Cataract Surgery: Evaluating Evolving Technologies

Casanova spent as much time in European prisons as he did in the arms of Venetian beauties and it is here that the idea of the intraocular lens (IOL) took life. Casanova, hearing of the concept of placing glass spheres into the eye after cataract extraction from Italian Oculist, Tadini, passed this idea to Casaamata (another oculist) who was Casanova’s prison guard in Dresden. Glass sphere implantation failed as it fell to the bottom of the eye, but the concept was good. The application of technology to cataract surgery and lens implantation has made this one of the most successful prosthetic procedures in modern medicine.

Opacification of the crystalline lens occurs as the lens proteins (crystallins) manifest altered morphology due to biochemical insult

Cataract – to the Greeks, known as falling water (Kataraktes); to the Latins as an extravasation and coagulation of humors behind the iris suffusion, and to the Arabas, as white water. It is the same condition whatever the name, and completely curable. The oldest documented case of cataract dates back more than 4,000 years and was seen in the eye of an Egyptian statue (Figure 1). Surgery for cataract has a similar known history, with a representation of couching, a procedure where the cataractous lens is displaced out of the visual axis using a long sharp instrument plunged into the eye, observed in Egypt around 1200BC (Figure 2).

Couching is, in fact, one of the oldest surgical procedures. It was first described in Indian texts in 800BC, though it may have originated in Babylonia or Egypt. Couching sometimes restored vision but was a very ineffective and dangerous technique where the complications often outweighed any benefit to vision. Sadly, it is still performed as treatment for cataract in countries such as Yemen.

Cataract extraction was probably introduced in the 2nd century using suction instruments (a straw) powered by human lungs. It was better that the cataractous lens was removed from the eye to clear the visual axis. A form of extracapsular cataract extraction surgery was performed by Daviel in 1774 though it may date back as far as 600BC to an Indian surgeon who partially removed lens matter through a small scleral incision.¹ This concept of lens removal remains valid today, though it was the introduction of IOL implants that made cataract surgery the successful operation we will discuss here.

Sir Harold Ridley was responsible for the introduction of the modern IOL implant in the mid-20th century. It took quarter of a century for the ophthalmic community to truly embrace the idea, but lens implantation is now the standard, and modern lens designs enable the visual outcomes we take for granted after cataract surgery.

Cataract is a universally important cause of visual impairment and blindness. Typically, cataract occurs with ageing but is a complex disorder with environmental and genetic risk factors. Despite surgical intervention, it remains a leading cause of global visual impairment, accounting for 51% of the world’s blind and 33% of visual impairment.² The treatment of cataract is surgery, with more than 20 million procedures performed each year. Surgery is effective and efficient but not universally accessible, so it’s worth considering non- surgical management of cataract before we delve into the technology delivering modern cataract surgery.

despite its advanced technology, femtosecond laser was not superior to phacoemulsification in cataract surgery and, with higher costs, did not provide an additional benefit over phacoemulsification surgery

DRUG BASED TREATMENTS

At present there is no effective pharmacological treatment for cataract. Drug based treatments aim to retard, prevent or reverse cataract formation by targeting structural maintenance and minimising oxidative damage. Delayed lens opacification will reduce morbidity and the cost of health care. It is estimated that delaying the onset of significant cataract by one decade will reduce surgery and associated costs by 50%.³

Many agents have been purported to have anti-cataract properties, but few stand up to scientific review. Drugs such as Pirenoxine (Catalin) are commercially available and, while they have theoretical anti-cataractous properties by binding with Ca2+ and selenite (two inducers of cataract), there is no robust clinical trial data to support their efficacy.

Categories of Possible Anti-cataract Drugs 

and aspirin-like drugs – the exact mechanism of action in preventing cataract is not clear and may be as simple as enhanced blood flow, allowing more antioxidants to enter the aqueous or more complex protection against structural changes or oxidative damage. The required large systemic doses and absence of a known topical form of aspirin limit its application (Figure 3).

Protein stabilisers/ inhibitors of protein aggregation – Bendazac is commercially available for use as an anti-cataract treatment in Argentina, Korea and some European countries. A small placebo controlled trial demonstrated Bendazac, given orally, to be effective at improving visual acuity and lens opacity.⁴

Growth factor antagonists – Naltrexone, an opioid growth factor receptor antagonist, can enhance corneal reepithelialisation, treat dry eye, enhance corneal wound healing, and may have a role in preventing cataract through enhanced activity of the lens epithelium.

Antioxidants – exogenous antioxidants have been shown to significantly protect against cataract in a rat eye model.⁵ Various antioxidants exhibit a protective effect through scavenging free radicals and preventing oxidative lens damage in lens culture models. The challenge with oral antioxidant therapy in the prevention of cataract is getting enough drug to the target tissue in the lens nucleus. Results with oral antioxidant treatment are inconclusive and research is now directed at topical delivery systems, such as thermal gels, pH sensitive gels, and self-nanoemulsifying systems that enhance penetration and target tissue concentrations.

GENETICS

We are a long way from fully understanding the genetic basis for cataract. Age-related cataract is a multifactorial condition involving interaction between environmental factors (e.g. UV light and tobacco smoking) and genetic predisposition. Heritability contribution to age-related cataract ranges from 35% to 48% for nuclear opacity, and 24% to 58% for cortical opacity.⁶ The exact nature of the underlying genetic factors is poorly characterised. Gene therapy is not considered as an intervention for cataract development.

STEM CELLS

Cataract surgery is a two-step procedure, with removal of the opaque crystalline lens and implantation of a new artificial IOL. An artificial, synthetic lens presents particular challenges after surgery and it is appealing to have a regrown human lens using stem cell regeneration. Stem cell research, using enhanced endogenous stem cell populations, has successfully regrown the crystalline lens in infant cataract surgery.⁷ Here, the technique for removal of the crystalline lens was modified by minimising the size of the anterior capsulorhexis and moving it peripherally off the visual axis so as to preserve the central lens epithelial cells lining the anterior capsule. A biconvex, transparent and accommodating lens grew with appropriate dioptric power. The application of these concepts and those of researchers, such as Michael O’Connor at Western Sydney University where they have grown light focusing human lenses in vitro from pluripotent stem cells, may eventually make the artificial lens implant redundant, but not yet.⁸

Cataract becomes a problem when it precludes clear vision by obstructing the visual axis. Opacification of the crystalline lens occurs as the lens proteins (crystallins) manifest altered morphology due to biochemical insult. Treatment aims to remove the obstruction from the visual axis and restore focusing through implantation of an artificial lens.

The patient’s experience of cataract surgery is as much about comfort, confidence and convenience, as the outcome from the surgery itself

LENS REMOVAL

Lens extraction using extracapsular surgery (ECCE) was widely used from the mid-1700s for about 100 years when intracapsular surgery (ICCE) came into vogue. Extracapsular surgery allows expression of the cataractous lens from the capsular bag, thus preserving the posterior capsule – an important anatomic layer of separation in the eye. Early extracapsular surgery involved a large corneal incision – larger than 10mm, puncturing of the anterior lens capsule, expression of the nucleus, and curettage of the cortex. Extracapsular surgery was limited by the absence of technology and it was the introduction of operating microscopes in the 1970s that saw a re-emergence of capsule

preserving surgery as the preferred intervention.

ICCE is removal of the whole lens, with its capsule, through a large limbal incision (Figure 4). The lens zonules were initially disrupted manually, either with a surgeon’s finger or using forceps. Barraquer introduced the use of a lytic enzyme (Chymotrypsin) to dissolve the lens zonules in 1957. The most modern form of ICCE uses a cryo probe to freeze the lens – zonule complex – and remove the cataract from the eye. Intrinsic in the procedure of ICCE is the large wound required to deliver the whole lens and the loss of the posterior capsule. ICCE fell from favour due the presence of frequent sight limiting complications. Extracapsular surgery continues to be used and manual small incision cataract surgery (MSICS) is the mainstay of cataract management in less wealthy countries.

Most cataract surgery today uses the technique of phacoemulsification as developed by the saxophone playing ophthalmologist, Charles Kelman, in 1967. This technique uses ultrasonic energy to emulsify the cataractous lens, allowing it to be removed as an emulsion through a small incision. The benefits of the small incision are a controlled environment during surgery and a more stable eye afterwards, with faster visual rehabilitation. The full benefits of small incision surgery had to wait until foldable IOLs were introduced.

Current phacoemulsification cataract surgery is day surgery. Mydriatic drops dilate the pupil and topical anaesthetic is used. A sterile field is created using antiseptic solution and drapes, and the eyelids are held open with a speculum. An operating microscope is positioned, and surgery begins with two entry wounds into the anterior chamber. A viscoelastic is instilled to fill the anterior chamber, protecting the corneal endothelium and maintaining the shape of the eye as the aqueous egresses. A continuous circular opening is created in the anterior capsule, using forceps, which gives access to the lens. Hydro dissection separates the lens from the capsular bag and the phacoemulsification instrument then emulsifies the lens nucleus, allowing it to be aspirated from the eye. The phacoemulsification handpiece has three elements with an ultrasonic driven mechanical lens fragmenter, irrigation and aspiration. Cortical debris is aspirated and a lens is placed into the capsular bag. All modern cataract surgery is a refinement and variation on these elements.

KEY TECHNOLOGIES

Some key technologies that are applied to modern cataract surgery are:

• Femtosecond laser,
• Digital operating microscope,
• Intraocular lens – optical and material design, and
• Pharmaceuticals.

Is Laser Assisted Cataract Surgery Worth the Money? 

Femtosecond laser technology has been applied to cataract surgery, allowing the creation of corneal wounds, capsulorhexis and cataract breakup using computer guided laser energy under image control. As a more predictable intervention, we need to evaluate the safety of the procedure – is there any downside apart from cost – and the benefits.

Femtosecond laser assisted cataract surgery (FLACS) promises safer surgery with fewer complications and better refractive outcomes. Early adopters seemed compelled to talk it up and justify the extra cost to patients with literature that was replete with opinion and conclusions that did not match the data. While an exciting technology that appeals to patients and doctors alike, the data is inconclusive. A recently published, elegantly conducted trial comparing FLACS with phacoemulsification cataract surgery concluded that “despite its advanced technology, femtosecond laser was not superior to phacoemulsification in cataract surgery and, with higher costs, did not provide an additional benefit over phacoemulsification surgery”.⁹

A larger cohort study involving nine European countries and Australia compared 2,814 FLACS with 4,987 manual cataract procedures looking at visual, refractive and adverse outcomes. Again, the authors concluded that FLACS did not yield better visual or refractive outcomes with intraoperative complications being similar (and low) in both groups. Postoperative complications were more common in the FLACS group.¹⁰

FLACS allows cataract removal with less phacoemulsification energy in the eye. This may be expected to minimise damage to the corneal endothelium, making it a safer procedure long term. Confusingly, this is not clear; a recent publication showed significantly less endothelial cell loss (ECL) for FLACS as compared with standard phaco surgery. In this study a significant association between phaco energy and ECL was demonstrated with more phaco energy used in non FLACS cases.^11,12 An earlier well respected Australian paper showed a different outcome, with FLACS patients showing greater ECL when FLACS was used to create the corneal wounds.^13,14 What we can say is that more phaco energy causes more damage to the endothelium and that when FLACS is used for capsulorhexis and lens division, but not corneal incisions, there is less damage to endothelium.

Despite the absence of statistically significant benefits overall, there is merit in automating surgical procedures, thus reducing the possibility for error, and there is a place for FLACS – though it is by no means essential for most patients. There are situations where FLACS is preferable, offering individual patients improved outcomes. When a perfect capsulorhexis, aligned with the visual axis, is needed for attachment of modern IOLs, such as Femtis15,16 (Figure 5), the femtosecond laser brings accuracy that cannot be reproduced with manual techniques.

Alternate Methods for Creating the Capsulorhexis 

A good capsulorhexis is key to the refractive outcome after lens implant surgery – or is it? A continuous circular capsular opening (rather than a can opener) gives a more stable and predictable lens position with consequent better refractive outcomes¹⁷ but it is less certain that the exact size and circularity of the capsulorhexis matters for most IOLs. FLACS produces a consistently perfect capsulorhexis of predictable size and circularity that is not possible with manual techniques (Figure 6). This looks better (Figure 7), but it has not been shown to give better refractive results than manual phaco surgery. Having the capsulorhexis completely overlapping the optic edge does give better control of lens tilt and less induced astigmatism.¹⁸ Importantly, the capsular opening created with the femtosecond laser may be weaker than when created either manually or with other techniques. Intrinsic in the use of femtosecond lasers to ‘cut’ tissue, is an irregular cut surface as thousands of perforations are created and then torn like a postage stamp edge. This leaves multiple weak points that may (rarely) result in tearing of the anterior capsulorhexis.

Femtosecond laser cataract surgery has demonstrated that it is possible to create a predictable and precise capsulorhexis. This will be increasingly important as newer lens technologies, that are dependent on a perfectly aligned capsulorhexis, are coming to market.

Zepto offers a simple automated capsulorhexis using a disposable intraocular surgical hand piece. A flexible metal ring is held against the anterior capsule using suction, and rapid electrical pulses create a phase transition in water molecules that result in mechanical cleave of the capsule (Figure 8). The Zepto device creates a precise, circular 5.2mm capsulorhexis as part of the normal surgical flow, and is less expensive than a femtosecond laser. While Zepto has gained popularity due to its surgical efficiency and lower cost than FLACS, there are limitations associated with the mechanical aspects of the device, with cases of failed capsulorhexis, iris entanglement, and anterior chamber damage due to suction malfunctions.¹⁹

Capsulaser is a selective laser that creates a circular capsulotomy using a continuous laser pulse rather than multiple separate pulses, as with FLACS. The laser is a small module that becomes part of the operating microscope so patient flow and surgery ergonomics are optimised. The patient is positioned under the operating microscope and a capsule staining dye is injected into the anterior chamber. The dye (Trypan Blue) sensitises the capsule to laser energy, allowing for selective capsulotomy. Laser energy is delivered as a single pulse via a lens held against the cornea. Capsulaser has the benefits of being cost effective, ergonomically efficient, and clinically beneficial, creating a capsulorhexis opening that is almost three times stronger than that created with the femtosecond laser. The cut edge of the anterior capsule has a smooth rolled appearance with dense amorphous collagen. This is more stretchable and resists tearing better than the perforated cut edge seen with femtosecond laser cutting. The seminal paper comparing capsulorhexis quality with manual, femtosecond and selective laser capsulotomy,²⁰ quantified tear resistance and stretchability, and used electron microscopy to show the edge quality for each technique. The selective laser rhexis was 1.5 times stronger than manual capsulorhexis, which was in turn, 1.3 times stronger than the femtosecond laser microperforated capsular cut (Figure 9).

Digital Imaging and Guidance Systems 

Digitisation of the operating microscope adds the next level of sophistication to intraocular surgery. The introduction of operating microscopes in 1970 was key to modern cataract surgery, with more intricate and detailed manoeuvres becoming possible. Intracapsular cataract removal was replaced by extracapsular, and then phacoemulsification surgery.

Zeiss and Alcon have commercially available digital operating microscopes. The Zeiss system uses two offset high definition cameras incorporated into the optics to produce a stereoscopic 3D image on a 4K monitor (Figure 10). Surgery is performed while viewing the screen (rather than through microscope eyepieces) with better ergonomics, improved depth of field, and reduced light illumination required. (The Zeiss system allows for use of the standard microscope eyepieces or the digital imaging system.) A digital imaging system allows the display of data (such as real time optical coherence tomography information) overlaid on the operating field. Price would seem to be the only barrier to widespread adoption of this superior technology.

Painless, Dropless Cataract Surgery 

The patient’s experience of cataract surgery is as much about comfort, confidence and convenience, as the outcome from the surgery itself. Painless surgery involves anaesthesia but also minimal discomfort from drops, injections and extra interventions. There are a number of therapeutic advances that have facilitated a safer and more comfortable cataract procedure.

Anaesthesia – cataract surgery is mostly performed with local anaesthetic only. General anaesthesia is not indicated, and rarely needed – topical anaesthesia is typically all that is required. The patient’s experience is enhanced through minimisation of drops on the eye that are associated with discomfort, inconvenience and non-compliance. Before surgery, the anaesthetic and dilating drops can involve the patient having 10 or more drops into the eye before surgery even commences. We now use a compounded gel that contains mydriatic and anaesthetic agents requiring a single application into the eye which is then taped shut until surgery.

No drop cataract surgery – post-surgery, antibiotic and inflammatory drops are used for several weeks. Drops four times a day is a big ask for patients and can damage the ocular surface, exacerbating ocular surface disease. Compliance and efficacy of administration are poor with our existing post-operative drop regimes, with as few as 8% of patients getting the medication as intended.²¹ Research has progressed into no drop and reduced drop regimes for post-operative cataract surgery patients.

Transzonular injection is a drug delivery system that may obviate the need for post-operative eye drops. The technique was introduced in the United States of America with more than 80,000 procedures having been performed.²² Reported efficacy was equivalent to topical treatment for inflammation.²³ An injection of Moxifloxacin and Triamcinalone (TriMoxi) is given using a blunt 27g canula passed around the edge of the capsular bag between the zonules into the anterior vitreous. Use of this Moxifloxacin/ Triamcinolone regime obviates compliance issues and is convenient for patients, with only 5% requiring additional topical drops for breakthrough inflammation.²⁴ This is a novel technique with the potential downsides of retinal detachment and vitreous haemorrhage (though these have not been reported) and cloudy vision (Figure 11) for a few days due to the Triamcinolone. Substituting Dexamethasone avoids this but has a higher likelihood of giving a steroid pressure response.

Reservoir based drug delivery systems are another approach to dropless cataract surgery. Dexamethasone preparations are used as a spherical drug impregnated matrix placed into the anterior chamber under the iris at the end of surgery, or as a rod like hydrogel implant placed into the inferior canaliculus. Depot steroids should be avoided in steroid responders. Punctal plug delivery systems are also in trial for antibiotic delivery. Polyactiva (an Australian product) is a biodegradable punctal implant that elutes Levofloxacin over 30 days.

THE INTRAOCULAR LENS

Lens implants are at the core of successful cataract surgery, with lenses now allowing a full range of visual function. With toric, trifocal, extended depth of focus (EDOF) and monofocal EDOF lenses, there is too much to cover here, but take a look at our article from July 2020 in mivision (www. mivision.com.au/2020/07/omnifocalitythe- holy-grail-for-cataract-surgery).

So, what does the modern high-tech cataract operation look like today in the real world?

In a nutshell:

• Enhanced pre-op planning with lens power calculations, knowledge of pre-existing ocular conditions using aberrometry and corneal topography, ocular surface disease management using tools such as tear osmolarity, and putting the patient in control of lens choice.
• Painless surgery with sedation and topical anaesthesia that takes 10 minutes using high definition optical operating microscopes.
• Selective use of laser assisted cataract surgery as dictated by patient comfort, need and lens choice.
• Digital alignment and lens positioning with systems such as Verion (Alcon) and Calisto (Zeiss).
• Post-operative control of inflammation and infection using a combination of intrasurgical and topical medications.

Safe and predictable surgery with modern lens design makes possible excellent visual outcomes. The continued application of new technologies will see incremental, rather than dramatic, improvements to patient convenience, comfort and vision.

Dr Patrick Versace is a cataract and refractive surgeon in both private and public hospital practice in Sydney, Australia. He holds a position at the Prince of Wales/ Sydney Eye Hospital where he is involved in registrar surgery training and also a position as Senior Lecturer at the University of New South Wales. Dr Versace consults at Bondi Junction in Sydney. 

To earn your CPD points from this article visit mieducation.com/cataract-surgery-evaluatingevolving- technologies 

References 

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