Approved for use in Europe, the small-aperture IOL IC-8 (Acufocus) is proving to be a very useful implant, particularly for patients who are not good candidates for current multifocal (MF), accommodating or extended depth-of-focus technology. 

The small aperture lens approach to vision correction is based on pinhole optics—a novel property not found in other available lenses.

The pinhole optic blocks out-of-focus, stray light, thereby creating a depth of focus with the small aperture of 1.36 mm allowing for a continuum of vision. 

The lens is forgiving, with a broad landing zone that makes it virtually immune to up to 1.50 D of astigmatism, while at the same time offering high-quality, sharp vision and less concern with photic phenomena.

The IC-8 is a single-piece, hydrophobic acrylic IOL embedded with an opaque mini-ring. Besides Europe, it is also approved for use in Asia and is currently being investigated in clinical trials in the United States.

A retrospective comparative review of studies assessed the range and quality of vision with small-aperture, accommodating or MF IOLs.

The IC-8 IOL was found to enhance vision at all distances, with improved visual acuities and a broad range of continuous functional vision. 

Likewise, the patients receiving this implant experienced superior intermediate vision and binocular mesopic contrast sensitivity, which is comparable to the other lenses.

The small-aperture IOL was paired with an aspheric monofocal IOL and compared with bilateral implantation of the MF lens Acrysof ReSTOR +3.00 D (Alcon) and MF IOL Tecnis +4.00 D (Johnson & Johnson Vision), and with the accommodative Crystalens AO (Bausch + Lomb). 

The IC-8 cohort comprised 105 patients,with the Restor, Tecnis and Crystalens platforms implanted into 25, 22 and 26 study subjects, respectively.

Investigators examined 6-month postoperative monocular uncorrected and distance-corrected vision at distance (4 m for IC-8, 6 m for others), intermediate (67 cm for IC-8, 80 cm for others) and near visual acuities (all 40 cm). 

They looked at defocus curves (binocular for IC-8, monocular for others) and compared binocular mesopic contrast sensitivity with and without glare.

The defocus curves revealed that the small-aperture lens had a 4.50 D continuous expanse of vision compared with 4.50 D for Restor, 4.00 D for Tecnis and 2.50 D for Crystalens – but the latter three were not continuous. 

Rather, the others showed a dip in the middle range for intermediate vision

The IC-8 IOL and Crystalens gave excellent intermediate vision, better than MFs, and MFs produced better near vision. The mean uncorrected near visual acuity (UNVA) for the new lens was 0.18 and 0.19 for the Tecnis. The Restor lens performed better with a UNVA at 0.01; Crystalens had a worse UNVA at 0.26 (

All four IOL groups had a similar mean uncorrected distance visual acuity (0.02–0.11). The small-aperture lens and Crystalens had a mean uncorrected intermediate visual acuity of 0.08 and 0.07. This was almost a 2-line improvement over Restor and Tecnis (0.24, 

Unwanted visual effects such as blurring, fluctuating vision and ghosting were of low severity in all the lenses studied, with a very low ghosting score for the IC-8 lens. 

Along with the Crystalens, the small-aperture IOL elicited very few reports of halos when both were compared with the two MF lenses, which received higher scores for halo and glare 

With regard to contrast sensitivity, the lenses were binocularly comparable. For contrast sensitivity with and without glare, the IC-8 lens and Restor groups were similar across all spatial frequencies. 

The small-aperture lens group was worse than Crystalens at 6 cycles per degree (cpd), but better than Tecnis at 3 cpd, and with no glare (

When compared with accommodating or MF IOLs, the IC-8 IOL enhanced vision at all distances and provided both improved visual acuities and a broad range of continuous functional vision. 

Likewise, the patients receiving this lens experienced superior intermediate vision and binocular mesopic contrast sensitivity comparable to the other lenses.

The IOL has minimal impact on the ability to visualise the retina with optical coherence tomography or on visual fields. 

One study recently showed that even with bilateral implantation, patients experience a minimal change in contrast.

The expanded depth of focus with the small-aperture lens allows refractive surgeons to target roughly -0.75 D without really losing much distance.

The IC-8 lens proved tolerant of up to 1.00 D deviation from the refractive target and it corrects up to 1.50 D of corneal astigmatism free from the concerns that accompany toric technology. One should remember that every degree of rotation is about a 3.3% reduction in the offset of the astigmatism.

In addition, toric lenses do not come in every power. Even just 0.75 D of residual astigmatism has a significant impact on MF lens performance at all distances.

In studies of the IC-8 IOL versus the standard monofocal implanted contralaterally, even those small-aperture eyes that miss target by 0.50 D to 1.50 D still experience only a slight impact on vision – maybe within 1 line on an EDTRS chart. With the monofocal on the other hand, the result can be as much as 3 lines if the target it missed.

The IC-8 IOL should prove particularly useful for patients with previous refractive surgery and corneal aberrations, extending to those with irregular astigmatism from trauma, a small iris defect or in a pupil that is not completely round, for example. 

In eyes with any type of irregularity or an aberrated cornea that could cause a high angle kappa and therefore impact the central ring, the implant should be a ‘shoo-in’.

For those patients who are not good candidates for other premium technology, the IC-8 lens gives surgeons something unique to offer. 

This IOL is forgiving in terms of hitting both targets, sphere and cylinder with a broad landing zone; has a very low dysphotopsia rate; and results in high patient satisfaction. In fact, 95% of small-aperture patients reported that they would undergo the procedure again.

Dr Pepose is a professor of clinical ophthalmology at Washington University’s School of Medicine, United States, and director of the Pepose Vision Institute in St. Louis, Missouri. Dr Pepose is an investigator for the IC-8 IOL clinical study.

1. Pepose J. Evaluating visual performance of small-aperture, accommodating, and multifocal IOLs. Presented at: AAO 2019; October 11-15; San Francisco, California, US.

2. Ang RE. Visual performance of a small-aperture intraocular lens: first comparison of results after contralateral and bilateral implantation. J Refract Surg. 2020;36:12-19. Doi: 10.3928/1081597X-20191114-01.

3. Novis C. Astigmatism and toric intraocular lenses. Curr Opin Ophthalmol. 2000;11:47–50.

Articles

The one-piece, small-aperture IOL IC-8 was found in a retrospective comparative review of studies to enhance vision at all distances, with improved visual acuities and a broad range of continuous functional vision.

Small-aperture IOL poised to fill unmet need

The year is 2025, and I have just had my annual health check … at my local optometrist’s. Vision and eye health are fine given my age and I am now on my way to my family doctor as my oculomic profile flagged some concerns that need to be checked.

 This is the second year I have opted into this free screening service as part of my annual eye check and it now feels normal.

 software provides a systemic health profile based on my fundus photographs and optical coherence tomography (OCT) scans. Within five minutes of sitting down for my scans I have been alerted to the fact that I am mildly anaemic with an estimated haemoglobin of 10.2g/L. On the plus side, my retina-estimated biochemical profile is fine and my total cholesterol assessed at less than 200g/dL.

The biggest surprise was that my estimated systolic blood pressure (BP) is up at 140mmHg. I quickly checked against my smart watch, which agrees. The diastolic reading is always less accurate from the fundal images so they still do not tend to report that, and there are easier ways of measuring your BP!

The rest of the report includes a raft of things that they have 

 found – no early signs of dementia or other neurodegenerative diseases; no atrial fibrillation; estimated normal cardiac and renal function; no signs of systemic inflammation; and no metabolic disturbances.

From where I am sitting in 2020, this all seems possible – and likely. We are increasingly recognising the power of the information encoded within our eyes, captured on both two-dimensional fundus images and three-dimensional OCT scans.

The range of systemic variables we can predict will only increase but let us reflect on where we are now. In one of my favourite papers of all time, Poplin and colleagues developed an algorithm that could predict age, smoking status, body mass index, diabetes status and systolic and diastolic blood pressure from colour fundus images.

External validation of this algorithm showed impressive accuracy for most of these variables, although systolic BP was strikingly more accurate than diastolic BP. A similar approach has recently shown good performance in predicting haemoglobin levels,

 and I would expect that we will see an increasing number of associations for other blood and tissue constituents being published over the next few years.

But for me, the most exciting thing about the paper by Poplin et al was none of these things. Yes, the performance was impressive, but it was reasonable to predict that a machine learning approach could detect the subtle pathophysiological changes that we would expect to be present with increasing age: higher BP and so on. To a large extent this is doing the same as humans, but better.

What really blew me away was that it could predict the biological sex of an individual from their fundus photograph with a very high accuracy (AUC of 0.97). This was totally unexpected.

It may not be as useful as some of the other metrics, but it tells us something more profound: that there are more aspects of our health and biological status that are encoded within our eyes than we ever dreamed of. We just need to look for them.

These kinds of discoveries from routine ophthalmic imaging are only possible because of three things. Firstly, advances in machine learning with specific techniques such as deep learning that can manage the high-dimensional data contained within images such as fundus images and OCT scans.

Secondly, the computational power that enables these to operate on the scale of datasets required. Thirdly, and most fundamentally, we need the datasets of sufficient quality and scale to train and test them on. And this is, in fact, our greatest limiting factor to innovation in this space: the availability of data.

A health data research hub focused on eye health called aims to address this challenge. Launched in September 2019, INSIGHT

 forms part of the Health Data Research UK (HDRUK)

 initiative, which aims to “unite the UK’s health data to enable discoveries that improve people’s lives.” It is a non-profit organisation supported by ten of the UK’s major health and science funders.

INSIGHT seeks to make health data available to researchers and innovators so that together we can better understand diseases and find ways to prevent, treat and cure them. The programme is designed to enable discovery and innovation in the field of oculomics, through enabling safe and appropriate access to deidentified data at scale. We think of it as a ‘biobank for ocular imaging’, with the ability to link to other relevant clinical data.

The datasets for INSIGHT initially came from the two founding NHS partners – Moorfields Eye Hospital NHS Foundation Trust and University Hospitals Birmingham NHS Foundation Trust. The nature of the populations across London and Birmingham makes this data exceptionally diverse in terms of ethnicity and socio-economic status, and with the NHS being available to everyone in the UK, using such data means some of the selection biases that may occur in other health systems are minimised.

Our existing resource is around ten million retinal images, but this is increasing by thousands of scans across multiple modalities every day across our existing network of hospitals. Building from our initial hospitals, we are looking forward to welcoming other NHS trusts and community eye health providers who have expressed their support for this initiative and their desire to scale INSIGHT across the UK.

Not only does this increase the scale of data—something which is particularly important for rarer conditions—but also ensures that all parts of the UK are represented when it comes to testing hypotheses or the performance of AI systems prior to implementation at a national level, for example in diabetic retinopathy screening or community monitoring of age-related macular degeneration.

We are working with NHS patients and the wider public to establish exactly how the system will operate with two areas of central importance: data access and the sustainability framework. Our charity partner Action Against AMD (AAAMD) has been leading on the development of a data trust advisory board, with strong patient and public representation that will form the framework for evaluation, assess incoming applications and will provide the ongoing scrutiny of data access through the programme.

Along with HDRUK nationally, we are also engaging with patients and the public to agree a sustainability model that is considered fair and returns value to the NHS. INSIGHT and other health data hubs are funded for 3 years by the UK government and various industry partners, but in order to continue, it will need to charge for its services in order to be sustainable and return value to the NHS.

In addition to the NHS Partners, and AAAMD, the health hub also includes both an academic partner (University of Birmingham) and two industry partners—Roche and Google Health—who are contributing their expertise and experience in a range of areas including pharmaceutical development, real world evaluation, technology data architecture and data security.

Principles of participation for all partners of INSIGHT and for HDRUK ensure that the datasets created are not exclusive to partners, and that there is no preferential access – all applications for data access will undergo the same rigorous and independent level of scrutiny against patient benefit and data safety. Additionally, all data accessed through the system will be deidentified, and applications will be evaluated against the ‘five safes’ of data security and international standards.

The aim, ultimately, is to improve people’s lives through facilitating and accelerating research that makes a difference in the real world. Building databases are costly in terms of time and resources, and they depend on the support and engagement of our patient communities.

However, we see this as an investment to enable others to do amazing things. We hope that the programme will help others to discover new insights into sight-threatening disease, to automate and improve the quality of screening and diagnosis, and even open up the possibility of ‘oculomic’ screening services for systemic health.

Wagner SK, Fu DJ, Faes L, et al. Insights into systemic disease through retinal image-based oculomics. Translational Vision Science & Technology. 2020;9. doi

Poplin R, Varadarajan AV, Blumer K, et al. Prediction of cardiovascular risk factors from retinal fundus photographs via deep learning. Nature Biomedical Engineering. 2018;2:158-164.

Mitani A, Huang A, Venugopalan S, et al. Detection of anaemia from retinal fundus images via deep learning. Nature Biomedical Engineering. 2020;4:18-27.

Prof. Denniston is a consultant ophthalmologist at University Hospitals Birmingham NHS Foundation Trust, UK, honorary consultant ophthalmologist at Moorfields Eye Hospital, honorary professor at the University of Birmingham and director of INSIGHT, the health data research hub for eye health. He has no financial disclosures.

A UK health data research hub containing vast numbers of fundus and OCT images opens the door to improved screening and diagnoses of eye diseases and even ‘oculomic’ services for systemic health.

Insights into the future of eye care

The respiratory symptoms caused by the severe acute respiratory coronavirus disease (COVID-19) that has been sweeping the world since late 2019 are well documented, given the regularity and consistency with which they occur. However, the role of the eyes and tears both as entry routes for the causative virus, SARS-CoV-2, and as sources of contagion are still the subject of debate, and relatively less is known about the ophthalmic implications of the disease.

It would appear from some recent studies that patients who experience the more severe forms of COVID-19 and present with pneumonia commonly display ocular symptoms. However, the authors of a recent Chinese study of 38 patients concluded that although a third of patients with the disease had ocular abnormalities, there was a low prevalence of the virus in tears1,2.

Nevertheless, it is possible that contact with infected eyes could be a route of transmission of SARS-CoV-2, especially given the knowledge that it can be spread via direct or indirect contact with other mucous membranes (the mouth and nose), so ophthalmologists should err on the side of caution and ensure rigorous prevention protocols are put in place.

In a literature review recently published in 

, Prof. Jorge Alió and Dr Alejandra Amesty reported that when it occurred, conjunctivitis was the most common ophthalmologic sign related to coronavirus infection1. And there are clues from previous coronavirus outbreaks as to why this should be the case: inflammation of the conjunctiva was first associated with a human coronavirus back in 2004 when children started to fall prey to the symptoms during the severe acute respiratory syndrome (SARS) crisis.

Genetically speaking, SARS-CoV-2, the virus that caused SARS, is around 70% similar to SARS-CoV and uses the same receptor (ACE2) to insert itself into human cells. This is potentially quite significant when one considers that ACE2 receptors have been found in the aqueous humour3.

But could the fact that conjunctivitis is mainly being seen in the most poorly patients mean that the presence of the virus on the surface of the eye and subsequent ocular events are down to decreased immune function? The researchers do not think so: “Both viral diseases and immune problems can lead to ocular manifestations, such as conjunctivitis, uveitis, retinitis, among others. It is difficult to determine the pathology of the ophthalmic involvement. However, since the virus has been cultured from conjunctival secretions, COVID-19 ophthalmopathy is more likely to be related to the actual virus infestation rather than the secondary immune reaction that the infection may cause.”

Any sign of conjunctivitis in the clinical setting should be considered to be a “possible coronavirus conjunctivitis, especially when accompanied by other respiratory tract problems or fever”, the authors pointed out.

Thankfully, viral conjunctivitis usually amounts to no more than an uncomfortable nuisance, so treatment strategies are typically supportive in nature. That said, it is important to try to lessen the potential viral load on the ocular surface and some of the general ophthalmic recommendations for viral conjunctivitis could also apply to COVID-19 patients.

“These include hygienic measures (frequent hand washing, especially when eye drops need to be applied or contact lenses worn; avoiding touching or rubbing the eyes; changing pillowcases, sheets) … we should be meticulous when examining patients who have tested positive for COVID-19.”

The close face-to-face proximity of ophthalmologists to their patients and frequent exposure to tears and ocular discharge, as well as regular handling of equipment such as slit lamps, tanometers and lasers, means they are perhaps at a higher risk of contracting COVID-19 than other types of healthcare professionals, the researchers said, referring to recent guidelines that have been published in an attempt to minimise the chances of infection spreading in ophthalmology clinics and hospital departments.4,5

In the guidance, ophthalmologists are advised to impose limits on the number of attending patients and to adhere to strict appointment timetables to prevent people from gathering in clinic waiting rooms. Online platforms, such as hospitals’ official websites, should be readily used, whilst simply making more telephone calls could reduce the need for patients to visit hospitals, for example, by helping them to distinguish between urgent and nonurgent ocular problems.

The guidelines go on to recommend triage systems to help to flag up patients with symptoms consistent with COVID-19 infection such as fever, and online ordering and delivery of prescribed medication, especially for chronic eye diseases such as glaucoma.

Recommendations for handling a patient’s visit include:

Reducing the number of accessible entry points to the hospital/clinic;

Screening patients for COVID-19 symptoms and contact history with confirmed or suspected within the past 14 days;

Seeing patients with eye infections in separate clinics with their own waiting areas;

Testing patients more than twice for evidence of SARS-CoV-2 RNA in the conjunctival sac and tears;

Limiting numbers of people in examination rooms;

Ensuring rooms are well ventilated and instruments used disinfected immediately after a patient’s visit; and

In addition, slit lamps should be protected by shields and direct ophthalmoscope examination could be replaced by slit light lenses, optical coherence tomography or fundus photography.

For inpatients, the suggested adaptations include preoperative infection screening and use of local rather than general anaesthesia to avoid contamination. Negative-pressure operating rooms should be used for emergency operations on any COVID-19-positive patients.

Human coronavirus is believed to be able to remain infectious on inanimate surfaces for as many as 9 days6, so disinfecting surfaces with water, detergent and commonly used disinfectants is extremely important, Prof. Alió and Dr Amesty explained. In addition, they suggested that some ocular spray disinfectants that contain hypochlorous acid (usually applied to treat blepharitis in order to reduce bacterial and viral load on the skin and eyelashes) could be used as “a measurement of prevention for the facial area where many other chemical agents cannot be applied”.

However, more studies are needed to establish a specific antiviral product that could be used to reduce the viral load on infected patients’ conjunctiva and lower the transmission rate via the eyes/tears. The authors conceded that this is no easy task when “so many doubts still remain regarding the ophthalmic implications” of the infection.

Summarising, the authors have called for “well-designed trials” to be conducted “to rule out other ocular manifestations [besides conjunctivitis] that may result from COVID-19 infection and to better elucidate the mechanisms of transmission through the eyes.”

Until more light can be shed on the ophthalmic implications of COVID-19, ophthalmologists can only remain as up-to-date as possible on emerging disease findings, whilst maintaining a cautious approach when dealing with patients before, during and after appointments.

1. Amesty MA, Alió del Barrio JL, Alió JL. COVID-19 disease and ophthalmology: An update.

https://doi.org/10.1007/s40123-020-00260-y

Wu P, Duan F, Luo C, et al. Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei Province. China 

https://doi.org/10.1001/jamaophthalmol.2020.1291

Holappa M, Vapaatalo H, Vaajanen A. Many faces of renin-angiotensin system—focus on eye. 

Lai THT, Tang EWH, Chau SKY, et al. Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong. 

Yong Y, Ruixue T, Xu S, et al. A comprehensive Chinese experience against SARS-CoV-2 in ophthalmology. 

Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents

Prof. Alió is professor and chairman of ophthalmology at the Miguel Hernandez University of Elche and scientific director at Vissum in Alicante, Spain. He has no financial interests in the subject matter.

Emerging data on conjunctivitis cases in COVID-19 patients necessitate high levels of caution and a meticulous approach during the pandemic.

The ophthalmic implications of COVID-19: What we know so far 

A study found that the ICE2 procedure was more effective than iStent/phacoemulsification with no added risk. Safety was excellent in both groups.

Minimally invasive glaucoma surgery (MIGS) has changed the way we approach the management of glaucoma. MIGS offers the glaucoma surgeon safe and effective surgical options that have lowered the threshold for surgery, which was traditionally reserved for advanced or rapidly progressive disease.

The mindset of the glaucoma surgeon now has to evolve as well. Surgeons and patients should work together to take control of this blinding disease and no longer be a passenger.

This approach, often termed ‘interventional glaucoma’, requires the surgeon and patient to take an active rather than passive role in the management of glaucoma. Ocular surface disease, side effects of topical treatment and non-adherence should be addressed at every clinic visit to see whether more effective treatments can be offered.


	We are now entering the era of combination MIGS and exploring how to maximise the cumulative effects of these surgeries whilst maintaining the excellent safety profile that is its foundation.
	
	Synergistic approaches to lowering intraocular pressure (IOP) are not novel; they have been used in topical treatment for many years, such as combining beta blockers to target inflow and prostaglandins to improve outflow.

The iStent (Glaukos Corporation) reduces IOP when used alone or during cataract surgery. This ab interno stent bypasses the trabecular meshwork, improving the eye’s ability to drain aqueous into the Schlemm’s canal. The device is safe and effective for patients with mild-to-moderate open-angle glaucoma.

When implanted during cataract surgery, the implant adds to the potential IOP-lowering effect of phacoemulsification, which may reduce IOP to a small degree in open-angle disease and to a greater extent in primary angle-closure glaucoma.

 
	
	I have always been pleased with the reduction in IOP after iStent and phacoemulsification. I wondered whether adding endoscopic cyclophotocoagulation (ECP; BVI Medical) would enable me to achieve an even lower IOP postoperation. This could result in more of my patients’ glaucoma being controlled, as well as reducing the risk of them requiring filtering surgery in the future.

ECP safely and predictably decreases aqueous production through targeted ablation of the ciliary processes, thus lowering IOP.

 It is appropriate for the vast majority of patients, but it is contraindicated for underlying macular pathology such as macular oedema or a history of uveitis.

We recently completed a study that has been published in the 

 comparing the outcomes for patients undergoing phacoemulsification with two iStents versus phacoemulsification with two iStents and ECP (ICE2 procedure).

 The longitudinal retrospective study took place over 12 months, with 63 eyes receiving the ICE2 procedure and 46 eyes receiving treatment without ECP.

We evaluated IOP, best-corrected visual acuity (BCVA) and number of medications at baseline, with follow-up at 1 and 5 weeks, and 3, 6 and 12 months. The primary outcome was IOP reduction at 12 months. The results were as follows:
	
	• For the primary outcome of IOP reduction at 12 months, patients in the ICE2 group fared better. IOP decreased by 35% from medicated baseline, compared with 21% for iStent/phacoemulsification. Although the ICE2 group had higher IOPs at baseline, their final IOPs were lower (approximately 13 mmHg versus 14 mmHg).
	• Both surgeries had a very similar safety profile. At week 1, the ICE2 eyes and the iStent/phacoemulsification eyes all looked very quiet. We found no added risk to the combined procedure, and there was no delay in patients’ postoperative visual recovery in the ICE2 group.
	• Both groups had a similar reduction in medication at 12 months and similar final BCVA.
	• ECP added about 5 minutes to surgery.


	In essence, the ICE2 procedure was more effective than iStent/phacoemulsification, with no added risk. Safety was excellent in both groups.

After seeing the promising safety and efficacy of ICE2 at 1 year follow-up, I will continue to use this surgery for the appropriate patients moving forward. When we can get pressures down to 13, we know that a large proportion of patients’ glaucoma will not progress.

More studies are needed, ideally in the form of randomised trials. We need to establish whether the effect of ICE2 is sustained at 3 and 5 years.

We have already started studies that will assess the patients’ ocular surface and quality of life after MIGS, including ICE2. IOP control and disease control is the most important aspect of treatment, but the eye comfort and quality of life of our patients should not be overlooked.

1. Wellik SR, Dale EA. A review of the iStent trabecular micro-bypass stent: safety and efficacy. Clin Ophthalmol 2015;9:677-684.
	2. Guedes RAP, Gravina DM, Lake JC, et al. Intermediate results of iStent or iStent inject implantation combined with cataract surgery in a real-world setting: a longitudinal retrospective study. Ophthalmol Ther 2019;8:87-100. 
	3. Craven ER, Katz LJ, Wells JM, et al. Cataract surgery with trabecular micro-bypass stent implantation in patients with mild-to-moderate open-angle glaucoma and cataract: two-year follow-up. J Cataract Refract Surg 2012;38:1339-1345.
	4. Thomas R, Walland, M, Thomas A, Mengersen K. Lowering of Intraocular Pressure After Phacoemulsification in Primary Open-Angle and Angle-Closure Glaucoma: A Bayesian Analysis. Asia Pac J Ophthalmol (Phila). 2016 Jan-Feb;5(1):79-84.
	5. Armstrong JJ, Wasiuta T, Kiatos E, et al. The effects of phacoemulsification on intraocular pressure and topical medication use in patients with glaucoma: a systematic review and meta-analysis of 3-year data. J Glaucoma 2017;26:511–522.
	6. Friedman DS, Jampel HD, Lubomski LH, et al. Surgical strategies for coexisting glaucoma and cataract: an evidence-based update. Ophthalmology 2002;109:1902–1913.
	7. Vizzeri G, Weinreb RN. Cataract surgery and glaucoma. Curr Opin Ophthalmol 2010;21:20-24.
	8. Yip LW, Yong SO, Earnest A, et al. Endoscopic cyclophotocoagulation for the treatment of glaucoma: an Asian experience. Clin Exp Ophthalmol 2009;37:692-697.
	9. Lima FEL, Carvalho DM, Avila MP. Phacoemulsification and endoscopic cyclophotocoagulation as primary surgical procedure in coexisting cataract and glaucoma. Arq Bras Oftalmol 2010;73:419-422.
	10. Kahook MY, Lathrop KL, Noecker RJ. One-site versus two-site endoscopic cyclophotocoagulation. J Glaucoma 2007;16:527530.
	11. Francis BA, Berke SJ, Dustin L, et al. Endoscopic cyclophotocoagulation combined with phacoemulsification versus phacoemulsification alone in medically controlled glaucoma. J Cataract Refract Surg 2014;40:13131321.
	12. Lindfield D, Ritchie RW, Griffiths MF. ’Phaco-ECP’: combined endoscopic cyclophotocoagulation and cataract surgery to augment medical control of glaucoma. BMJ Open. 2012 May 30;2(3).
	13. Pantalon AD, Barata ADO, Georgopoulos M, Ratnarajan G. Outcomes of phacoemulsification combined with two iStent inject trabecular microbypass stents with or without endocyclophotocoagulation. Br J Ophthalmol. 2020 Jan 24.


	GOK RATNARAJAN, BSC, MBBS, FRCOPHTH, MD
	E: g.ratnarajan@gmail.com
	Dr Ratnarajan is a consultant ophthalmic surgeon and director of glaucoma at the Eye Unit in Queen Victoria Hospital, East Grinstead, UK. He has received honorariums from BVI.

Endoscopic cyclophotocoagulation adds cumulative advantage to MIGS

Studies show that the micropulse laser represents a safe treatment for macular disorders involving the foveal area. Further and larger studies are needed to prove the real effectiveness related to all the macular pathologies, but it can be used as an add-on to treat complex cases.

The micropulse laser represents a relatively new frontier among retinal specialists. The subthreshold energy it can deliver without damaging retinal tissue is being exploited in various macular diseases, including central serous chorioretinopathy (CSC), diabetic macular oedema (DME), and macular oedema due to branch retinal vein occlusions (BRVO).

There is increasing evidence that subthreshold micropulse laser (SML) treatment (Iridex) can serve as an additional valuable therapeutic option to intravitreal injections (anti-VEGF and/or steroids), mostly for retinal vascular diseases. And, since standardised therapies or established ‘best practice’ guidelines do not yet exist for CSC, the opportunity exists for the micropulse laser to join the armamentarium, particularly in those patients which do not tolerate eplerenone tablets. In my clinical practice, I am currently using the laser sub-threshold therapy to treat CSC both as monotherapy and in combination with systemic treatments, such as eplerenone or spironolactone.

Conventional laser photocoagulation is widely used to obtain thermal and beneficial effects on the retina; however, it can induce side effects such as chorioretinal atrophy, formation of epiretinal scars, choroidal neovascularisation and visual field defects

. The SML acts only to stimulate retinal pigment epithelium (RPE) cells to regulate different factors, such as anti-VEGF inhibitors, pigment epithelium-derived factor (PEDF) and permeability factors, sparing the neural retinal and preserving the functional integrity of the photoreceptors

 delineated well the difference between conventional laser photocoagulation and the micropulse mode. A conventional laser is characterised by the so-called continuous wave (CW) mode, in which the laser energy is delivered with a single pulse, whereas the micropulse mode delivers a train of repetitive short pulses (typically of 100–300 ms), with alternating ‘on’ and ‘off’ times.

The length of time the power is ‘on’ divided by the total time the laser is used gives rise to a ratio known as the ‘duty cycle’. The presence of the so-called ‘off’ time allows the heat to dissipate, thus minimising the thermal effect and reducing retinal injury.

As rigorously covered in recent review by Scholz et al.

, there are currently two different types of micropulse laser. The first is a diode laser with a wavelength of 810 nm, which is able to penetrate up to the choroid.

The other available SML system is the 577-nm yellow laser, which has the advantage that the xanthophyll, a pigment present in the macular layers, absorbs only a minimal amount of yellow light, thereby increasing the safety of a laser procedure close to the fovea. The development of navigated laser systems has considerably improved the accuracy and safety of the micropulse laser treatment. The eye-tracking technology minimises the eye movements of patients, and the presence of special software allows one to plan treatment based on the images obtained with fluorescein angiography (FA) and/or indocyanine angiography (ICG), optical coherence tomography (OCT) and OCT angiography.

In my hospital-based setting, I use the micropulse laser mode with a navigated system and, based on the different macular diseases, I optimise the treatment with the multimodal imaging modality. For example, in the case of CSC, I acquire the FA and ICG images where possible to evidence a typical leakage hot spot, as well as the OCT scan, to demonstrate the presence of subretinal fluid (SRF).

After taking a fundus photo of the patient’s macula, the navigated system is able to superimpose the fundus photo and the OCT/FA/ICG images, and, finally, I can perform the micropulse laser with different energies and duty-cycle at the level of the hot spot evidenced by the FA/ICG and directed to the SRF as illustrated by the OCT scan.

Before the era of anti-VEGF and intravitreal injections, laser photocoagulation was the standard treatment for DME, but severe complications such as accidental foveal damage and expansion of macular scars were observed, and so the method took a back seat. However, the recent advent of SML has provided a new age for the laser treatment of DME and researchers have sought to assess the safety and efficacy of this therapeutic approach.

 evaluated functional and morphological parameters after SML treatment with both infrared and yellow systems, showing that the lowest duty cycle (5%) setting seemed to be the safest in order to preserve the visual function and maintain the macular integrity. Moreover, Chhablani et al.

 demonstrated the safety of the two most-used subthreshold parameters (duty cycle 5% and 15%) of the yellow laser compared with conventional laser and found that the 15% duty cycle achieved better anatomical, visual and functional outcomes.

In my routine laser practice, with DME patients, I usually set the duty cycle to 10% with a power energy between 120 and 160 mW, associated with the laser-navigated treatment mode. So far, I have not had any cases of choroidal neovascularisation, photoreceptor integrity damage or laser-related visual function deterioration, which I believe demonstrates how safe the micropulse procedure is.


	Another interesting field is the application of the micropulse laser for the treatment of patients with macular oedema (MO) following an episode of BRVO. As recently summarised in a review by Eng et al.

, SML appears to be safer than conventional laser photocoagulation and is as efficacious, improving visual function and reducing the intraretinal fluid accumulation in such patients.

In a small retrospective series presented by our team at the European Society of Retina Specialists (EURETINA) congress, we analysed the safety and efficacy of the yellow navigated micropulse laser treatment in 17 patients (18 eyes) affected by MO due to BRVO with a follow-up of 3 months. We observed a statistically significant improvement of the visual acuity without a corresponding decrease in macular thickness.

Interestingly, we found that the photoreceptor structures were restored, particularly in terms of renewal of the ellipsoid zone integrity. Moreover, confirming the previous data regarding the safety of the procedure, we saw no cases of chorioretinal atrophy, scarring or choroidal neovascularisation. We had set the duty cycle to 10% and used 130 mW as medium energy with circa 600 spots at the level of the increased macular thickness (see Figure 1A–C).

Combining the micropulse laser with intravitreal injections can help to reduce the burden of numerous injections. In a recent study, Terashima et al.

 determined the efficacy and safety of the combination therapy between the yellow SML and intravitreal ranibizumab, showing that visual acuity was maintained with a decreased number of intravitreal procedures needed.

I agree with this treatment modality and in my practice I tend to combine the intravitreal approach (anti-VEGF and steroid implants) with the micropulse laser to tackle the disease in different ways, and so reduce patients’ stress and achieve the best functional result.

The standardised treatment for CSC has been the subject of debate due to the lack of data from randomised controlled trials. The first pilot study to investigate the role of micropulse laser treatment for CSC was presented in 2003

. The SML (with 810-nm diode laser) led to the complete resorption of SRF 1 month after the treatment with no recurrence at 6-month follow-up.

Since 2003, many different studies have analysed the efficacy of the micropulse laser for chronic CSC, with encouraging results. Nevertheless, the PLACE trial

, an open-label, multicentre, randomised, controlled clinical study, recently demonstrated that a significantly higher proportion of patients receiving half-dose photodynamic therapy (PDT) achieved complete resolution of SRF and functional improvement than those subjected to high-density SML (HSML).

However, in the literature there are other interesting studies which prove the efficacy of the micropulse laser for cases of CSC. For example, Kim et al.

 conducted a retrospective study with a 3-year follow-up demonstrating a complete SRF reabsorption in 81.5% of patients affected by chronic CSC who were treated with yellow 577-nm SML. 

Unlike the other published studies, which used a conventional treatment duration of 100–300 ms, the research group opted for just 20 ms, with a 15% duty cycle and a power ranging from 200 to 400 mW, applying the energy both over the area of RPE leakage and all areas of serous retinal detachment, including the fovea.

In my clinic, I follow the indications of the previous study, but slightly modifying the parameters: for the leakage point assessed by multimodal imaging modality (FA/ICG), when it is located far away from the foveal zone, I use a 15% duty cycle, 20-ms treatment duration and 300 mW of energy; whereas, for the SRF, mostly if it is localised at the foveal level, I usually use a 10% duty cycle, 20-ms duration and 150-mW energy, in order to stimulate only the RPE cells, avoiding damage to the foveal area.


	Studies show that the micropulse laser represents a safe treatment for macular disorders involving the foveal area. Regarding the efficacy, the results are not still uniform and for this reason we need further and larger studies to prove the real effectiveness related to all the macular pathologies.

In my opinion, we can currently consider the micropulse laser as an additional therapy, which may help physicians to treat disorders with complex pathophysiology, such as DME, MO due to BRVO, and CSC. The feasibility of using the micropulse laser in combination with intravitreal injections in the case of MO related to vascular disorders offers the potential to relieve the burden of injections, help with patient compliance and optimise functional outcomes.

In the case of CSC, the laser acts as another therapeutic option besides PDT with minimal risks and good efficacy, both as monotherapy and when associated with other treatment strategies, such as eplerenone and spirinolactone.

1. Seiberth V, Alexandridis E, Feng W. Function of the diabetic retina after panretinal argon laser coagulation. Graefes Arch Clin Exp Ophthalmol. 1987;225(6):385-390.
	2. Ulbig MR, Arden GB, Hamilton AP. Color contrast sensitivity and pattern electroretinographic findings after diode and argon laser photocoagulation in diabetic retinopathy. Am J Ophthalmol. 1994;117(5):583-588.
	3. Dorin G. Evolution of retinal laser therapy: minimum intensity photocoagulation (MIP). Can the laser heal the retina without harming it? Semin Ophthalmol. 2004;19:62-68.
	4. Scholz P, Altay L, Fauser S. A Review of Subthreshold Micropulse Laser for Treatment of Macular Disorders. Adv. 2017;34:1528-1555. 
	5. Vujosevic S, Martini F, Longhin E, Convento E, Cavarzeran F. Subthresold micropulse yellow laser versus subthresold micropulse infrared laser in center-involving diabetic macular: Morphologic and Functional Safety. Retina. 2015;35:1594-1603.
	6. Chhablani J , Alshareef R , Kim DT, Narayanan R,  Goud A et al. Comparison of different settings for yellow subthreshold laser treatment in diabetic macular edema. BMC Ophthalmol. 2018;18:168.
	7. Eng VA, Leng T. subthreshold laser therapy for macular oedema from branch retinal vein occlusion: focused review. Br J Ophthalmol. 2020 Feb 7 [Online ahead of print].
	8. Terashima H, Hasebe H, Okamoto F, Matsuoka N, Sato Y et al. Combination therapy of intravitreal ranibizumab and subthreshold micropulse photocoagulation for macular edema secondary to branch retinal vein occulsion: 6 month result. Retina. 2019;39:1377-1384. 
	9. Bandello F, Lanzetta P, Furlan F, Polito A. Non-visible subthreshold micropulse diode laser treatment of idiopathic central serous chorioretinopathy. A pilot study. Investig Ophtalmol Vis Sci. 2003;44:4858.
	10. van Dijk EHC, Fauser S, Breukink MB, Blanco-Garavito R, Groenewoud JMM et al. Half-dose photodynamic therapy versus high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy: the PLACE trial. Ophthalmology. 2018;125:1547-1555.
	11. Kim YJ, Kim SY, Ha S, Moon D, Seong S et al. Short-duration multiple-session subthreshold micropulse yellow laser (577 nm) for chronic central serous chorioretinopathy: results at 3 years. Eye (Lond). 2019;33:819-825.


	EMILIANO DI CARLO, MD
	E: emi.dicarlo@hotmail.it
	Dr Di Carlo is a vitreoretinal consultant at the ophthalmology department of the StÃ¤dtisches Klinikum Karlsruhe, Germany. His main interests are micropulse laser and new frontiers of vitreoretinal surgery. He has no financial interests in the subject matter.

CAMILLA SIMINI, MD
	E: camilla.9128@gmail.com
	Dr Simini is an ophthalmology resident at StÃ¤dtisches Klinikum Karlsruhe, Germany, which is directed by Prof. A.J. Augustin. Her main interests are: medical and surgical retina. She has no financial disclosures.

A new frontier in micropulse laser treatment for retinal disorders

When paired with multifocal extended depth-of-field technology, the new, small aperture ocular IOL, IC-8, delivers excellent extended depth of focus at near, far and intermediate ranges whilst reducing halo and glare.

A new small-aperture ocular IOL, IC-8 (Acufocus), which is CE Marked and currently under investigation by the United States Food and Drug Administration (FDA) employs the pinhole camera effect to correct presbyopia. By flattening the defocus curve on both the myopic and hyperopic sides, the IOL essentially creates a small amount of myopia, thereby extending the patient’s depth of focus and eliminating visual effects from corneal astigmatism or other irregularities.

This high-technology, one-piece hydrophobic acrylic ocular implant comprises an embedded opaque annular mask with a central aperture. Aligned light rays converge through the 1.36-mm central aperture, while peripheral defocused and, often, aberrated rays are blocked from disrupting the image.

As a result, patients experience a continuous range of vison from near to far, including the increasingly important intermediate range. At 1.5- to 7-feet away, the intermediate range represents a critical zone of activity for most people. It is where we eat most of our meals, do our desk work and watch the majority of our large-screen media. It is where many people earn their livings, including refractive surgeons.

Originally intended to be paired with a monofocal IOL, it has been found that, when paired with a multifocal IOL, the IC-8 is better than previous alternatives at enhancing visual acuity at intermediate distances, and so has the potential to benefit this underserved cohort. Likewise, patients who have had previous refractive procedures are becoming more common.

As they proliferate, so does our necessity for techniques and technologies tailored to support their special needs. The IC-8 has shown good outcomes in these ‘veteran’ surgical patients.

Surgeons are only now beginning to appreciate the additional benefits made possible by combining the small-aperture lens with IOLs that function on completely different optical principles. Experimentation is ongoing, and this novel strategy may ultimately lead us to maximise the full potential of the IOL, providing patients with truly satisfying customised outcomes.

LOW-ADD MIOLS 
	Low-add multifocal lenses (MIOLs) have been shown to improve intermediate visual acuity and offer surgeons the ability to further individualise patients’ visual outcomes, particularly when mixed with another refractive technology. Combining a multifocal lens with a different type of lens also can act to minimise glare and halo, an intrinsic characteristic of MIOL optics.

It is well known that most types of presbyopia-correcting IOLs-including multifocal refractive and diffractive, and even the newest trifocal technology-sacrifice distance vision to some extent in order to correct near vision and induce a variable amount of dysphotopsias.

 One study of the AcrySof ReSTOR +2.50 D IOL (Alcon) found it provided good intermediate and functional near vision for patients who did not want to accept the higher potential for visual disturbances associated with the +3.00 D version of the same IOL, but wanted more near vision than a monofocal IOL generally provides.

Another prospective comparative investigation evaluated bilateral cataract surgery using the +3.00 D AcrySof IOL or a +4.00 D power of the implant.

 The +3.00 D IOL provided superior uncorrected distance visual acuity, significantly better uncorrected intermediate visual acuity at 40, 50, 60 and 70 cm, and functional reading acuity at 38.9 cm. Eyes with the +3.00 D IOL had better intermediate vision than those with the +4.00 D model without compromising distance and near visual acuity.

MF EXTENDED DEPTH OF FOCUS
	The Lentis Mplus LS-313 MF20 (Teleon; available in Europe but not in the US) is a foldable, one-piece, aspherical multifocal posterior chamber IOL that extends a patient’s depth of focus. Its refractive rotationally asymmetric design helps minimise the loss of light to below approximately 7%, thereby improving contrast and retinal image quality.

An evaluation of the implant, with +2.00 D of near add compared with +3.00 D, found superior visual outcomes from far distance to a near of about 25 cm with the latter lens. The +2.00 D demonstrated excellent visual results from far distance to an intermediate distance of about 50 cm.

Unlike the aforementioned multifocal implants, the IC-8 IOL functions due to the pinhole effect: by reducing scattered light and permitting only parallel rays to reach the macula, depth of focus is extended and visual disturbances such as glare and halo are reduced. Small-aperture technology can even overcome problems with corneal asphericity and irregularities. Astigmatism up to 1.50 D can be corrected with the lens alone.

Typically, the IC-8 IOL is implanted in the non-dominant eye, with a monofocal lens in the contralateral eye. To enhance acuity, the small-aperture IOL can be paired with other technologies, such a multifocal, a low-add multifocal or even a trifocal lens. There are many combinations to consider, with the basic idea being that using different types of implants can enhance the sharpness of vision at near, intermediate and distance, and minimise the side effects of the competing technologies.


	The ongoing prospective, multicentre Mosiac study was undertaken to evaluate visual outcomes from the combination of the IC-8 IOL and the Lentis LS-313 MF-20.

 Our group presented 5-month follow-up data on 13 patients with bilateral implantation of the IC-8 IOL with the Lentis LS-313 MF-20 with +2.00 D of near add. We looked at parameters including:

Uncorrected and corrected (binocular) far, intermediate and near visual acuity;

Photic phenomena (halo and glare simulator).

Included were the 26 eyes of 13 patients with cataracts whose average age was 68.5±10.8 years. The targeted refraction for the IC-8 IOL eyes was –0.43±0.18 D with an achieved refraction of 0.42±0.41 D.

The achieved refraction was within ±0.50 D 62% of the time. The targeted refraction for the MF-20 eyes was –0.15±0.16 D and the achieved refraction was –0.33±0.42 D. The achieved refraction was within ±0.50 D 85% of the time.

We found that patients had excellent binocular visual acuity at far and intermediate distances, as well as functional vision at near. Furthermore, they had functional reading acuity at near and intermediate distances, and there was a comparatively low incidence of photic phenomena (see Figures 1 and 2). The combination of the small-aperture implant with a low-add multifocal lens like the Lentis LS-313 MF-20 is a good treatment option for patients who are motivated to achieve spectacle independence.

Multifocal lens designs can exhibit pronounced peaks and troughs, but the IC-8 IOL provides uninterrupted functional vision over 3.00 D of defocus.

 The small-aperture principle has the ability to produce a high-quality full range of vision without blurry zones, and it is more forgiving of refractive error misses or surprises.

The implant has been shown to provide good visual outcomes in post-LASIK and post-RK eyes

, making it an attractive option for patients who previously could not find an appropriate presbyopia-correcting IOL. Likewise, patients with corneal irregularities can benefit from the technology’s ability to reduce aberrations.

When paired with multifocal extended depth-of-focus (EDOF) technology, the IC-8 delivers excellent EDOF at near, far and intermediate ranges whilst reducing halo and glare. It can enhance the physician’s ability to customise successful visual outcomes for each patient, even for those who have undergone previous refractive surgeries. Based on the simple, proven and ancient understanding of the pinhole’s effect on light ray alignment, this IOL is a versatile tool to help cataract patients achieve their paramount postoperative visual goals.

1. Gundersen KG, Potvin R. Comparative visual performance with monofocal and multifocal intraocular lenses. Clin Ophthalmol. 2013;7:1979-1985.
	2. de Vries NE, Webers CA, MontÃ©s-MicÃ³ R, Ferrer-Blasco T, Nuijts RM. Visual outcomes after cataract surgery with implantation of a +3.00 D or +4.00 D aspheric diffractive multifocal intraocular lens: Comparative study. J Cataract Refract Surg. 2010;36(8):1316-1322.
	3. Linz K, Attia MS, Khoramnia R, et al. Clinical evaluation of reading performance using the Salzburg Reading Desk with a refractive rotational asymmetric multifocal intraocular lens. J Refract Surg. 2016;32(8):526-532.
	4. Venter JA, Pelouskova M, Bull CE, et al. Visual outcomes and patient satisfaction with a rotational asymmetric refractive intraocular lens for emmetropic presbyopia. J Cataract Refract Surg. 2015;41(3):585-593.
	5. Calvo-Sanz JA, SÃ¡nchez-Tena MA. Characterization of optical performance with defocusing curve: Analysis of two refractive intraocular lens models with high and medium addition. J Optom. 2018 Oct 31.
	6. https://www.healio.com/ophthalmology/cataract-surgery/news/online/%7B2809ee76-e466-43fe-b70b-dd94ff661925%7D/video-edof-iol-using-pinhole-effect-lessens-ocular-effects.
	7. Dick HB, Elling M, Schultz T. Binocular and monocular implantation of small-aperture intraocular lenses in cataract surgery. J Refract Surg. 2018;34(9):629-631.
	8. Dick HB. Small-aperture strategies for the correction of presbyopia. Curr Opin Ophthalmol. 2019;30(4):236-242.

GERD U. AUFFARTH, MD, FEBO
	E: auffarthg@aol.com
	Prof. Auffarth is chairman and medical director of the Department of Ophthalmology of the University Clinic of Heidelberg, Heidelberg, Germany, director of the David J. Apple, MD International Laboratory of Ocular Pathology, and director of the International Vision Correction Research Center in Heidelberg. He receives research grants and lecture fees from Alcon, Johnson and Johnson, Zeiss, Hoya, Oculentis, Rayner, Acufocus, KOWA and Biotech.

How pinhole camera effect in small-aperture implant corrects presbyopia

It is important to proactively consider night-time dryness as its own separate entity. An effective lid hygiene regime will minimise the risk of build-up of deposits on compromised lid margins and thus optimise long term success and tolerance in these patients.

The awareness of the high incidence, impact on daily life and challenges of treating dry eye disease (DED) has increased exponentially over the past 2-3 decades. Significant progress towards achieving consistency in understanding the fundamental causes of the condition, the systematic strategies used for diagnosis and stepwise treatment approaches have undoubtedly come from the two landmark Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop – DEWS I and II – reports.

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