The Yamane technique, first described by Shin Yamane and colleagues,

 is of use for intrascleral IOL fixation when a patient is aphakic without capsular support. It sparked my interest since I was seeking a solution for cases where iris fixation was not an option.

The technique offers an elegant and effective way to fixate the IOL in complex cases. I have had the opportunity to perform it several times and my first few cases provided me with some key takeaways as well as offering a unique perspective to identify areas for further improvement.

Thorough preparation, including practising in two wet labs before the first case, is a must, and the learning curve with the Yamane technique can be steep. However, it is also short. And whilst mastering a method usually requires a large number of cases, I have achieved great outcomes quickly by going back and reviewing videos and analysing my early experiences.

I was referred a patient with a posterior capsule tear during cataract surgery whose IOL had slipped nasally half inside and half outside the bag. The patient could no longer see well because the optic edge was now in the centre of the visual axis.

IOL exchange was scheduled. The dislocated IOL was carefully removed from the capsular bag and then cut into three pieces using 19g Packer/Chang IOL cutters (MicroSurgical Technology [MST]) for atraumatic removal from the anterior chamber. Following IOL removal, I inserted a CT Lucia lens (Zeiss) and both haptics into the anterior chamber.

I then sutured the main incision (which was larger than usual because of the IOL removal) with the intention of avoiding excess fluid leakage and maintaining the good pressure required for needle placement. I used a 23g Ahmed micro-grasper (MST) through the paracentesis for entry to grasp the haptics.

Placing the second haptic inside the anterior chamber made grasping and threading the haptic into the lumen of the needle much more challenging because the haptic slid into the angle. With hindsight, I should have left the trailing haptic outside of the eye; I will do so in the future.

In the next case, the patient’s lens had fallen into the posterior chamber during cataract surgery and the capsule was completely lost. During the pars plana vitrectomy and lensectomy, they endured a sector iridectomy. The patient presented to me with aphakia, no capsule, some loss of iris tissue and cystoid macular oedema.

I again elected to proceed with scleral fixation utilising the Yamane technique. This time, I used an AC maintainer included in the scleral IOL fixation solutions pack (SFP-1001, MST) to keep the eye firm.

The needle placements went well, and there was no fluid egress even with the trailing haptic exposed through the primary incision. The procedure went smoothly and as planned. The trailing haptic can also secure the IOL from falling back into the vitreous cavity, especially in this case because there was no capsular support and iris tissue was missing.

I proceeded with the iris repair, which required suturing of the sphincter. I used 23g Ahmed micro-tying forceps (MST) to hold each edge of the tear as I passed the needle (10-0 prolene suture on CTC-6 needle) through to complete the repair.

At the end of the case, I saw that the IOL was not perfectly centred even though I had been careful with the scleral measurements, so I pulled the haptic to one side to centre the optic. I then trimmed the excess haptic material and mushroomed and reburied the tip. The IOL was perfectly centred and there was no tilt at all.

Sometimes it can be difficult to mark accurately because the limbus is not always clearly defined. One can miss by half a millimetre due to difficulty in identifying a clear entry point. In this case, even though one marks at 2.5 mm, this may not actually be 2.5 mm from the limbus.

I believe this is what happened during the second case described above when I realised that the IOL was not well centred. One needle entered further from the limbus than the other, which affected the IOL positioning. Of note, each needle pass is performed by a different hand and at a different angle —it is difficult to be perfectly symmetrical but awareness of the issue certainly helps.

To know exactly where the positioning and entry points are (2.5 mm posterior to the limbus and 2 mm across), I like to open the conjunctiva and measure directly on the sclera to see as much as I can. Surgeons who have experience with this technique can go through the conjunctiva, but I feel it is less stressful when you have better visibility to watch the needle pass under the sclera before making the turn.

The sclera can also be held to prevent the eye from rotating, which helps with the needle tunnelling. If going directly through conjunctiva, the scleral tunnel is not visible. Finally, when turning the needle to enter the eye, go deep and not shallow: turn and go straight down and then come back up to visualise the bevel of the needle.

Keep in mind that the needles will be passed by both hands and that each hand will act differently: one comes forward while the other goes back. There are going to be differences between your hand positions, which is not a big problem, but one need to be mindful of this and make adjustments to get the same result from both hands. This is something that can be practiced with simulation model eyes.

Fixation of the globe is very important; otherwise the eye rotates, so the hand positions should be thought out ahead of time.

One might think that the haptic should thread directly into the needle, but in my experience, it is the opposite: threading the haptic is much easier if the needle is aimed toward the haptic while holding the haptic still. I use the 30g thin-wall needles with specialist holders from the scleral IOL fixation solutions pack (MST), which allow for manoeuvrability and control during this delicate step. To manipulate the haptic, my preferred micro-instrument is the 23g Ahmed micro-grasper (MST), which is a versatile micro-instrument for the anterior chamber.

My final recommendation would be to choose your cases wisely and have retina support available. Always prepare your equipment in advance.

I opt for the CT Lucia IOL (Zeiss) with PVDF haptics, which I find has the right proportion of flexibility and resistance to breaking. I also use the scleral IOL fixation solutions pack (MST), which includes the essential elements to perform the technique, including three 30g thin-wall needles with silicone hubs, two specialist needle holders, an AC maintainer, a marker and a calliper.

The Yamane technique can be easy to learn if one is prepared and well equipped. Even if things do not go perfectly the first couple of times, practice will help you learn from your mistakes and it will get easier!

Dr Amin is chief of complex anterior segment surgery at Westchester Medical Center, New York, United States. She has no financial disclosures relevant to this article.

1. Yamane S, Sato S, Maruyama-Inoue M, Kadonosono K. Flanged intrascleral intraocular lens fixation with double-needle technique. 

Articles

Practice makes perfect when adopting this method for intrascleral IOL fixation.

Mastering the Yamane technique: Key learnings from first cases

Polarisation-sensitive optical coherence tomography (PS-OCT) is a functional extension of the conventional form of OCT and exploits the polarisation properties of light. According to Dr Ritika Mullick, a fellow in Cornea and Refractive Services at Narayana Nethralaya Hospital, Bangalore, India, this imaging modality can aid the early recognition of disease-related changes before they can be seen topographically.

Dr Mullick explained that the human eye is known to have polarisation-altering tissues; using an ultra-high-resolution PS-OCT helps us to study the form birefringence caused by the underlying fibril structures in the corneal stroma. This, in turn, can enable users to detect subnormal distribution of collagen in corneal disorders.

In a clinic setting, this technology can demonstrate both normal corneal biomechanics and clear-cut cases of abnormalities, such as the development of post-SMILE ectasia.

The technology is especially useful in what Dr Mullick describes as “confusing” cases, which comprise about 35% of those that pass through her clinic. For example, upon examination, one patient had a thin cornea but no keratoconus; another had a suspicious presentation, but the biomechanics were normal; and yet another had normal topography but suspicious biomechanics. 

This raises the question: should physicians rely on the corneal topography or the biomechanics in such cases? This question spurred the development of PS-OCT, which can image the spatial distribution of fibril structures and their orientation.

As Dr Mullick explained, “The arrangement of collagen fibres in normal corneas exhibits a checkered pattern centrally. In the images, the presence of dark blue/purple indicates the least phase retardation: that is, the least alteration of polarised light, due to the uniform arrangement of the collagen fibres. This indicates a very healthy cornea.”

When corneas are diseased, however, irregular organisation of the collagen fibres can be seen, with more alteration of the polarised light; this indicates higher phase retardation, as seen by the warmer colours in the image.

Dr Mullick and her colleagues studied 135 corneas prospectively: i.e., 50 that were healthy, 50 with keratoconus and 35 suspicious corneas. All patients underwent corneal tomography, corneal biomechanics and epithelial mapping in addition to biomicroscopy, fundus evaluation and refraction.

The evaluations were followed by PS-OCT. The results were categorised based on the topographic and biomechanical analyses followed by 

 analysis of the phase retardation (PR) distribution. The Belin-Ambrosio enhanced ectasia display (BAD) software, which helps in the early detection of subclinical keratoconuschanges, was used with the inbuilt Oculus HR Pentacam camera system.

Dr Mullick provided some examples of representative cases. She reported that the 

 imaging by PS-OCT showed normal topography in two cases, but another case yielded a suspicious BAD deviation value (BAD-D).However, the checkered arrangement in the centre of the image indicated that the two corneas were healthy and therefore would be suitable candidates for refractive surgery.

A third case had normal BAD-D and suspicious biomechanics; this patient had a partial loss of the checkered arrangement. In this case, refractive surgery was deferred. The fourth case had a thin cornea and no keratoconus, but there was partial loss of the checkered arrangement.

In the fifth and sixth cases, with keratoconus and post-SMILE ectasia, respectively, there was a complete loss of the checkered arrangement, which indicated that these were weak ectatic corneas with weak collagenous arrangements.

This approach has facilitated the ability to diagnose disease earlier before it becomes apparent on topography. “PS-OCT can clearly identify differences in collagen fibre distributions between healthy and keratoconic corneas. Suspicious corneas had a unique distribution of collagen, which indicated early changes before they were detected on topography,” Dr Mullick commented.

She added: “The imaging technology can help diagnose keratoconus even in cases that have normal or borderline suspicious topography findings, and therefore can be an excellent screening modality.”

The technology can also be used to screen candidates for refractive surgery; identify forme fruste keratoconus; monitor keratoconus progression or follow cross-linking outcomes; perform post-graft imaging; or diagnose retinal disorders.

This article was adapted from Dr Mullick’s Subspecialty Day presentation at the 2021 American Academy of Ophthalmology annual meeting, New Orleans, Louisiana, United States. Dr Mullick has no financial interest in this subject matter.

Polarisation-sensitive optical coherence tomography has facilitated early diagnosis of disease before it becomes apparent on topography. 

The missing link in the recognition of corneal abnormalities 

According to the clinicaltrials.gov database, there are around 2,000 gene therapies currently under investigation worldwide in many areas of medicine. In recent decades, the discipline has rapidly evolved.

Whilst the focus of most gene therapies has so far been on rare diseases, many additional drugs/products are currently being studied to treat disorders such as cancer as well as genetic and infectious diseases. And around 20 gene therapies are already available in the United States, having received Food and Drug Administration (FDA) approval.

The are several available approaches in gene therapy. We can replace a disease-causing gene with a healthy gene or deactivate a gene that is not functioning properly. In addition, a modified or completely new custom-designed gene can be introduced to treat a disease.

The basic principle is to target missing or faulty genes in monogenic diseases. Usually the “gene therapy drug” is given only once; it carries an instruction to change the sequence of one or more proteins. This change is necessary if those essential proteins are produced in a faulty manner: either they are not produced in sufficient quantities or the catalysis process controlled by the protein is not working correctly.

Major pathobiochemical or pathophysiological pathways have been investigated intensively. Gene therapy products include plasmid DNA and viral or bacterial vectors: in a subset of diseases, cells are extracted, genetically modified and then re-introduced into the body but more commonly a viral vector is used, which entails eliminating the virus gene and using its ability to penetrate the cell to safely deliver the new information.

From an immunological perspective, the eye is the ideal target for gene therapy, which thus makes it likely that, in the future, highly successful gene therapy approaches will lead to cures for certain diseases of the eye.

In 2017, voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics) became the first FDA-approved ocular gene therapy. Also approved in Europe (since 2018), it is used to treat certain inherited retinal diseases such as 

-related Leber congenital amaurosis or retinitis pigmentosa.

As mentioned already, gene therapies focus on monogenetic diseases. The approach becomes much more complicated for diseases with many pathways involved, such as age-related macular degeneration (AMD). Hence, current methods focus on gene augmentation and/or suppression to enhance or reduce the production of a molecule that plays a crucial role in the pathogenesis of the disease.

In wet AMD, this is vascular endothelial growth factor (VEGF). Its antibody (anti-VEGF) needs to be applied on a monthly basis, which may lead to both clinical and adherence problems. One way to overcome this is a surgical intervention such as the implantation of a slow-release device. An alternative would be the augmentation of anti-VEGF-production using a genetic approach.

One candidate that is currently being studied is RGX-314 (Regenxbio). This drug is delivered subretinally or suprachoroidally. It contains a novel adeno-associated viral vector (AAV8) and is currently in development for wet AMD, diabetic retinopathy and other retinal diseases.

As described above, the cells are transfected, which delivers the information to produce a protein. This protein is designed to neutralise VEGF and, by doing so, modify the pathway for the formation of new leaky blood vessels and retinal fluid accumulation.

Both approaches, subretinal and suprachoroidal, are surgically challenging. However, the suprachoroidal method, which our group used for the application of other drugs more than a decade ago, has been redesigned and appears to be a safe way to apply such a drug.

The positive interim results of two trials of RGX-314 (AAVIATE and ALTITUDE) using in-office suprachoroidal delivery were presented by Dr Robert L. Avery at the most recent meeting of the American Academy of Ophthalmology. The studies are including wet AMD and diabetic retinopathy patients without centre-involved diabetic macular oedema.

Another drug candidate in development is ADVM-022 (Adverum Biotechnologies), an adeno-associated virus vector encoding aflibercept. Results to date have shown that a single intravitreal administration of ADVM-022 is able to provide a safe and effective long-term treatment option for both wet AMD and diabetic macular oedema.

Looking at dry AMD, the approach is similar. Rather than focusing on genes that are responsible for the disease, we are trying to produce or antagonise factors that are part of the pathogenetic cascade. Inflammation has been shown to play a crucial role in the pathogenesis of dry AMD.

One way to tackle inflammation is by increasing the production of complement factor I (CFI), also known as C3b/C4b inactivator (a protein that regulates complement activation). Doing so has been shown to reduce complement activity and thereby inflammation.

About 3% of patients suffering from dry AMD have CFI mutations, with lower CFI levels giving a higher risk of dry AMD. GT005 (Gyroscope Therapeutics) is a AAV2 vector that delivers a plasmid construct expressing normal CFI; it is currently under investigation with promising results and no significant side effects so far, although the drug does need to be applied subretinally.

As described, clinical studies of promising ocular gene therapies are underway. However, safety remains a concern in this area of therapeutic medicine, where retinal pigment epithelium (RPE) changes and inflammatory reactions can take place. Thankfully, there have been some reports that these potential side-effects can be successfully controlled by topical steroids.

Until now only patients who have been heavily pre-treated have been included in trials. As well as the need to conduct intensive safety assessments, before these new gene therapy approaches can be used on regular basis in real-world settings, Phase 3 trials need to be completed and surgical procedures taught.

And so, while we are entering a new era of drug therapy, with gene therapy having the potential to change the way many diseases are treated (good news for our patients), there is still much work ahead. Both drug safety and drug delivery issues present major challenges that need to be addressed.

One promising future approach lies in the CRISPR-Cas9 gene-editing tool, which has recently been introduced for the treatment of a hereditary human disease. It functions rather like a molecular scissor to snip parts of the DNA: in this way, we can insert, delete or modify genes.

After identifying the defective genes, this exciting technology will provide the next step in gene therapy. We are already underway and have identified the defective genes in other hereditary diseases. Thus, this new technology will first be used in diseases with a clearly defined genetic signature.

Dr Augustin is professor of ophthalmology and chairman of the Department of Ophthalmology at the Karlsruhe Municipal Hospital, Germany. He has no financial disclosures related to this article.

Promising gene therapies in development are pinpointing steps in the pathogenic cascades involved in ocular diseases, such as VEGF for wet AMD and CFI for dry AMD.

Making strides in ophthalmology with modern gene therapy techniques 

A recent Phase 1/2a trial of an intravitreal treatment designed to treat diabetic macular ischaemia (DMI), BI-X (Boehringer Ingelheim), found the candidate to be well tolerated with no dose-limiting events and no drug-related adverse events, according to Dr Quan Dong Nguyen, a professor of ophthalmology at Byers Eye Institute at Stanford University School of Medicine in Palo Alto, California, United States.

DMI is defined as any disruption in retinal vascularity within the superficial and/or deep retinal plexus as seen on optical coherence tomography angiography, and it is a complication of diabetic retinopathy (DR). Currently, there is no treatment available that can prevent or stop progression of DMI. Dr Nguyen pointed out that the development of a treatment is important because it is a common complication that can have a profound impact on a patient’s vision.

BI-X works as an anti-ischaemia modulator of the human protein, semaphorin 3A, which blocks revascularisation in ischaemic retinas.

DMI patients enrolled in the Phase 1/2a study had previously been treated with laser for DR. The study has two parts, or ‘phases’, and all subjects treated with BI-X have received one intravitreal dose of the drug.

The non-randomised, open-label section of the study is complete. Three cohorts received 0.5-, 1- or 2.5-mg doses of the therapy; the cohorts included three, three and six subjects, respectively. The primary endpoint was the number of dose-limiting events, and the secondary endpoints were the numbers of drug-related and ocular adverse events.

According to Dr Nguyen, the best-corrected visual acuity (BCVA) improved slightly compared with baseline in the subjects assigned to 1 and 2.5 mg of BI-X. No dose-limiting, drug-related or serious adverse events occurred. Three subjects experienced ocular adverse events: specifically, subconjunctival haemorrhage and ocular hyperaemia, both in the 0.5-mg cohort.

One vitreous detachment occurred in the 2.5-mg cohort. Four procedural-related adverse events occurred: subconjunctival haemorrhage, ocular hyperaemia and temporary intraocular pressure increase in the 0.5-mg group, and mild pain after the procedure in the 2.5-mg group.

The findings in the three cohorts were similar. The main take-aways from the SRD study were that BI-X was well tolerated by subjects with DMI in all three dosing cohorts and that the BCVA showed signs of improvement compared with baseline in the 1- and 2.5-mg cohorts.

In the second, ongoing, single masked and randomised segment of the study, the BI-X cohort (20 subjects) will receive three 2- to 5-mg doses separated by 4-week intervals and 10 subjects are to receive sham injections.

The primary endpoint is the number of drug-related adverse events; the secondary endpoints are the number of ocular adverse events and the changes from baseline in the foveal avascular area size, BCVA and central retinal thickness.

“Discovering a treatment for DMI is a major challenge for many clinician-scientists, as DMI can lead to significant visual loss, even if the diabetic macular oedema is well controlled,” Dr Nguyen concluded. “It is our hope that BI-X can be among the first successful treatments for this devastating complication of diabetic retinopathy.”

This article is adapted from Dr Nguyen’s presentation at the American Academy of Ophthalmology Annual Meeting. Dr Nguyen has received research funding from Boehringer Ingelheim.

An ischaemia modulator has demonstrated it is safe and well tolerated in a Phase 1/2a trial in diabetic macular ischaemia patients.

Promising early data with intravitreal diabetic macular ischaemia candidate

Over the past decade, minimally-invasive glaucoma surgery (MIGS) has revolutionised glaucoma management, offering a myriad of advantages such as minimal disruption of the eye’s natural anatomy and physiology, a shorter recovery period and an enhanced safety profile.

However, most MIGS approaches still alter the anterior chamber angle anatomy; for example, trabecular meshwork ablation using an electropulse or micro-trabecular bypass stents,which alter aqueous currents by creating an artificial pathway via one or two points of exit for aqueous humour.

In our practice we use canaloplasty to improve the flow of aqueous throughout the entire 360 degrees of the conventional outflow pathway without redirecting aqueous currents to a single point of exit. It offers a comprehensive approach by addressing all aspects of potential outflow resistance in the trabecular meshwork, Schlemm’s canal and collector channel systems, with proven safety and long-term efficacy in peer-reviewed studies.

Introduced in 2016, ab-interno canaloplasty is a physician-led refinement of traditional canaloplasty, entailing the intubation of Schlemm’s canal with a flexible microcatheter via a self-sealing, clear corneolimbal incision. This approach preserves the conjunctiva and thus can be used earlier in the treatment paradigm in cases of mild-to-moderate glaucoma. As an added benefit, it does not require a permanent implant in the eye.

We use the iTrack canaloplasty microcatheter (Nova Eye) and, more recently, the iTrack Advance. With an illuminated fibre optic tip, both devices provide continuous location feedback in addition to an internal guidewire mechanism that permits catheterisation of up to 360 degrees of the canal during a single intubation.

The ab-interno technique is based on the same principles as traditional canaloplasty and is defined as the 360-degree catheterisation of Schlemm’s canal to break obstructions and adhesions, followed by the subsequent viscodilation of Schlemm’s canal upon withdrawal of the microcatheter whilst injecting a high-molecular-weight hyaluronic-acid-based ophthalmic viscosurgical device (OVD).

This pressurised delivery of OVD dilates the canal, thus restoring the physiological aqueous outflow pathway. The tissue-sparing aspect of ab-interno canaloplasty allows future surgical options that rely on the preservation of the trabecular meshwork in patients who may need further intervention as the disease progresses.

This comprehensive approach makes ab-interno canaloplasty an effective treatment modality in a variety of glaucoma patients, including those with mild-to-moderate open-angle glaucoma (OAG) and those who are intolerant, non-compliant or unresponsive to anti-glaucoma medication.

Ab-interno canaloplasty can be performed either as a standalone procedure or combined with cataract surgery. Various studies have documented long-term efficacy for reduction of both IOP and anti-glaucoma medication burden along with a satisfying safety profile and low risk of severe complications up to 36 months following surgery.

The ab-interno technique is typically performed in cases of mild-to-moderate glaucoma and, to my knowledge, existing published literature does not incontrovertibly report clinical evidence with more advanced glaucoma stages. Furthermore, despite its minimal learning curve, familiarity with the gonioprism is a known challenge of all the MIGS procedures. In addition, the addition of the ab-interno canaloplasty procedure can add up to 10–15 minutes to traditional phacoemulsification.

I was one of the first surgeons to use ab-interno canaloplasty in Europe and I recently presented the results of our retrospective, monocentric, consecutive case series using the ab-interno surgical technique at the 2021 European Society of Cataract & Refractive Surgeons meeting in Amsterdam and published the 4-year results.

The study was conducted on 27 eyes of 22 patients with mild-to-moderate OAG experiencing insufficient IOP reduction or intolerance and non-compliance with glaucoma medication, also including a previously failed trabeculectomy. These patients underwent ab-interno canaloplasty with post-surgical follow-ups at 12, 24, 36 and 48 months.

The results were promising and demonstrated the efficacy of the procedure in reducing IOP and medication dependency, as well as patient complications. Mean IOP significantly reduced by 30% from baseline (

< 0.001), and the reduction was sustained 4 years postoperatively, from 19.8 ± 5.2 mmHg at baseline to 14.6 ± 3.0 mmHg at the last follow-up.

A significant reduction in mean medication usage was evident 4 years postoperatively as well, from 1.92 ± 1.00 at baseline to 0.89 ± 0.83, and we were able to significantly reduce glaucoma medication dependence by the fourth year. Indeed, 4 years postoperatively, 39% of the eyes required no medication, compared with none at baseline, and 72.2% were using one medication or less (

No serious complications were documented throughout the duration of the study, except for a case of limited descemetolysis near the limbus, which resolved spontaneously within 2 months. We surmise this was due to slow withdrawal of the catheter resulting in local over-delivery of OVD in the canal and subsequent temporary detachment of the Descemet membrane. Overall, our results suggest that ab-interno canaloplasty is not only effective but also a safe surgical procedure.

In 2022 we plan to start a prospective, non-randomised, multicentre study across four investigational sites in Europe, to assess the efficacy, safety and quality of life outcomes of canaloplasty combined with phacoemulsification and performed via an ab-interno approach using the new-generation iTrackAdvance, which has reengineered the previous microcatheter via a handheld injector design. This multicentre study, called CATALYST, will be performed over a 12-month period and will enrol up to 50 patients with mild-to-moderate uncontrolled OAG.

To sum up, in my experience, ab-interno canaloplasty offers significant versatility in real-world clinical practice and presents a useful tool in the glaucoma toolkit of comprehensive ophthalmologists and cataract surgeons, who typically see earlier-stage patients than their glaucoma surgeon peers. However, these encouraging results do not currently suggest that the technique can replace traditional glaucoma surgery or ab-externo canaloplasty, which we still use in our practice for more advanced glaucoma cases.

Ab-interno canaloplasty is effective in cases of controlled glaucoma, for patients who are intolerant or non-compliant to anti-glaucoma medications and thus have the treatment goal of reducing the number of medications required while maintaining IOP within target range, and possibly delaying the requirement for more invasive surgery and its subsequent increased risks and post-surgical complications.

Prof. Körber currently works at Augencentrum Koeln and at the Clinica Oculistica, University-Hospital of Padova, Italy. His areas of interest and expertise are cataract and glaucoma, with a special interest in canaloplasty. He has no financial or proprietary interest in any material or method mentioned but is the principal investigator for the Catalyst clinical study, which uses the product mentioned.

1. Lavia C, Dallorto L, Maule M, Ceccarelli M, Fea AM. Minimally-invasive glaucoma surgeries (MIGS) for open angle glaucoma: A systematic review and meta-analysis. 

2. Saheb H, Ahmed IIK. Micro-invasive glaucoma surgery: current perspectives and future directions. 

3. Nichamin LD. Glaukos iStent trabecular micro-bypass

4. Brandão LM, Grieshaber MC. Update on minimally invasive glaucoma surgery (MIGS) and new implants. 

5. Brüggemann A, Despouy JT, Wegent A, Müller M. Intraindividual comparison of canaloplasty versus trabeculectomy with mitomycin C in a single-surgeon series. 

6. Klink T, Sauer J, Körber NJ, et al. Quality of life following glaucoma surgery: canaloplasty versus trabeculectomy.

7. Khaimi MA. Long-term medication reduction in controlled glaucoma with iTrack ab-interno canaloplasty as a standalone procedure and combined with cataract surgery.

 27 Sep 2021. DOI:10.1177/25158414211045751.

8. Gallardo MJ, Supnet RA, Ahmed IIK. Circumferential viscodilation of Schlemm’s canal for open-angle glaucoma: ab-interno vs ab-externo canaloplasty with tensioning suture. 

9. Gallardo MJ, Supnet RA, Ahmed IIK. Viscodilation of Schlemm’s canal for the reduction of IOP via an ab-interno approach. 

10. Kazerounian S, Zimbelmann M, Lörtscher M, et al. Canaloplasty ab interno (AbiC) – 2-year-results of a novel minimally invasive glaucoma surgery (MIGS) technique. 

11. Koerber NJ, Ondrejka S. 4-Year efficacy and safety of iTrack ab-interno canaloplasty as a standalone procedure and combined with cataract surgery in open-angle glaucoma. 

12.Gallardo MJ. 24-month efficacy of viscodilation of Schlemm’s canal and the distal outflow system with iTrack ab-interno canaloplasty for the treatment of primary open-angle glaucoma. 

With minimally invasive surgery procedures becoming increasingly popular in glaucoma management, canaloplasty using an ab-interno surgical technique offers enhanced natural aqueous outflow in open-angle glaucoma.

A new treatment paradigm with ab-interno canaloplasty for POAG

I started my ophthalmology training in 1965 at Ghent University, Ghent, Belgium, in the department of Prof. Jules François, who was a man of many talents (author or co-author of 1,870 peer-reviewed articles; doctor honoris causa at 21 universities) and a very didactic teacher!

Later, I founded the Ghent University clinic department of ultrasound, where I stayed some 15 years as a consultant. In 1968 I started my private practice in Antwerp, Belgium, as a solo practitioner.

I have had the privilege to be a spectator, often a participant and sometimes a leader in the most important developments in ophthalmology over the 50-plus years since I started my ophthalmology career. It is my honour to share the most important learnings and developments with the reader.

Most of these happened during the first 30 years of my career in ophthalmology. Indeed, except for the introduction of intravitreal anti-vascular endothelial growth factor injections, there have been no spectacular advancements in ophthalmology since then.

I observed, during those first 30 years, the birth of the IOL,the introduction of phaco-emulsification techniques and the use of lasers in the treatment of eye diseases and in refractive eye surgery. Vitreoretinal surgery has boomed and modern eye examination methods (OCT, retinal scans, topographic modelling) have improved and now help in making better diagnoses.

During my first years in ophthalmology, we worked with a head loupe(with a 6x magnification) and had to open the eye for cataract surgery with a von Graefeknife over 145°, remove the cataract with forceps and close the corneal wound with eight 6-0 silk sutures. The patient stayed in hospital for 5 days and recuperation of normal vision, after removal of the stitches and prescription of the very high hyperopic lens, took 7 weeks.

Thedevelopment of the artificial IOL—first implanted by the late Sir Harold Ridley at St Thomas’ Hospital in London in February 1950—changed the course of cataract surgery. However, it took several years before Ridley’s invention became widely accepted; I performed my first lens implant in the late 1970s. Before then, it made no sense to perform unilateral cataract surgery.

Indeed, the obligatory use of the very disturbing postoperative aphakic correction was only supported when used bilaterally. These high hyperopic(+12 D)glasses caused a 25% magnification of the image, which was not supported when prescribed unilaterally. These ugly glasses were also responsible for the very annoying roving ring scotoma called the “jack in the box phenomenon,” which made driving a car a very risky business.

Only when contact lenses for the correction of aphakia were introduced, towards the end of the 1970s, did it make sense to operate unilaterally, as the contact lenses created a magnification of only 6–8% and this difference could be supported by the other phakic eye.

Once phacoemulsification became available, after the late Charlie Kelman’s discovery in 1967, the corneal opening needed only to be 5 mm and then, after the introduction of foldable implants, 3 mm. Stitches were no longer needed because a scleral tunnel approach was already in use before foldable lenses became available.

In 1987 I mastered the technique during a course given by Dr Jim Little, an associate of Kelman, in Geneva, Switzerland. At that time there were only four surgeons in Belgium using this method. I recall that in the United States some time later, a wet lab on pig and rabbit eyes was organised in the ballroom of the Hilton Hotel. One hour later, a wedding party was held in the same room!

IOLs improved progressively over time. Tinted and UV-coated lenses became available and, from around 1990, presbyopia-correcting lenses(bifocal, trifocal and so-called accommodative lenses) were introduced.

The evolution continued and I became involved in many studies on foldable IOLs (Tecnis) and presbyopia-correcting lenses, and lectured on them at European and American meetings. The most difficult part was selecting the right patient for the right lens.

The use of phakic IOL implantations in myopia and hyperopia became important in refractive surgery.Lenses included the Artisan lens, an iris-fixated lens first launched for cataract surgery and later also used for myopia and hyperopia correction in phakic eyes; the Verisyse IOL; and the Veriflex, which is the foldable IOL; all designed by Jan Worstfrom the early 1980s onwards.

The Artisanwas initially referred to as the “worst” lens and so this was a difficult one to promote! I used to perform the surgery bilaterally in one session under topical anaesthesia so that the patient immediately obtained an excellent result. These surgeries gave me the most satisfaction.

This technique, now used in every modern cataract surgery procedure, was unknown when I performed my first cataract surgeries. It was popularised simultaneously by Dr Howard Gimbel in Calgary, Alberta, Canada, and Prof. Thomas Neuhann in Munich, Germany, in 1983–1985, both of whom went on to publish their work in 1991.

I visited the two ophthalmologists, acquired the technique and have excellent memories of working with them during many American Academy of Ophthalmology (AAO) and American Society of Cataract and Refractive Surgery (ASCRS) courses.

The use of aburied corneal knot when stitching up corneal wounds was also unheard of when I started cataract surgery. This technique, whereby the corneal silk stitches knot is reversed and buried in the stroma, was introduced in France by Dr Jacques Charleux in the 1970s.

Before this, the surgeon had to cut the stitches very short so that they did not cause too much irritation, which is difficult to imagine. Of course, nowadays, in most cataract surgeries the incision is so small that stitches are unnecessary.

Cataract surgery in a freestanding centrewas undertaken for the first time in Arizona, US, in the 1970s, being unknown in Europe at that time.Of course I wanted to apply these new approaches in my practice: in 1984 I realised the first cataract surgery on an outpatient basis in the Benelux region (Belgium-Netherlands-Luxemburg) in my clinic in Antwerp.

Nowadays, a maximum error of 0.25 in the outcome of IOL power calculation seems achievable, but this was not always so. Ridley’s first two cases resulted in an important postoperative refractive error because the refractive power of the material used was unknown and the importance of eye-length measurement had still to be discovered.

IOL power calculation formulas were progressively developed and improved. As American ophthalmologist Prof. Jack Holladay once said, surgeons have the best outcomes with their own formulas.

Measurement techniques have improved spectacularly from the starting point of a contact method that used A-scan biometry, applying a contact probe on the eye with the risk of causing an eye deformity, implementing anatomical instead of optical biometry and creating inaccuracies.

At Ghent University in the late 1970s, together with Dr Roger Allewaert, we developed one of the first optical biometry calculation programs. Optical biometry using the Zeiss IOL master appeared in the late 1990s and I later became involved in teaching many courses on this subject.

When I started working in ophthalmology there were no important congresses in Europe, although there were a few very famous professors working in France, Germany, Italy and Belgium. Meetings were more social gatherings than scientific sessions; wet lab and video courses were non-existent and those interested in learning about the latest developments in ophthalmology and meeting pioneers in the field had to visit the US and attend the AAO or the ACS (later ASCRS) meeting.

It was in the US that I learned about outpatient cataract surgery, radial keratotomy, lens implants and phaco surgery, as well as peribulbar(Drs David Davis and Mark Mandel, 1985) and, later, topical anaesthesia (Dr Richard A. Fichman, 1991). The European congresses(for example, European Society of Ophthalmology and European Society of Cataract and Refractive Surgeons) gradually became more important and began to compete successfully with the American congresses.

Botulinum toxin for the treatment of strabismus was introduced by the late Alan Scott in 1973. When I started using botulinum toxin type A for the treatment of blepharospasm in 1980, the condition was still considered a psychiatric disease. At that time I had no idea that this treatment would become so widespread for so many other medical conditions as well as for cosmetic reasons.

After I had met Scott at one of the AAO meetings, I was able to order the product overseas. It was delivered in a protected lead container because one such a shipment could have killed a huge proportion of the citizens of Antwerp! The dry product was dissolved, diluted one million times and made ready for injection by our pharmacist.

The product received US Food and Drug Administration (FDA) approval for strabismus and blepharospasm in 1989, and in 2002 it received FDA approval for the cosmetic applications as ‘Botox’ (Allergan).

In 1970, Svyatoslav Nikolayevich Fyodorov (1927–2000), a surgicalpioneer, wasthe first to discover that the curvature of the cornea, and consequently its refractive power, changed after it had been perforated by a traumatic impact.This was the start of radial keratotomy whereby 8–16 or sometimes 32 radial incisions were used to flatten the cornea, reducing myopia. This treatment was brought to the US by Leo Bores in the late 1970s.

I attended some courses during weekends in the US, then flew back to Europe and started practising the technique, but first I tested the extremely sharp diamond knife on rabbit eyes. I incised their corneas then placed the rabbits in my mother’s garden and checked on them the next morning.

I found that they were happilyjumping around and eating as if nothing had happened. This was proof for me that I had mastered the technique and could start operating on human patients.

In 1985, I became acquainted with the first application of the excimer laser for refractive surgery. Eight European surgeons attended a session in Wangen, Germany, whereit was demonstrated how the excimer laser (MEL 50) could improve the making of radial incisions.

Dr Stephen Trokel, who is regarded as being the first ophthalmologist to recognise the significance of the excimer laser for use in corneal refractive surgery,was present.He had flown in that morning and was extremely tired, falling asleep during the evening dinner.

We later realised that the incision approach was not the right one and that removing part of the cornea was a much better way. In 1992,after a European meeting in Brussels, I organised the first live refractive laser surgery with an excimer laser.

This had never been done before anywhere in the world, but I did not realise that until later. Nearly all European and many American surgeons who were later to become famous in the discipline of laser refractive surgery were in attendance. Together with Prof. Dieter Dausch and some pioneers of excimer laser refractive surgery (members of the Carl Zeiss Academy), and later on Prof. Dan Reinstein, we lectured worldwide on the use of the excimer laser in ophthalmic refractive surgery.

At first we used the rather brutal technique of PRK, whereby the corneal epithelium was removed before the application of the laser. Healing took 3 days and was very painful. The use of a bandage contact lens relieved the pain and the switch to LASIK made it possible to treat both eyes in the same session and practically without pain. Later on, the femtosecond laser was introduced in my eye centre.

I was fortunate to have been involved in the first discussions, at the Zeiss Academy group in Barcelona, Spain, in 2008, where the idea of femtosecond lenticule extraction with a flap (FLEx) and, later on, SMILE was developed. “Mr SMILE,” Prof. Walter Sekundo, was at the forefront of this development.

Nobody at that time could have foreseen that refractive laser eye surgery would become the second most-performed surgery on the human body, after cataract surgery.

Other lasers (argon and krypton lasers) featured in ophthalmic treatmentfrom 1970 onwards. Specifically, the introduction of the Nd-YAG laser after 1980 created a revolution in the treatment of posterior capsule opacification.Until then, this complication had had to be treated by a surgical incision of the opacified capsule.

My ultimate hope is that my colleagues experience still more improvements in the beautiful discipline of ophthalmology and that all patients have the possibility of accessing timely and speedy access to the eyecare they need.

Dr Goes is the founder of the Goes Eye Center in Antwerp, Belgium (www.drgoes.be), and is still active as a consultant at the centre. He has no relevant financial disclosures.

Dr Goes reflects on a life at the forefront of ophthalmology, considering advancements in technology and the knowledge that has changed his practice and improved outcomes for patients.

Half a century of developments in ophthalmology: One doctor’s reflections

Cosmetic iris implants pose serious risks and are strongly discouraged, according to Dr Jorge Alio and Dr Francesco D’Oria, both from Vissum Alicante Miranza Group and the Miguel Hernández University of Elche in Alicante, Spain. However, despite the potential risks, the surgeries are still performed.

The currently available models are the NewColorIris (Kahn Medical Devices) and BrightOcular (Stellar Devices). The NewColorIris, a silicone iris diaphragm with six rounded flaps in the periphery to hold the device in place, has a diameter that ranges from 11 to 13 mm and a pupillary aperture of 3.5 mm and thickness of 0.16 mm. The BrightOcular, which is held in the eye by five triangular flaps in the periphery, comes with diameters ranging from 11.5 to 13.5 mm and thicknesses of 0.16 and 0.18 mm; the authors reported that the posterior face has grooves to facilitate aqueous flow.

Dr Alio and Dr D’Oria conducted a retrospective study of the medical records of five patients (10 eyes; age range, 27–46 years) who had received one of the devices (two with NewColorIris and eight with BrightOcular). The patients had been referred to the Vissum Instituto Oftalmológico de Alicante for complications associated with the latest models of the implants, which had been available for 6 years.

The authors reported that all the devices had been explanted 1–60 months after the surgeries (Figures 1 and 2). The mean endothelial cells density was 848 ± 227.5 cells/mm

. Corneal transplantations had to be performed in 30% of eyes; in other words, two eyes had a Descemet membrane endothelial keratoplasty and one eye had a penetrating keratoplasty.

Three other patients were advised that they would need a corneal transplant. Nine of the 10 eyes developed ocular hypertension and a filtrating surgery was needed in two cases. Early development of cataract was a common complication, with 40% of the patients—who were a mean age of 36 years—requiring cataract surgery.

A representative case was that of a 37-year-old woman who had a cosmetic iris implanted in both eyes and returned 2 years later with problems in her left eye. This patient had a dramatic endothelial cell loss of 1,163 cells/mm

Following referral, iris atrophy was seen superiorly. The investigators said that the endothelial cell density was relatively conserved after explantation, at 1,054 cells/mm

. The cosmetic implant of the other eye also had to be removed for similar reasons.

Neither of these commercial devices had been approved by the United States Food and Drug Administration or received a CE mark, but they continued to be implanted. Newer models have not been improved and cause the same complications to develop as the previous models.

“Patients with cosmetic iris implants have a high risk of definitive loss of vision and other serious complications that should be described to patients before implantation,” Dr Alio concluded. “Implantation of cosmetic [iris] implants should be considered today as malpractice in the light of available evidence.”

This article is adapted from Dr Alio and Dr D’Oria’s presentation at the 2021 American Academy of Ophthalmology annual meeting in New Orleans, Louisiana, United States. Dr Alio and Dr D’Oria have no financial interest in this subject matter.

Authors of a retrospective study into complications associated with iris implants advise that the procedure should be considered as malpractice.

Cosmetic iris implants pose high risk of vision loss

The greatest likelihood of a germline mutation in patients with a unilateral retinoblastoma occurred in patients who were 1 year or younger versus those older than 1 year, as well as in a subset of patients 3 months and younger versus those between 3 and 12 months of age. This finding was presented by Dr Carol Shields, chief of the Ocular Oncology Service at Wills Eye Hospital in Philadelphia, Pennsylvania, United States.

Dr Shields and her colleagues conducted a retrospective case series to evaluate the likelihood of germline retinoblastoma in children with solitary unilateral retinoblastoma. She explained that the goal of the study was to determine the risk of patients developing more of these tumours—that is, the risk for a germline mutation.

“It is important to know the germline status because the patients are at risk of developing multiple bilateral retinoblastomas, pinealoblastoma and secondary cancers,” Dr Shields said. “These can lead to blindness and death.”

The investigators retrospectively reviewed 482 consecutive patients who presented with one unilateral retinoblastoma and were later found to have a likely germline tumour. The latter was defined as a family history of retinoblastoma; development of bilateral disease and/or new tumours; and the gold standard: i.e., a documented germline on genetic testing.

A comparative analysis was then completed based on the following patient age groups: 0–1 year; 1–2 years; 2–3 years; and older than 3 years. The results showed that in children aged 0–1 year who presented with one unilateral retinoblastoma, 29% had a germline mutation (odds ratio 2.96). When compared with children older than 3 years, 9% had a germline mutation. This difference reached significance (

Among children who were 12 months or younger with one unilateral retinoblastoma, Dr Shields reported that in the youngest of these children (aged 0–3 months), 61% had a germline mutation. When these children were compared with those aged 9–12 months, the percentage dropped to 22% with a germline mutation. This difference was significant (

“It is clear that the youngest children with a unilateral retinoblastoma are at the greatest risk for a germline mutation,” Dr Shields said. In the other age groups—aged 3–6 months, 6–9 months, 12–24 months, 24–36 months and older than 36 months—the respective percentage of germline mutations was 20%, 24%, 17%, 8% and 9%.

“Of the 482 consecutive patients with a solitary unilateral retinoblastoma who were seen on the Ocular Oncology Service at the Wills Eye Hospital, we found a significant decreasing risk for a germline mutation based on the older patient age at presentation,” Dr Shields concluded.

This article is adapted from Dr Shields’ presentation at the American Academy of Ophthalmology 2021 annual meeting. This presentation received the Best Poster award. Dr Shields has no financial disclosures relevant to this topic.

In one study of children with solitary unilateral retinoblastoma, the youngest children were found to have the greatest risk for a germline mutation.

Ophthalmology Times Europe May 2022