes during Nd:YAG laser posterior capsulotomy.

In the past, incorrect and inaccurate focusing of the laser beam was identified as the main cause of pitting. In several cases, time pressure could be determined as the main cause for these iatrogenic defects. Pitting is supposedly not visually signiﬁcant, although rarely the damage may cause sufﬁcient glare, straylight and image degradation to require the damaged IOL to be explanted (Figures 1–2).

The two primary YAG techniques are the cruciate pattern and the circular pattern, and each has its benefits and downsides. In the cruciate method, the YAG laser is used to create a cross pattern, which then allows the resultant capsule flaps to retract out of the visual axis.

Laser spots are placed through the centre of the IOL. Therefore, care must be taken to properly aim the laser to avoid pitting the optic in the central visual axis.

The circular technique creates a circular cutout, which then allows for a round posterior capsular opening. With this method, laser shots do not need to be placed in the central optical zone but in the periphery.

Thus, the chance of central pitting and negative effects on the optics is lower. Some data also found that the frequency of IOL damage depends on the IOL design.

A design separating the posterior capsule from the IOL (ridge) is less prone to damage than lenses with a close apposition between the IOL posterior surface and the posterior capsule. Current attempts to reduce or prevent PCO by having posterior capsule adhesion to the IOL might complicate laser treatment and increase rates of damage in the future.

Nd:YAG rates commonly reported before 1992 were between 20% and 33%, while Nd:YAG rates for IOLs implanted 10 years later were below 17%. In the past, numerous studies on various IOLs showed very different, unsteady results of Nd:YAG and PCO rates (5–2%) 3–5 years after surgery.

We recently conducted a study to assess differences in Nd:YAG-induced defects between hydrophilic and hydrophobic IOLs and describe optical and surface properties. The main aim was to increase awareness of the need to approach Nd:YAG laser capsulotomy with a greater level of caution. We recognised that hydrophilic and hydrophobic IOL materials seemed to be affected differently by Nd:YAG treatment according to wavefront aberrations and in slit lamp examinations.

A total of 12 different monofocal IOLs from nine manufacturers were evaluated. All five hydrophilic lenses had a refractive index of 1.46 and a water content of 26%. Of the seven hydrophobic IOLs, two were yellow and one had an additional heparin coating.

Refractive index varied between 1.47 and 1.55 and the water content was less than 1% except for one lens which was 4% water. All lenses were manufactured with a 360° sharp edge and had a spherical power of 21.5 dioptres.

Reflected-light microscopy and an environmental scanning electron microscope (ESEM) were used to visually analyse the defects. Additionally, wavefront measurements were taken for exact power mapping of the IOL optic and Raman spectroscopy was performed. Vertical and horizontal dimensions of the defects were analysed and compared, and Raman line scans assessed the chemical changes in the defect area and surrounding area.

In photomicrographs of the hydrophilic and hydrophobic IOLs after laser treatment, pits created by the laser were observed on both types of materials. The damage appeared to be bigger and more intense within the hydrophobic lenses than in hydrophilic ones. In the hydrophobic lenses the pits looked similar to the branches that appear when glass breaks and could be seen even with less magnification, while in the hydrophilic ones, they were not as visible.

These smaller zones of damage appeared like bullet holes with a smoother rim. An additional observation was that shots made directly next to already existing defects produced larger craters. This could be caused by a change in the material surrounding the defect (surrounding area).

The ESEM images confirmed the results and showed deeper and greater damage in hydrophobic materials than in hydrophilic. Damage to hydrophilic lenses seemed to be more circular while those in hydrophobics were more frayed (Figure 3).

In Raman spectroscopy, defects were found to have different depths, with deeper pits seen in hydrophobic lenses (Figures 4–5). Raman line scans showed the area of defect in terms of chemical changes. These areas were found to be bigger than the visible defect area and, again, this effect was greater in hydrophobic lenses.

Regarding the level to which the optical properties of the IOL changed after the treatment, a difference was noted within each group but it was not a significant one. Wavefront analysis revealed unusual white spots, besides the well-known colour map of the power of the lens. These spots occur when an area of the sensor has not been illuminated, since the light beam deflection at a defined point of the lens is so large that it no longer falls into the corresponding microlens, as in the case of damage and material defects.

Our results may support the assumption that the differences between the materials are mainly due to the differing water content. Defects can be seen very well even within standard slit lamp examination.

We also found evidence that the material at the point of entry (area of the shot) and surrounding area changes chemically due to the procedure. These changes seem to be greater than what is visually observable.

If we analyse a hydrophobic lens as an example, the visible damage was measured at 81 µm (vertical) and 95 µm (horizontal), however, the chemical changes increased these to 120 µm (vertical) and 124 µm (horizontal), which was an enlargement of 48% and 31%, respectively. This means that the area of the defect in the IOL was not 7,600 µm² (visible area) but 14,800 µm² (actual area), which meant it was twice as large.

Despite modern, high-quality measurement methods, such as wavefront and other advanced technologies, it is currently difficult to measure just a small area. If, on the other hand, larger apertures and measuring areas with a diameter of 4, 5 or 6 mm are used, changes are still visible but no longer significant.

Nevertheless, it seems logical that the position of the defect plays a decisive role; if it is located centrally in the visual axis (pupil centre), the effects are greater than if it is located peripherally. Moreover, the IOL type and model plays another important role; it can be assumed that pitting in IOLs with bifocal, trifocal or enhanced depth of focus design lead more easily to clinically significant optical phenomena than in monofocal IOLs.

The results of this study support clinical experience and show that iatrogenic-induced YAG shots in IOLs behave similarly to other defects and clouding/haze in such lenses, such as scratches (after improper folding of the IOL or incorrect manipulation with a spatula or forceps), glistenings or calcification in IOLs.

In all cases, the extent and severity as well as the position/area in the IOL optic is most important. When it comes to clinical symptoms, there is a wide variability, ranging from no effects or mild symptoms to severe clinically significant effects on the overall quality of vision.

Concluding thoughts and future perspectives

Ophthalmologists should be as cautious as possible when performing laser capsulotomy. In the worst-case scenario, an improper YAG-procedure can lead to major clinical effects and permanently influence the optical quality.

For such patients, explant of the IOL may need to be considered, but this has a further risk of complications. Therefore, it is important that patients are informed about all the potential dangers before they undergo a supposedly short and simple YAG procedure, and that the doctor is aware that these tiny defects could actually have a greater impact than is often thought.

Ophthalmologists should also consider the position of YAG laser. Laser shots do not need to be placed in the central optical zone but in the periphery, so the chance of central pitting and negative effects on the optic is lower. Moreover, the procedure should not be performed under time pressure.

If for any reason the lens is bombarded and defects do occur, the doctor should halt the procedure immediately. To continue operating would be irresponsible and could amount to an ‘ophthalmic terrorist attack’, which will certainly have clinical implications.

studies is needed. Additional aids could be developed by companies to further minimise the risk. For example, an acoustic signal could be used to draw attention to a patient’s head movements or warn that the focus of the laser beam is incorrectly adjusted. In addition, an ocular measuring device would help to avoid pitting the central, and most important, area of the lens and at the same time achieve a sufficiently large capsulotomy.

Andreas F. Borkenstein, MD and Eva-Maria Borkenstein, MD


Drs Borkenstein & Borkenstein are based at a private practice in the Privatklinik der Kreuzschwestern, Graz, Austria. They have no financial disclosures to reveal.


Borkenstein AF, Borkenstein EM. Analysis of YAG-Laser induced damage in intraocular lenses: characterization of optical and surface properties of YAG-shots. 

Poorly focused YAG shots lead irrevocably to a permanent defect in the IOL material and thus to possible effects on the quality of vision with straylight or glare. In a recent study, the differing amounts of damage that Nd:YAG causes in a range of hydrophilic and hydrophobic acrylic lens materials was assessed.

YAG-shots in IOLs: Safe or dangerous?

Optical coherence tomography angiography (OCT-A) is an evolving multimodal imaging modality with some barriers to its widespread usage and implementation in retina practices, most of which are related to its financial burden, for example, the cost and reimbursement. Another limiting factor is that many retina physicians are not trained to interpret the data and images that OCT-A produces.

Standardised criteria and guidelines should be defined in order to help retinal physicians interpret the scans. As a specialist in retina and vitreous diseases, I have had the unique opportunity to use this non-invasive imaging technique for regular diagnosis, management and follow up of retina patients in my practice. Herein, I will share my ‘real-world’ experience of using OCT-A daily in three main areas of macular disease: age-related macular degeneration (AMD), central serous retinopathy and other pachychoroidal cases.

Commercially available OCT-As are either spectral domain (SD) OCT-As—which include the Angioplex OCT-A (Carl Zeiss), the AngioVue OCT-A (Optovue) and the Spectralis OCT-A Module with TruTrack (Heidelberg Engineering)—or swept-source (SS) OCT-A, which are the Plex Elite OCT-A (Carl Zeiss) and DRI OCT Triton (Topcon). An SS-OCT-A has a centre wavelength of approximately 1,060 nm compared with SD OCT-A, which is approximately 840 nm. SS-OCTA provides a higher scanning speed of 100,000 to 200,000 A-scans/second that is coupled with a longer wavelength and less sensitivity roll-off, hence denser, wider, deeper and faster scans can be obtained.

OCT-A can demonstrate layer-specific flow and structural information that is not possible with dye-based imaging. Recent research has shown that the technique provides good visualisation of the neovascular network, choriocapillaris and choroid compared with fluorescein angiography (FA) and indocyanine green angiography (ICGA).

OCT-A can provide information about the presence or absence of choroidal neovascularisation (CNV) when other dye-based studies may be inconclusive due to blockage from subretinal haemorrhage or non-specific diffuse staining patterns.

OCT-A is also helpful for positively identifying a neovascular network and differentiating vascular from avascular components in subretinal hyper-reflective material or vitelliform cases seen in macular diseases.

I primarily use OCT-A (AngioPlex) for tracking and diagnosing AMD, assessing choroidal neovascularisation and determining whether a patient has wet or dry AMD or central serous retinopathy. If I examine an eye that reveals the presence of fluid on standard OCT but I am not entirely sure that there is a neovascular process, I obtain an OCT-A scan to verify the presence of fluid. The results help to guide my treatment choices.

Another benefit of using OCT-A is to investigate what is traditionally called dry macular degeneration, where we do not see any exudation on OCT but we do see something on OCT-A, which Dr Philip J. Rosenfeld refers to as the double-layer sign. This means that there is a low-lying pigment epithelial detachment, which has vascularised. I like to refer to it as neovascular non-exudative AMD.

Abnormal ICGA findings, such as focal hot spots or plaques, were previously detected in these eyes but angiography could not be justified as a screening tool due to increased costs and risks. However, with access to OCT-A imaging, I can assess a neovascular process and diagnose and follow these patients accordingly. Even though I may not treat them with anti-vascular endothelial growth factor drugs, OCT-A results help me to alter my follow-up algorithm so that I monitor those patients every 8–12 weeks, which is more closely than normal because they have a higher likelihood of developing exudative macular degeneration over the course of time as demonstrated in natural history studies.

It is very important to understand your individual machine and recognise that image interpretation is a dynamic process that may require direct interaction with the OCT-A device. It is also important to choose the correct segmentation slab to obtain the right information from the OCT-A image.

I usually obtain 3x3 and 6x6 scans of the macula. The scan segments the superficial retina, the deep retina, the choroid and the choriocapillaris, and I create a custom slab retinal pigment epithelium (RPE) to RPE-fit (Bruch’s membrane) to detect type 1 CNVs.

It is also important to critically analyse the OCT-A images and exclude the possibility that the presumed CNV flow may be a projection artifact arising from the retinal vasculature or due to hyper-transmission defects arising from an attenuated or absent RPE.

 The software algorithms continue to improve, but sometimes they make segmentation errors, such as in cases with large pigment epithelial detachments (PEDs).

In these cases, I recommend the user manually segments these layers to obtain an accurate representation of the PED. Therefore, it is important to be familiar with how to create segmentation slabs that enable the parameters that the machine provides to be manipulated in order to adequately analyse the OCT-A images.

As we look towards the future and as OCT-A and, more specifically, SS-OCTA technology evolves, we will be able to obtain wide-field and montage images that will provide us with greater insight into the pathophysiology and management of diabetic retinopathy and allow earlier identification of pathologic changes. With time, as the devices become faster, the algorithms advance and the instrument costs decrease, I expect more widespread utilisation of OCT-A in retina practices.


Dr Fortun is an associate professor of clinical ophthalmology and medical director of Bascom Palmer Eye Institute at Palm Beach Gardens, University of Miami, Florida, United States. Dr Fortun is a consultant for Carl Zeiss Meditec.

Cicinelli MV, Cavalleri M, Consorte AC, et al. Swept-source and spectral domain optical coherence tomography angiography versus dye angiography in the measurement of type 1 neovascularization. 

Jia Y, Bailey ST, Wilson DJ, et al. Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration. 

Zhang Q, Chen CL, Chu Z, et al. Automated quantitation of choroidal neovascularization: a comparison study between spectral-domain and swept-source oct angiograms. 

Novais EA, Adhi M, Moult EM, et al. Choroidal neovascularization analyzed on ultrahigh-speed swept-source optical coherence tomography angiography compared to spectral-domain optical coherence tomography angiography. 

de Oliveira Dias JR, Zhang Q, Garcia JMB, et al. Natural history of subclinical neovascularization in nonexudative age-related macular degeneration using swept-source oct angiography. 

Yang J, Zhang Q, Motulsky EH, et al. Two-year risk of exudation in eyes with no exudative and subclinical neovascularization detected with swept source oct angiography. 

As OCT-A devices become faster, the algorithms advance and the instrument costs decrease, more widespread utilisation in retina practices is likely.

Real-world experience of OCT-A for retinal diagnoses and management

Adequate visualisation of the lens is necessary for safe cataract surgery, and the best way to achieve this is with dilated pupils. Inadequate pupil dilation can lead to surgical complications including iris damage, bleeding, prolapse, intraoperative floppy iris syndrome (IFIS), anterior capsule trauma and misalignment of the IOL. All of these are best avoided by ensuring you have a wide pupil.

Current approaches to small pupil management include cutting the iris at its edge, stretching the pupil mechanically using two side instruments, the use of iris hooks, heavy viscoelastic application and pharmacological dilation, or pupil expansion devices such as the Malyugin ring 2.0 (MicroSurgical Technology).

This is an innovative device that was initially designed by Prof. Boris Malyugin to expand the small pupil safely and effectively as a solution to the potential overstretching of the iris sphincter or extended surgery time.

 I think the Malyugin ring is one of the best tools to dilate the pupil and maintain that dilation intraoperatively, therefore streamlining even the more challenging cataract cases.

The ring is manufactured with 5.0 polypropylene, which is a thin (<1.0-mm) and flexible material. This makes it elastic, so it causes less damage to the iris compared with other devices. It also features a large scroll gap that eases the engagement of the iris and removal of the ring.

I use both sizes of the Malyugin ring, 6.25 mm and 7.0 mm, depending on the diameter of the eye and the individual pupil. Sometimes the anterior segment is small, especially in hyperopic eyes, in which case it would be difficult to insert the larger size. In myopic eyes, I tend to use the bigger size.

The size chosen will also depend on the thickness of the iris as some can be stiff, especially in post-traumatic eyes, and it can be challenging to place the eyelets precisely in the iris. So, it depends on the situation and the individual case.

There are essentially two main cases where I use the Malyugin ring 2.0 in surgery. One is when there is a small pupil with no synechiae. Small pupils with no synechiae can result from alpha-blocker treatment, IFIS or other conditions. In cases of small pupils with synechiae, it is necessary to release all adherences between the iris and the lens before placing the device.

Other cases where I use the ring often include an exchange to a posterior lens due to subluxation. In these cases, I aim to keep the pupil dilated to see precisely where the lens and the bag are in the posterior segment of the eye.

: IFIS can complicate cataract surgery and can frequently occur in patients taking alpha-blocker medications such as tamsulosin (Flomax, Astellas). Physicians often prescribe alpha-blockers for the treatment of benign prostatic hyperplasia, to women with urological issues and patients with hypertension.

At first, I use a pharmacological product such as adrenaline to dilate the pupil. If working under topical anaesthetic, I advise adding non-preserved 1% lidocaine, resulting in intracameral anaesthesia, and adding modest dilation by paralysing the nerves in the iris. Currently, my preference for pharmacological dilation is Mydrane (tropicamide 0.2 mg/mL, phenylephrine chlorhydrate 3.1 mg/mL, lidocaine chlorhydrate 10 mg/mL; Thea).

Synechiae need to be released before inserting the Malyugin ring. First, one should break the posterior synechiae with a cyclodialysis spatula or cannula. I like to use a blunt cannula; for instance, a LASIK cannula. Ensuring all the synechiae are released is of paramount importance as I do not want any remaining under the iris.

Mechanical dilation follows. In this step, I will simply stretch the small pupil using a Lester hook and capsulorhexis forceps. This bi-manual technique allows me to dilate linearly and then at a 90-degree angle.

Before inserting the ring, I add more viscoelastic device into the eye to lift the iris from the anterior capsule. The device comes with an injector for easy insertion and removal and is specifically designed to be implanted through a 2.0-mm incision.

I normally insert the Malyugin ring injector upside down through the incision with the footplate on top. This allows me to get closer to the iris with the injector to engage the first three scrolls of the ring as it is released from the injector (Figure 1).

To remove the ring, I disengage the scrolls to lift it above the iris plane. Again, I use the injector upside down; I grasp the proximal scroll with the injector hook and the ring is retracted using a sliding mechanism. Insertion of the ring requires the skill of the surgeon, a skill that comes with experience using the device.

The Malyugin ring 2.0 is, for me, the pupil expander of choice: it exhibits precision, is easier to use than iris hooks,

 has a good safety record and allows excellent intraoperative visualisation. It essentially changes complicated cataract surgery into a routine procedure.

Dr Rozot is an ophthalmic surgeon based in Marseille, France. He specialises in refractive cataract surgery, management of complex cataract cases, such as post-traumatic or congenital, and surgical treatment of glaucoma. He has no financial interest in the subject of the article.

Malyugin B. MicroSurgical Technology: The new generation of the Malyugin Ring 2.0. Available at: https://www.youtube.com/watch?v=8_5qWnBDxNg.

Nderitu P, Ursell P. Iris hooks versus a pupil expansion ring: Operating times, complications, and visual acuity outcomes in small pupil cases. 

The Malyugin ring 2.0 expands the small pupil safely and effectively to enable excellent intraoperative visualisation. It has a good safety record and is easier to use than alternative methods.

Managing small pupil challenges in patients with the Malyugin ring  

Overview of diabetic eye disease

Imaging for diabetic retinopathy

Use of OCT-A for patients with diabetes

Optimizing diabetes health management

Diabetes management: Communication between ODs and MDs

Challenges to diabetes management

ADA guidelines for DR/DME management

Treatment options for DR/DME

Emerging agents for the treatment of DR/DME


A panel of experts in ophthalmology and optometry review the diagnosis and treatment of diabetic eye disease including emerging agents in the field.

Updates on diabetic macular edema and diabetic retinopathy  


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 

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.

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

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

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

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

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.

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.

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.

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.

 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 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.

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.

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.

 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

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.

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.

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.

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.

‘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.

 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.


Prof. Augustin declares that he recieves advisor and speakers honoraria with Allergan and Alimera.


Prof. Baudouin declares interests with Aerie, Alcon, Allergan, Horus Pharma, Santen and Thea.


Prof. Faschinger declares no financial interests.


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


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

In this roundtable, members of the Ophthalmology Times Europe® Editorial Advisory Board consider the top challenges and opportunities that they anticipate will affect ophthalmology in Europe in 2021.

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



Robert Weinstock, MD, director of Cataract & Refractive Surgery, The Eye Institute of West Florida; the Weinstock Laser Eye Center, presents real-world data from a retrospective multicenter study focusing on the efficacy of dexamethasone intraocular suspension 9% delivered at the time of cataract surgery.

Weinstock notes that research shows the injections can decrease inflammation and control IOP.

Robert Weinstock, MD, presents data from a retrospective multicenter study focusing on the efficacy of dexamethasone intraocular suspension 9% delivered at the time of cataract surgery. 


AAO: Study outlines use of injectable intraocular steroid over drops

Physicians at Kaiser Permanente have been using a prophylactic drop-free drug regimen before cataract surgery for more than a decade. 

Their regimen is so streamlined that the only drop that patients receive in anticipation of cataract surgery is a supplemental dilation drop instilled preoperatively while they are still in the holding area, according to Neal H. Shorstein, MD, who discussed the topic at the American Academy of Ophthalmology’s virtual 2020 annual meeting.

Dr. Shorstein is an ophthalmologist, researcher and associate chief of quality at Kaiser Permanente Medical Center in Walnut Creek, CA.

This more efficient approach seems highly beneficial for patients because drop instillation is associated with a few risks, i.e., prescription error, failure to pick up the prescription, failure to adhere to the instillation instructions, and stopping the drops prematurely. 

If only the correct instillation is considered, 93% of drop-naive patients have been reported to instill drops incorrectly. In addition, the bottle tip can become contaminated and it can cause microtrauma. 

The resistance of bacteria to topical antibiotics is another issue, such that instillation periods that are too short or too long or repeated over time can result in bacterial resistance. Finally, and not to be overlooked, the drugs can be expensive.

During AAO 2020, Neal H. Shorstein, MD, explains how physicians at Kaiser Permanente have a streamlined regimen using a prophylactic drop-free drug before cataract surgery for more than a decade. 