This is the third in a series of articles that summarises an afternoon of presentations, plus a debate, on the topic of corneal ectasia that was held as part of the recent 29th Cologne Adventsymposium, an annual meeting organised by Laserforum e.V., in Cologne, Germany. Chaired by Drs Omid Kermani and Georg Gerten, the presentations each considered the condition from a different perspective and are available 

Part 1, published in the June 2022 issue of 

considered the contribution of eye rubbing to the development of keratoconus

. Part 2, published in the July/August 2022 issue, 

looked at developments in diagnostics and classification methods for ectatic corneal diseases

. This third part of the series covers epithelial imaging and is based on the presentation by Prof. Dan Reinstein and Dr Tim Archer.

Reviewed by Dr Omid Kermani, Prof. Dan Reinstein and Dr Tim Archer.

Prof. Reinstein began his talk by introducing the concept of the epithelial thickness profile, explaining that he had been the first to publish 10-mm epithelial thickness maps of the normal virgin cornea with 1 µm precision.

 As expected, he found the central thickness to be around 50 µm but, going against everything that had been published previously, found that the epithelium does not have an even profile, being an average of 6 µm thinner superiorly than inferiorly and about 1 µm thicker nasally than temporally. Right and left eyes have mirror asymmetry.

His group has now published around 40 papers on the epithelium alone. “OCT is now confirming many of the things that we discovered originally with ultrasound,” he explained. “What we have learned is that the epithelium changes in all situations where you change the stromal surface curvature.”

According to Prof. Reinstein, looking at how the epithelium behaves in different situations allows four basic rules to be written on how the epithelium acts and how it remodels after a stromal surface change, as follows.

The epithelium thickens to fill any relative depressions.

The epithelium thins over relative peaks within the stroma.

The change in the epithelium is proportional to the change in the stroma. Higher myopicablation produces more central epithelial thickening and peripheral thinning;

 higher hyperopic ablation produces more peripheral epithelial thickening and central thinning.

 Epithelial changes are more marked the more severe the keratoconus.

The amount of change is defined by the rate of change of curvature (or curvature gradient). For example, a depression from a corneal ulcer that is 1-mm wide and 200-µm deep will be almost entirely smoothed by the epithelium, but a 4.5-mm zone depression made in the stroma by PRK is compensated for less. This corresponds with the improvement in refractive stability and reduction in regression when using larger optical zones.

The cornea has a front (stromal) surface and a back surface. In keratoconus, the front and back surfaces extrude and the epithelium remodels over the peak to become thinner, but it also becomes thicker around the peak to form a “doughnut” shape. As Prof. Reinstein explained, interestingly, when you have a very mild back surface extrusion yoked to a very mild front surface extrusion, the epithelium is able to fully compensate.

This leads to focal thinning of the epithelium in a doughnut pattern overlying the back surface elevation, which is eccentric. The front and back surface data alone may get lost in the soup of statistical variation and therefore fail to signal keratoconus with enough sensitivity.

Commercially, what has become of interest, and what spawned the OCT epithelial thickness industry, was Prof. Reinstein’s demonstration that you could have inferior steepening that could be confirmed by an epithelial thickness map not to be keratoconic but rather due to a thicker inferior epithelium.

His study of 1,500 eyes demonstrated that mapping the epithelium allowed exclusion of keratoconus in 84% of these highly equivocal back surface elevation abnormalities.

 This then led to an increase in patients eligible for excimer laser surgery.

Having studied the epithelial thickness profile in keratoconus and established that the more advanced the keratoconus, the thinner the epithelium becomes over the cone and the thicker it becomes around the doughnut, Prof. Reinstein then sought to try and parameterise how this difference in epithelial modelling could be exploited in the very mildest keratoconic cases.

In one of the earliest machine-based pattern-recognition studies from topographic maps,

 Prof. Reinstein’s researchers set up around 160 variables in epithelial profiles that they thought might be relevant with respect to keratoconus screening, only six of which turned out to be relevant. This provided an automated algorithm with exceedingly high specificity and sensitivity for keratoconus. It detects a 1- or 2-µm change in epithelial thickness profile, which is much more sensitive than the 1- or 2-µm elevation detected by a topographic or tomographic device with back surface mapping.

Prof. Reinstein explained that the epithelial thickness profile can be used as an adjunctive tool in cases of suspected keratoconus and has applications in cases with seemingly normal topography, cases where both topography and tomography are suspect, and most importantly, those that have normal topography and normal tomography.

 shows a case with normal front surface topography, normal Belin/Ambrósio and BAD-D (Belin/Ambrósio display, D value) and nothing remarkable between the back and front surfaces. The epithelial thickness profile shows quite significant focal thinning in the centre of the cornea and the pattern deviation map also shows inferior thinning in an unexpected location.

The Reinstein-Silverman-Keratoconus (RSK) score in this case implies a definitive keratoconus diagnosis.

Prof. Reinstein said, “The point is that keratoconus can be detected with high sensitivity. This avoids false negatives when screening for keratoconus using only topography by proving that the epithelial thickness profile has the doughnut configuration. [It also avoids] false positives in cases that machine algorithms classify as keratoconic … but use of an epithelial profile shows a thicker epithelium over the zone where there is increased steepening.”

Prof. Reinstein explained that the epithelium is a dynamic layer that changes easily with all kinds of conditions and therefore contact lens warpage, anterior basement membrane dystrophy, tear film abnormalities, meibomian gland dysfunction, dry eye and eyelid forces can lead to epithelial redistribution. 

 illustrates a cornea that (left) has been out of a soft contact lens for 3 days and appears very keratoconic and then (right) looks less keratoconic after 2 weeks; the difference is epithelial remodelling.

Anterior basement membrane dystrophy (ABMD) produces a very abnormal epithelial profile with duplication of the basement membrane and, therefore, thickening of the epithelium. 

 shows an example of the epithelial profile showing doughnut-shaped thinning, which might well be mistakenly interpreted as being keratoconus but is actually ABMD.

As a way of indirectly proving that it is the eyelid forces that cause epithelial thickness changes, 

 shows a patient with a Bell’s palsy, who does not blink very much with one of his eyes. The epithelium is thickened significantly in that eye, producing a myopic shift, whereas the epithelial thickness profile is much more even in the eye that blinks normally.

Thus, performing refractive surgery without epithelial maps, when there are multiple commercially available devices to provide such a map, seems unwise. Instead of relying entirely on machine learning, it is better to use one’s clinical skills in order to screen for keratoconus.

Following Prof. Reinstein’s presentation, Dr Archer debated its content with the other presenters—Dr Kermani (Germany), Prof. Damien Gatinel (France), Prof. Renato Ambrósio Jr. (Brazil) and Prof. Farhad Hafezi (Switzerland). The responses in italics below were not given at the time, because of time constraints, but have been provided during the review process.

Epithelial mapping seems to be a very important step in diagnosis in both keratoconus and ectasia. Do you use high-speed ultrasound or OCT?

 There are variety of machines on the market to map the epithelium. Most of the maps we showed in this presentation were from the ArcScan Insight 100 very-high-frequency digital ultrasound device but we also showed quite a few maps from the MS-39 OCT device, so yes, we use both systems.

 If you look at epithelial mapping from a clinical perspective, if the epithelium is so delicate, would that be a reason not to do topo-guided LASIK? Or is that a procedure in which the epithelium already masks the effect of whatever we do to the stroma?

Most topography-guided systems derive the ablation algorithm using the front surface topography, which means that it will be less accurate in eyes with an irregular epithelium. Most patients have a reasonably regular epithelium but some do not. In eyes with an irregularity on the epithelium, this will throw off the topography-guided algorithm and you may end up with an outlier.

If you have a global irregularity, like a decentration or a small optical zone, the epithelial remodelling is more global; most of the irregularities show through on the topography and topography-guided treatment works very well.

If you have localised irregularities, there is a lot more epithelial remodelling, which masks the defect, and so topography measurements cannot see the actual shape of the stroma. In this case, topography-guided treatments do not work very well and can actually make things worse.

The link between epithelial thickness and topography is very important. Topography-guided treatments should not be done without first measuring the epithelial thickness and ensuring that it is reasonably regular.

 Damien, what is your opinion on epithelial mapping? Is it so sensitive and helpful in our daily diagnosis that we really need to add it to our multi-modality diagnostics? Do you use it?

 My view is that I have not yet seen a patient for whom the epithelium was altered from what you expect in a normal patient, yet the cornea was not deformed on the anterior or posterior surface. I do not believe that there is a primitive deformation of the epithelium. As eye rubbing is exerted directly on the epithelium, you may expect to see some deformation, but it is not clinically obvious.

Of course, when you have keratoconus you have a specific pattern, which usually shows as a regularisation pattern. What I find fascinating is how the epithelium remodels itself. If I were involved in epithelial research I would hire a real surface scientist or a physicist or mathematician specialised in those things to understand what drives the epithelium to remodel itself. I know we blink 10,000 times a day but still, how does this work?

The epithelium feels the defects but it is fascinating that it remodels, probably in response to both biological and physical elements like surface tension. When you put a drop of water on a surface it takes a shape that depends on the hydrophilicity or hydrophobicity of the surface but also obeys physical laws. The epithelium probably obeys the same laws but I would love to see some research in that direction.

It is good that the epithelium regularises the cornea, but how much and how can we predict it? This is really fascinating to me. In refractive surgery, if you could predict how the epithelium would react to a specific profile of ablation you could maybe anticipate it and correct for it.

 We agree with Prof. Gatinel that there would not be epithelial thickness changes in an eye with keratoconus without a deformation of at least the posterior surface. However, the point that we are making is that the epithelial thickness profile is used as an adjunctive tool to confirm or exclude keratoconus in eyes with equivocal changes on tomography.

In general, keratoconus screening is improved with the addition of further measurement modalities. Epithelial thickness mapping and Corvis biomechanical measurements are two examples of how keratoconus screening can be improved beyond topography and tomography alone.

 Kanellopoulos and Kahn performed hyperopic LASIK in combination with cross-linking and showed that the results are more stable with regard to regression and stability than without cross-linking,

 so your point is valuable and we should look into this.

 We do not agree with this statement. The Kanellopoulos study is interesting; however, the population included only 34 patients so the results have a very low statistical power and have not been replicated to date. As a comparison, our published results for hyperopic LASIK using the MEL 90 demonstrated better stability than the group that included cross-linking in the Kanellopoulos study.

The pathophysiology and pathomorphology of corneal ectasia: 

Dan Reinstein, MD, MA (Cantab), FRCSC, DABO, FRCOphth, FEBO

Timothy Archer, MA (Oxon) DipCompSci (Cantab) PhD

Prof. Reinstein is the medical director of the London Vision Clinic and holds professorships at Ulster University (Coleraine, UK), Columbia University (NY, USA) and the Sorbonne University (Paris, France). Prof. Reinstein is a consultant for Carl Zeiss Meditec (Jena, Germany) and CSO Italia (Florence, Italy) and acknowledges a financial interest in Artemis Insight 100 VHF digital ultrasound (ArcScan Inc.).

Dr Archer has been the research manager at London Vision Clinic since 2003. Dr Archer has no financial interest regarding the topic of the article.

Dr Kermani is specialised in cataract and refractive surgery and has worked in private practice since 1993. He is based at the Augenklinik am Neumarkt in Cologne. He has no financial interest regarding the topic of the article.

1. Reinstein DZ, Archer TJ, Gobbe M, et al. Epithelial thickness in the normal cornea: three-dimensional display with Artemis very high-frequency digital ultrasound. 

2. Reinstein DZ, Archer TJ, Gobbe M. Change in epithelial thickness profile 24 hours and longitudinally for 1 year after myopic LASIK: three-dimensional display with Artemis very high-frequency digital ultrasound.

3. Reinstein DZ, Archer TJ, Gobbe M, et al. Epithelial thickness after hyperopic LASIK: three-dimensional display with Artemis very high-frequency digital ultrasound. 

4. Reinstein DZ, Gobbe M, Archer TJ, et al. Epithelial, stromal, and total corneal thickness in keratoconus: three-dimensional display with Artemis very-high frequency digital ultrasound. 

5. O’Brart DP, Corbett MC, Verma S, et al. Effects of ablation diameter, depth, and edge contour on the outcome of photorefractive keratectomy. 

6. O’Brart DP, Gartry DS, Lohmann CP, et al. Excimer laser photorefractive keratectomy for myopia: comparison of 4.00- and 5.00-millimeter ablation zones.

7. Reinstein DZ, Archer TJ, Gobbe M. Corneal epithelial thickness profile in the diagnosis of keratoconus. 

8. Reinstein DZ, Archer TJ, Gobbe M. Stability of LASIK in topographically suspect keratoconus confirmed non-keratoconic by Artemis VHF digital ultrasound epithelial thickness mapping: 1-year follow-up. 

9. Silverman RH, Urs R, Roychoudhury A, et al. Epithelial remodeling as basis for machine-based identification of keratoconus. 

10. Kanellopoulos AJ, Kahn J. Topography-guided hyperopic LASIK with and without high irradiance collagen cross-linking: initial comparative clinical findings in a contralateral eye study of 34 consecutive patients. 

11. Reinstein DZ, Carp GI, Archer TJ, et al. Outcomes for hyperopic LASIK with the MEL 90® excimer laser. 

Articles

The epithelium adapts to compensate for changes in the cornea and these changes can be detected with high sensitivity, reducing both false positives and false negatives in the diagnosis of keratoconus.

Corneal ectasia part 3: OCT epithelial thickness measurements allow monitoring of corneal changes

Great strides have been made in recognising and treating keratoconus. Recent imaging technologies, such as optical coherence tomography, have identified thinning of corneal tissue over the cone, and wave-front aberrometry shows higher-order aberrations that may facilitate the diagnosis.

Yet the pathway to diagnosing the condition is not always free of roadblocks, according to Dr Sumit Garg, professor of cataract, corneal and refractive surgery at the Gavin Herbert Eye Institute, University of California, Irvine, California, United States. Dr Garg said that keratoconus has two components: genetic and environmental. The latter, he said, includes allergies and eye rubbing (during waking and sleeping hours), which is a huge driver of keratoconus progression. If eye rubbing persists, progression can occur despite cross-linking treatment.

Dr Garg also pointed out that the diagnosis can depend on where a patient lives and their genetic make-up. “The keratoconus prevalence is individualised and [keratoconus] can be prevalent in up to 5% of particular populations as shown in a recent study,” he said.

 With the rapid advancements in this field, the next step is determining the role of genetic testing in this patient population.

Genetic testing in patients at risk of keratoconus is in its infancy. Dr Garg reported that AvaGen75 (Avellino) is a test—the first of its kind— that looks at variants of genes reported to be associated with keratoconus. “The test, which looks at 75 genes and more than 2,000 variants, provides a scale ranging from 0 to 100 that defines the genetic risk of a patient developing keratoconus,” Dr Garg said.

The manufacturer reports that the test provides a risk score from data based on multiple gene clusters that have a high correlation with keratoconus, with the goal of providing an early diagnosis. Dr Garg emphasised that keratoconus is polygenic and not binary (i.e., the presence of genes does not necessarily mean that a patient has clinical evidence of keratoconus). He also cited a study

 that found that when genetic testing is coupled with advanced imaging, the chances of identifying keratoconus early are greater.

In his practice, he is offering genetic testing as an option, especially when there is a suspicion of keratoconus. Those who request a refractive surgery and those with family members who have been diagnosed with keratoconus are also offered testing.

Representative results of genetic testing

Dr Garg reported the case of a woman aged 32 years, who was referred for an ocular evaluation for a possible LASIK procedure. The patient was highly myopic with high cylinder, but her vision had been stable. The best-corrected vision was 20/20 bilaterally; she denied eye rubbing.

The topography maps indicated possible posterior changes, with some steepening in the corneal centre, and changes on the ABCD score. The Kmax values were generally thin overall. The patient had no family history of keratoconus.

Genetic testing showed moderate-to-high risk of keratoconus. The decision was made not to perform the refractive procedure and to perform a follow-up examination in 6 months. If the changes were progressive, corneal cross-linking could be considered. If follow-up showed no progression, an implantable collamer lens could be considered.

A second case was that of a woman aged 31 years, who presented after being evaluated for LASIK in another practice, where a photorefractive keratectomy was recommended. The patient, who was a mild myope with low cylinder, had no recent refractive changes and she denied eye rubbing.

The patient’s best-corrected vision was 20/20. The maps did not show any abnormality and the genetic testing was inconclusive. The patient became pregnant and any refractive considerations were postponed.

A third case was that of a man aged 27 years, who presented for a LASIK evaluation. The patient was a mild myope and previously wore contact lenses. The refraction was stable. His maps showed slight corneal thinning but a good residual stromal bed. His father had a history of keratoconus. Dr Garg said that for this patient, genetic testing is the next step and may help in the treatment plan.

“Genetic testing is new and holds a lot of promise,” Dr Garg concluded. “It helps us to risk-stratify our patients, help with clinical quandaries, and hopefully will facilitate earlier diagnosis and screening for keratoconus. It is important that the disease is not binary but rather a spectrum. Patients must understand that if they undergo genetic testing it will not determine whether they have keratoconus. Genetic testing will provide another data point to help identify keratoconus.”

This article is adapted from Dr Garg’s presentation at the American Society of Cataract and Refractive Surgery’s annual meeting in Washington, D.C. He is a consultant to Avellino and Glaukos.

1. Torres Netto EA, Al-Otaibi WM, Hafezi NL, et al. Prevalence of keratoconus in paediatric patients in Riyadh, Saudi Arabia. 

2. Chen S, Li XY, Jin JJ, et al. Genetic screening revealed latent keratoconus in asymptomatic individuals. 

According to one study, when genetic testing is coupled with advanced imaging, the chances of identifying keratoconus early are greater.

Genetic testing for keratoconus facilitates earlier recognition of condition

Vernal keratoconjunctivitis (VKC) is a progressive, vision-threatening condition. However, it is rare and may not be in the forefront of clinicians’ minds when evaluating a child with a persistent allergic ocular surface complaint. In fact, 88% of clinicians in one study noted that primary care physicians and paediatricians commonly under-diagnose or misdiagnose the disorder—which then goes untreated or undertreated—largely because the later involvement of the cornea can be misleading.

This finding was reported by Dr Leonard Bielory, a professor of medicine, allergy, immunology, and ophthalmology at Hackensack Meridian School of Medicine in Nutley, New Jersey, United States. The limited awareness of VKC is the focus for Dr Bielory, who emphasised it as a barrier to timely identification and management of this disruptive ocular surface disorder. Frequently, VKC is initially misidentified as an allergy or infection, and referral to a specialist is often delayed until symptoms have become severe.

VKC begins in the warmest months worldwide. This characteristic can lead clinicians to confuse it with springtime (or “vernal”) allergic conjunctivitis. The corneal inflammatory component, however, emerges later and is recurring. As Dr Bielory stated, “The condition is thought to mislead clinicians into thinking it is just a seasonal problem [but it] may also have a perennial component that develops with time.”

The key factor, Dr Bielory said, is that VKC should be considered in children who present with a persistent ocular allergic complaint, which may be the more pronounced type of conjunctivitis that can affect the cornea. A clue to diagnosis may emerge when parents report using over-the-counter (OTC) ocular treatments to no avail. “This should be the trigger to additional, more thoughtful involvement by their clinicians, such as referral to allergy specialists and ophthalmologists,” he advised.

The following timeline may be helpful, Dr Bielory explained. During the patient’s first season with an ocular reaction, vernal conjunctivitis and seasonal conjunctivitis may have similar presentations. During the second season of the allergic response, however, the vernal component (associated with warmth and different regional pollinating seasons) begins to progress more than the seasonal component, which remains seasonal.

Then, possibly during the second and third seasons, a great degree of progression may be seen during the year of sensitisation, bearing in mind that there are individual degrees of progression among patients. The patient then moves into the clinical phase.

Dr Bielory explained that a confounding factor in the diagnosis of VKC is how allergies develop (i.e., over time) in infants and young children. Immunoglobulin G antibodies inherited from the mothers protect babies for about 6 months. Immunoglobulin E, the allergy antibody, requires exposure to an offending agent over time, followed by development of the immune response against that agent.

Allergies may begin to manifest in babies 6–9 months after birth. Allergies exhibit nasal and ocular symptoms (rhinoconjunctivitis) in almost equal proportions, as physicians should know.

During the second year for children with developing VKC, symptoms worsen and become more unresponsive to treatment. An allergy work-up is needed, but, Dr Bielory stated, when ocular corticosteroids are prescribed and the patient does not improve, clinicians should suspect something more than seasonal allergic conjunctivitis (i.e., the vernal component).

Minor VKC symptoms include photophobia, tearing, burning and pruritus, with minimal impact on a patient’s quality of life. This scenario is often misdiagnosed as pink eye or allergic conjunctivitis.

Moderate VKC symptoms include photophobia, pruritus and discharge of mucus, with moderate sizes and numbers of cobblestone papillae in the upper tarsal conjunctiva or around the edge of the cornea (limbal form of VKC). Patient quality of life is moderately affected.

Severe symptoms of photophobia, pruritus and discharge of mucus, are accompanied by large cobblestone papillae, punctate epithelial erosions and Horner-Trantas dots. Quality of life is substantially affected, and the disease can potentially threaten vision if left untreated as it starts to affect the visual axis of the cornea.

As mentioned, OTC ocular treatments will not work. Use of oral antihistamines may cause increased ocular dryness over and above the abnormal tear film development in the vernal component.

“With antihistamines, there begins to be an increase in tear film dysfunction that comes with the allergy affecting the ocular surface,” Dr Bielory said. “However, in VKC, over-production of tears in response to corneal irritation usually leads to practitioners increasing the use of antihistamines, compounding the ocular surface issue,” he added.

Nevertheless, within this less-than-clear clinical picture, several treatments can be called into play. Treatment of the ocular surface progresses from lubricants to ophthalmic antihistamines to corticosteroids. Dr Bielory uses the steroid burst treatments over 1–2 weeks to avoid increases in intraocular pressure.

He advised that physicians should be aware of the chronic inflammation that induces the activity of certain cell types that will lead to corneal involvement. At this point, Dr Bielory explained, steroid-sparing treatments should be introduced, such as ciclosporin, which decreases the overall immune response of IL-2 and the cytokines.

Ciclosporin ophthalmic emulsion 0.1% (Verkazia,Santen), a steroid-sparing drug, is the first and only topical immunomodulator approved by the United States Food and Drug Administration for treating adults and children with VKC. In addition, Sinusol Breathe Easy (DRBRX), a non-steroidal OTC product, works by clearing nasal mucus and decongestion, which also benefits the ocular symptoms associated with allergies.

In addition to his role at Hackensack Meridian School of Medicine, Dr Bielory is an adjunct professor at the Center of Aerobiological Research at Rutgers University in New Brunswick, New Jersey, US; and director of the Center of Aerobiological Research at Kean University in Union, New Jersey. Dr Bielory is a consultant to Santen Pharmaceutical and DRBRX.

Ophthalmologists should look past the eyes in patients presenting with a persistent ocular allergic response and be mindful that sight-threatening vernal keratoconjunctivitis is a possibility.

Circumnavigating the bumpy road to vernal keratoconjunctivitis: Time is key

Patients who present for cataract surgery are increasingly younger and more active and are therefore interested in a greater degree of spectacle independence without the limitations of standard monofocal IOLs. The loss of intermediate vision may have a particular impact on these patient’s lives, as they spend more time in front of computers and smart ‘phones.

To provide a balance between distance and near vision, the use of monofocal IOLs to produce a monovision set-up has been well established. Although we often see a high level of patient satisfaction with this approach, monovision has its limitations, including tolerance issues due to anisometropia, loss of binocular stereoacuity and asthenopia.

By using Rayner’s RayOne EMV IOL (RAO200E; 

), my patients are achieving an extended depth of vision without the limitations of standard monofocal IOLs or the side effects associated with diffractive multifocal IOLs. The lens offers an extended depth of field via controlled positive spherical aberration, which can be used with and without monovision to increase the patient’s range of focus.

This lens has a non-diffractive optic and is therefore not expected to produce the side effects that are usually associated with diffractive IOLs such as night vision disturbance and loss of contrast. Although a high level of spherical aberration may induce night vision disturbances when certain thresholds are exceeded, there is a therapeutic range of spherical aberration in which night vision disturbances are not experienced because they are effectively filtered and processed by the brain.

In fact, while treating patients who had problems with night vision and loss of contrast in low light, which were common in patients with very small optical zones who had undergone laser surgery in the 1980s and 1990s, Prof. Dan Reinstein found that some degree of spherical aberration was therapeutic.

 At these levels of spherical aberration, depth of field was increased, but no night vision disturbances were experienced by the patient.

In my patients who receive this lens, my goal is to produce “modified monovision”. The additional controlled spherical aberration produces superior distance vision in the non-dominant eye and superior near vision in the dominant eye compared with what could be achieved with a standard monofocal IOL in a “standard monovision” setup (

I usually target plano in the dominant eye, and I choose a target refraction of −1.50 D in the non-dominant eye. This target for the non-dominant eye is consistent with an offset my colleagues and I have already used successfully in the settings of PRESBYOND and LASIK,

 which also combines spherical aberration induction and monovision.

The outcomes achieved with this strategy avoid patient intolerance and the other drawbacks seen with standard monovision. This approach provides a broad range of spectacle independence across the visual range, and the wide range of functional vision achieved allows for a better range of refractive error tolerance, without glare and halos or drop in contrast.

In patients who have already had corneal laser refractive surgery, I am sometimes hesitant to use this lens since they will likely already have a raised level of corneal spherical aberration. Raising it further may risk exceeding the therapeutic level. In these patients, I explain that their eyes already have increased depth of focus due to their previous laser treatment and that standard monofocals can be used to achieve “modified monovision”.

My patient interactions begin by establishing their daily visual needs and asking what they hope to achieve with their cataract surgery. In those with substantial cataracts, I explain that any option will result in improved quality of vision.

Beyond this initial expectation, the question then becomes the amount of spectacle independence that they hope to achieve with surgery. I review both monofocal and multifocal options and explain the potential limitations to multifocal IOLs such as the potential impact on night vision and loss of contrast.

I first discuss the option of standard monofocal vision with one eye set for near vision and one eye set for distance vision, without synergy between eyes, which is tolerated by about two-thirds of our patients. I explain that intermediate vision is not likely to be covered in this scenario.

I then discuss the concept of “modified monovision” as a strategy to overcome these limitations, with one eye set to predominantly manage distance vision and one eye to predominantly manage near vision but working in synergy to provide a better depth of field and some degree of intermediate vision that is independent of spectacles.

I feel that it is important to under-promise and over-deliver, and the fact that multiple strategies currently exist to improve vision in patients undergoing cataract surgery suggests that no solution is perfect for every patient. I explain to all patients that no presbyopic treatment can guarantee complete independence from glasses. For instance, most patients will continue to require spectacles for reading the small print of medicine bottles or watching live performances at far distances.

Overall, I have aimed for a target vision goal of −1.50 for the reading eye and have yet to find a patient needs follow-up laser surgery to address anisometropia. However, I do explain to my patients that a LASIK enhancement is a safe option to reduce the myopia if they do not tolerate it.

In contrast, if a patient does not tolerate a multifocal IOL then only lens exchange will remedy the situation. Overall, I have seen excellent levels of patient satisfaction in those who have received the RayOne EMV with this goal of modified monovision, and I have been very pleased with the results so far.

Suggestions for those new to modified monovision

Surgeons who are not comfortable attempting a modified monovision setup and who do not typically manage presbyopia may still see promising results with a standard plano target with this lens. This is because the depth of field offered will likely enable the patient to read text of a reasonable size in good light.

As the surgeon develops confidence, with patient experience, they may begin to target some myopia in the reading eye to increase the range of spectacle independence achieved.

Mr Alastair Stuart, BMBS, BMedSci, FRCOphth, PGDip CRS, Cert LRS

Mr Stuart completed his ophthalmology training in London and the South of England, UK, culminating in a corneal fellowship at Moorfields Eye Hospital followed by a fellowship in refractive surgery at the London Vision Clinic. He joined Optegra as a cataract and refractive surgeon in December 2021. He is a key opinion leader and consultant for both Rayner and Carl Zeiss Meditec, from which he receives payment for scientific reports and presentations.

Pseudophakic monovision: a clinical guide

2. Barrett GD. Consistently the best of both worlds: modest monovision as a strategy for balancing near and far vision.

3. Reinstein DZ, Archer TJ, Couch D, et al. A new night vision disturbances parameter and contrast sensitivity as indicators of success in wavefront-guided enhancement. 

4. Reinstein DZ, Couch DG, Archer TJ. LASIK for hyperopic astigmatism and presbyopia using micro-monovision with the Carl Zeiss Meditec MEL80 platform.

In “modified monovision”, which can be achieved with a new IOL, one eye predominantly manages distance vision and the other near vision—as with standard monovision—but the extended depth of field provides a degree of intermediate vision that is independent of spectacles.

A new lens option for enhanced monovision performance

The European Society for Cataract and Refractive Surgery (ESCRS) plans to welcome delegates to the Milano Convention Centre in Milan, Italy, for the fortieth time this year, and, judging by the preliminary online programme overview, there is a great variety of ophthalmology sessions on offer.

Taking place from 16–20 September 2022, and following the success of last year’s congress, the 40th ESCRS will again be a face-to-face event but supported by a virtual conferencing platform that will allow the sessions to also be streamed.

At the time of going to press, the ESCRS had not released the full, in-depth programme, however, a range of symposia, programmes, video sessions and workshops will be on offer and are discussed in this brief preview article. There will also be a daily exhibition, enabling delegates to learn about the latest technological advancements in ophthalmology and providing networking opportunities.

New for 2022 is the ESCRS iNovation Day. The agenda for iNovation Day includes discussions on the most urgent clinical needs and the use of technology to address them, along with perspectives from the European investment, regulatory and research communities. In parallel to this, the World Society of Paediatric Ophthalmology will be holding their Subspecialty Day.

Also new this year are the “Cornea Day” and “Glaucoma Day” streams that are due to take place throughout the day. Cornea Day topics will include cataract surgery in patients with ocular comorbidities; ocular surface and anterior segment surgery; and developments in posterior lamellar keratoplasty, keratoconus and cross-linking, whilst Glaucoma Day will cover profiling glaucoma patients, hints for cataract surgeons who are considering MIGS, surgical complications and surgical controversies.

The Main Symposium to be held at the end of the afternoon will be on the topic of “Emerging Treatment Options for Corneal Endothelial Disease”. There will also be an IME Symposium with the title “Phaco complex cases.”

Three instructional courses to be held at the end of the day will cover the topics of “Different Ways of Secondary IOL Implantation without Capsular Support”; “DALK: From Basic to Advanced”; and “Endophthalmitis after Cataract Surgery”. Finally, the Exhibition Hall will open at 13:00 on Friday and remain open until 18:00.

Saturday sees the Opening Ceremony of the Congress take place at 10:00, which should provide attendees with a feel of what to expect during the yearly event. This is due to be followed at 11:00 by the Main Symposium on “Demystifying IOLS optics”.

Elsewhere, the “Young Ophthalmologists Programme” is running “Starting Phaco” which includes video cases submitted by young ophthalmologists. This programme also offers junior ophthalmologists the chance to network and pick up useful information.

At 16:00 there will be an IME Symposium on Presbyopia IOLs and at 17:00 a Video Symposium on the topic of “Challenging Cases”.

A three-part Refractive Surgery Didactics Course will be ongoing on Saturday. The first session at 08:30 covers diagnostic techniques; the second session at 10:45 is entitled “Therapeutic Techniques: Intraocular Surgery”; and the final session at 14:00 covers “Therapeutic Techniques: Corneal Surgery”.

Throughout the day, Clinical Research Symposia will be held on: “Digital Medicine – 6 Steps for a Better Future”; “Ocular Tissue Engineering”; “Advancement of IOL Optic – How Far Can We Go?” and last-but-not-least, on the very hot topic in ophthalmology at the moment: gene therapy.

A total of 28 instructional courses will be running throughout the day on Saturday. The majority of these are 90 minutes long and start at 08:30, 10:30, 14:00 and 16:00. Shorter one-hour courses begin at 14:30. Free Paper Sessions and Presented Poster sessions will also be taking place and the Exhibition Hall will be open from 09:00 to 18:00.

The Main Symposium, on “High Volume Cataract Surgery”, will take place at 11.00 on the Sunday. The JCRS Symposium will be held at 14:00 and a Video Symposium at 16:15 entitled “Surgical Complications: You Make the Call” is sure to draw curious ophthalmologists.Early evening sees the IIIC Symposium at 18:15 on “The Perfect Save: Challenging Cases Managed by International Experts”.

Workshops on Visual Optics will be being held throughout the day, starting with “Visual Function – Visual Behaviour” at 08:30; “Ocular Biometrics/IOL Optics and Calculation” at 10:50 and finally “Imaging of the Human Eye” at 14:00.

Also at 14.00, a “Case Report” Session aims to delve into “Preoperatory Complications and Difficult Manoeuvres”. Meanwhile, there will be a Young Ophthalmologists Session at 16:30 on “Cataract and Corneal Issues”. A Practice Management Masterclass, on how ophthalmologists can optimise the patient experience, will also take place on the Sunday; the exact timings for this are yet to be confirmed.

A further 27 Instructional Courses will be held, starting at 08:30, 10:30, 14:00, 14:30 and 16:30. These cover a broad range of topics including “Corneal Regeneration Therapy and Surgery”, “Enhanced Monofocals and EDOF IOLs” and several aspects of cataract surgery.

Monday morning has two Main Symposia, beginning with the Heritage Lecture at 10:30 and followed at 11:00 by a session entitled “Where Are We in Intracorneal Implantation?” An IME Symposium on the subject of “3D Cataract Microscope Visualisation” will be held at 13:00.

A Video Session on “Getting Into Trouble” should provide delegates with some useful tips on overcoming surgical challenges at 14.00. Throughout the day there will be the opportunity to attend Practice Management workshops and the Free Paper Sessions and Presented Poster Sessions continue to run.

At 16:15 the CSCRS Symposium will be held on the subject of “The Patient Journey in Cataract Surgery.” There will also be an ISRS Symposium at 18:15 to end the day.

Instructional Courses also continue with 33 taking place, again starting at 08:30, 10:30, 14:00 and 16:00. Topics covered include “The Art and Science of Personalizing Refractive Outcomes in Cataract Surgery and Beyond”; “When Cataract Meets Glaucoma”; “All You Need To Know About Contact Lenses as a Refractive Surgeon”; and “Phaco Nightmares and Worst Case Scenarios”.

The final day of the Congress starts at 08:00 with an Orbis Symposium on “Innovative Ophthalmology in Conflict Zones” and a concurrent Presbyopia Workshop titled “Is there a change in the paradigm of presbyopia correction?” The final Main Symposium of the ESCRS at 10:30 is on the eye-catching subject of “How Not to Be Surprised by Refractive Surprise”.

The Free Paper Sessions continue, as do a series of Wet Labs starting at 08:00 and 10:30.There will be a final twelve Instructional Courses starting at 08:30 and 10:30, including courses on “Tips and Tricks for Challenging Cataract Surgery” and “Ocular Trauma Assessment and Management”.

The Congress finishes with the ever-popular “Best of the Best” session starting at 12:45 which highlights the best parts of the meeting.

Taking place from 16–20 September 2022, and following the success of last year’s congress, the 40th ESCRS will again be a face-to-face event but supported by a virtual conferencing platform that will allow the sessions to also be streamed. 

Congress of the ESCRS reaches milestone age

Optic neuritis (inflammation of the optic nerve) arises from numerous causes including infections (e.g. herpes zoster and Lyme disease), vaccines’ adverse events and autoimmune diseases.

 Optic neuritis is, for example, the presenting symptom in about 20% of multiple sclerosis (MS) cases.

 Acute optic neuritis also characterises neuromyelitis optica spectrum disorder (NMOSD), a rare but severe autoimmune disease.

In at least 70–80% of NMOSD cases, immunoglobulin G (IgG) autoantibodies to the water channel protein aquaporin-4 (AQP4) are detectable in the serum and play a relevant role in disease pathogenesis.

Many of the remaining cases arise from autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG). As the name suggests, oligodendrocytes as well as myelin sheaths express MOG.

 These cases should now be diagnosed as a separate disease entity, MOGAD (myelin oligodendrocyte glycoprotein antibody associated diseases).

Although NMOSD is rare, ophthalmologists 

optometrists need to remain aware of it as a potential differential diagnosis. Early diagnosis and rapid treatment maximise the chances that patients will fully recover their vision.

 As “time is retina,” this article aims to reduce the delay to diagnosis by reminding ophthalmologists 

 optometrists about NMOSD’s ocular hallmarks.

NMOSD is rare: the incidence is between 0.4 and 2 per 1,000,000 person-years and the prevalence 0.5 to 4 per 100,000.

 Ethnicity largely accounts for the variation.

 AQP4-NMOSD is more common in people of Afro-Caribbean descent than in other ethnic groups.

Several human leukocyte antigen (HLA) alleles and other polymorphisms seem to be associated with the risk of developing NMO. The particular HLA alleles depend on the population studied.

 So, as with other autoimmune diseases, genetic predisposition seems to be influential in determining NMOSD risk.

Age at presentation can help differentiate NMOSD from MS. The peak age of diagnosis for MS is between 25 and 35 years of age whereas, in European studies, the median age at onset for AQP4-NMOSD and MOGAD was 40 and 31 years, respectively.

 As a rule of thumb, the age of onset is about a decade later in NMOSD than in MS.

Moreover, MOGAD is the most common neuroinflammatory disease in children.

Most autoimmune diseases are more common in females than males. Indeed, females account for between 70% and 90% of relapsing AQP4-NMOSD cases.

 MOGAD, in contrast, shows little sex-related epidemiological difference.

 The incidence and prevalence of NMOSD will probably increase over the next few years, reflecting greater awareness, improved differential diagnosis, earlier diagnosis and better treatments.

NMOSD is characterised by attacks of acute optic neuritis and transverse myelitis (inflammation of the spinal cord).

 The spinal cord involvement offers another point of differentiation from MS. Long spinal cord lesions that extend over three or four vertebral segments, which are very rare in MS, often show on magnetic resonance imaging (MRI) of people with AQP4-NMOSD.

In some cases, the autoimmune attack involves the brain stem, and spinal cord lesions can extend into the medulla oblongata.

 The optic nerve often shows longitudinally extensive lesions on MRI, occasionally involving the chiasm.

 In contrast, MS tends to cause short lesions.

AQP4 is expressed predominately by astrocytes, which have numerous roles including regulating the development and permeability of the blood–brain barrier. Increased permeability of the blood–brain barrier may allow IgG to access the central nervous system (CNS).

Astrocytes also contribute to information processing, dispose of old and damaged organelles and modulate neurotransmitter levels in the CNS.

 AQP4 regulates changes in the extracellular volume that modulate the concentration of solutes and, in turn, neuronal electrical activity. As such, AQP4 modulates neuronal transmission and excitability.

In people with NMOSD, the autoimmune attack on AQP4 produces dysfunctional astrocytes and can cause astrocyte death. The autoimmune attack also triggers bystander inflammation, whichexposes other, usually hidden, autoantigens and can damage oligodendrocytes and neurons.

Symptoms of acute optic neuritis resulting from the disease can resolve in treated rapidly.

Ophthalmology Times Europe September 2022

Corneal ectasia part 3: OCT epithelial thickness measurements allow monitoring of corneal changes

Genetic testing for keratoconus facilitates earlier recognition of condition

Circumnavigating the bumpy road to vernal keratoconjunctivitis: Time is key

A new lens option for enhanced monovision performance

Congress of the ESCRS reaches milestone age

Time is retina: Focus on the ocular aspects of neuromyelitis optica