PCO AND THE PREMIUM LENS

Whenever it appears, posterior capsular opacification (PCO) that would be visually insignificant with monofocal lenses can wreak havoc with diffractive multifocal optics. So much so that Matteo Piovella MD, Monza, Italy, reports that about half his multifocal patients experience significant loss of near vision due to mild PCO within six months of implantation. He believes that PCO-related forward light scatter and the resulting loss of visual acuity and contrast sensitivity become intolerable more quickly with multifocal lenses because they already push the limits of acceptable vision quality.

[caption id='attachment_1938' align='aligncenter' width='500' caption='Image shows schematics of the customisation procedure in LALs'][/caption]

David Spalton FRCS, FRCP, FRCOphth, of St Thomas’ Hospital, London, UK, agrees. Diffractive lenses such as Alcon’s ReSTOR lose up to 20 per cent of incoming light and split what remains, leaving as little as 40 per cent available at near and far focal points, he notes. Some newer designs, such as the PhysIOL FineVision trifocal lose less, but still reduce contrast sensitivity.

“With multifocal diffractive lenses, even very small amounts of PCO can have a very damaging effect on patients’ functional vision.â€

Dr Piovella’s usual solution is early YAG capsulotomy. “At first the decision was difficult. If the patient was not happy with the lens, the choices were YAG laser or lens exchange. If the YAG doesn’t work, changing the lens with the posterior capsule open is much more dangerous and difficult.â€

But as he gained experience, he learned that in most cases a YAG capsulotomy greatly improves near vision, and almost all patients are satisfied with it.

However, YAG capsulotomy does carry risk. It can produce permanent floaters and, rarely, retinal tears or detachments. It may also contribute to lens tilt or decentration, which also creates problems for diffractive multifocals, though Dr Piovella says he has not experienced this.

Because of light loss, multifocal IOLs are also contraindicated in patients who have or are at risk of developing maculopathy, Dr Piovella says. For these patients, and for patients who want to avoid glare and haloes at night, accommodating designs may be a better premium lens choice – though these patients must be counselled that they may need spectacles to read fine print, he says.

But while currently available accommodating IOLs are not as affected by small amounts of PCO, their function is vulnerable to other problems related to lens epithelial cell growth, says Liliana Werner MD, PhD, of the University of Utah, Salt Lake City, US.

“Any remaining anterior LECs in contact with the IOL have the potential to undergo fibrous proliferation; thus anterior capsule opacification is essentially a fibrotic entity. Capsular fibrosis is particularly problematic for ‘accommodating’ IOLs designed to move within the bag.â€

Open-capsule designs are

promising Post-mortem research shows that lenses with larger areas in contact with the anterior capsule, particularly silicone plate-haptic designs, are more prone to fibrosis and anterior capsule opacification (ACO), Dr Werner notes. Conversely, lenses that hold the anterior capsule edge away from the lens surface, such as the dual-optic Visiogen/AMO Synchrony, and lenses that expand the capsular bag without touching either anterior or posterior capsules, have been shown to prevent PCO and ACO in animal models. Subsequent clinical studies have confirmed low PCO rates with the Synchrony, she adds. Other designs, such as the disk-shaped lens manufactured by Anew Optics are under pre-clinical evaluation.

[caption id='attachment_1939' align='aligncenter' width='500' caption='Before and after YAG laser treatment'][/caption]

That finding mirrors Dr Piovella’s early Synchrony experience. Of 32 patients implanted, only two, or about six per cent, have required a YAG capsulotomy in the first year, he says. In addition to lower PC occurrence, the lens also has the advantage of providing contrast sensitivity on a par with a monofocal lens, he adds.

[caption id='attachment_1940' align='aligncenter' width='500' caption='Synchrony channels provide aqueous circulation in the bag avoiding PCO'][/caption]

In Synchrony clinical trials conducted for Visiogen, George Beiko MD of the University of Toronto, Canada, observed no PCO develop when the lens was placed in eyes with pristine capsular bags that were polished and free of epithelial cells or fibrosis. When placed in younger patients with a fibrous subcapsular component to the posterior capsular bag, the remnant PCO did not increase during the observation period. “I have some thoughts as to why this may be happening but no real explanation. So yes, PCO seems to be less of an issue with dual-optic IOLs.â€

One possible mechanism for discouraging PCO may be compression of the bag, and perhaps residual lens epithelial cells as well, Dr Werner says. Mechanical stretch of the bag at the equator by devices such as the capsular bending ring of Nishi and Menapace, and Hara’s equator ring is another potential PCO-discouraging mechanism, she adds.

Ioannis G Pallikaris MD, PhD of the University of Crete, Greece, having developed the Peripheral Capsule Reconstructor (i-PCR), believes that an expandable ring device, which has the same anatomical shape with the peripheral capsule, and mimics the peripheral lens features, may avoid the PCO and at the same time can be used as a centration device for any type of IOL. In 18 patients with 20 months’ follow-up, no PCO has been observed in the posterior capsule, he said.

Constant irrigation of the capsular bag inner compartment by the aqueous humour could be another factor discouraging epithelial cell proliferation, Dr Werner says. Aqueous humour irrigation would help explain the PCO preventative effect even in eyes where there was no contact between the optic of a disk-shaped IOL under investigation and the posterior capsule. This hypothesis is bolstered by reports that TGF-β2 in the normal aqueous humour inhibits proliferation of both lens epithelial and corneal endothelial cells. According to Nishi, constant irrigation by the aqueous humour also may prevent cytokines that stimulate epithelial cell proliferation, such as interleukin-1, from reaching a threshold concentration, she notes. This finding is in line with Moran Eye Center research showing that a disk-shaped hydrophilic acrylic lens that avoided optic contact with the capsular bag showed less capsular bag opacification than a conventional hydrophobic acrylic lens contacting the posterior capsule in rabbit eyes, Dr Werner adds.

But modulating, rather than eradicating, lens epithelial cell growth may be the more desirable goal, Dr Spalton says. His research implanting IOLs into cultured post-mortem human capsular bags shows that fibrosis occurs when lens epithelial cells are left in the bag, but when they are all obliterated in the fellow eye, the implanted lens wobbles. This suggests that lens epithelial cell growth plays an important role in stabilising current lens designs, and that approaches such as destroying all epithelial cells with lasers or pharmaceuticals may be counterproductive.

Dr Spalton is now conducting a study of the impact of cytokine concentration on lens epithelial cells in a human capsular bag model. But while the evidence is preliminary, he believes that lens designs that allow aqueous circulation may be the key to controlling PCO. “I think we are coming into an era of open-bag lenses,†he says.

Accommodation trade-offs

While early results with the dual-optic lens look good for both vision quality and modulating PCO, the design does involve trade-offs, and questions remain about it. Chief among them is whether it actually accommodates by moving, and if so, can the effect be reliably replicated in clinical practice.

In controlled studies comparing the dual-optic lens with single-optic lenses designed to accommodate by moving, Dr Beiko has found that the dual-optic on average produced 20/20 uncorrected binocular visual acuity at near, intermediate and far distances, and provided a range of accommodation similar to patients with multifocal implants. The single-optic accommodating lens, though, had little effect on near vision when both eyes were targeted for plano distance vision, and provided no advantage in near vision compared with monofocal non-accommodating lenses targeting a similar amount of myopia.

Dr Beiko notes, however, that the dual-optic lens trials were conducted with healthy subjects, and the results cannot be extrapolated to the general cataract population, which includes a significant proportion of patients with other ocular pathology. For example, the lens would not be suitable for patients without intact capsules or zonular instability, though such patients may benefit from three-piece multifocals fixated to the iris or sclera.

Several reports at meetings have also shown the dual-optic lens moves under accommodative stimulation using ultrasound and other imaging technologies. However, objectively measuring dynamic accommodation would be required to fully clarify if these lenses are actually working, says Pablo Artal PhD, of the University of Murcia, Spain. Dr Spalton suspects that difficulties conclusively demonstrating dynamic accommodation could be delaying approval of the lens by the US FDA.

The bulk that may help the dual-optic lens combat PCO also comes with a trade-off – the latest version requires an incision of about 3.75mm for insertion, much larger that the 2.0mm or less for some competing multifocals. This raises the question of how much the greater surgically induced astigmatism that might accompany the larger incision might offset the advantages of lens’ otherwise superior optics compared with multifocal lenses.

Dr Beiko has found that the larger incision can induce up to 1.0 D of astigmatism, but the impact can be minimised by making the incision on the steep axis of the cornea and posterior to the limbus, he says.

“Patients tolerate up to 1.0 D of astigmatism, so there is minimal effect on visual performance. The gain in range of vision with a dual optic IOL far out ranks the minimal increase in astigmatism.â€

Dr Piovella reports similar results with 1.0 D being the largest amount of astigmatism induced in his dual-optic cases to date. He also points out that, as with PCO, multifocal diffractive lenses are affected much more by small amounts of corneal astigmatism than monofocal or accommodating lenses. One dioptre of cylinder typically results in two lines of lost vision with a multifocal compared with one line for the dual-optic lens, he says. Surgically induced astigmatism also tends to regress over time, and is manageable for even larger incisions. “I have huge experience since 1988 in performing phaco with implantation of 5.0mm rigid IOLs without significant induced astigmatism in over 90 per cent of the cases.'

Other accommodative approaches

Another fairly bulky accommodating lens on the horizon is PowerVision’s FluidVision. This lens uses contractions of the ciliary muscles to pump fluid in and out of its optic, which changes the lens’ shape and refractive power, much like the natural crystalline lens. It has achieved shape changes equivalent to accommodation of 5 D in unsighted patients, and is scheduled to enter clinical trials this year.

Pseudoaccommodative lens approaches also show promise. Prof Pallikaris reports achieving up to 2.5 D near accommodation with a hyperboloid IOL designed by the late Otto Wichterle and his collaborators at the Institute of Macromolecular Chemistry in Prague, Czech Republic. The rear surface of the hydrogel lens sits against the posterior capsule, which helps block PCO and may allow ciliary muscle contraction and pressure on the vitreous from external muscles to move the lens anteriorly, producing some true accommodation. The large aspheric optic also increases depth of field, facilitating near vision. The smooth surface extending all the way to the edge of the capsule eliminates glare and other dysphotopsias, Prof Pallikaris says. However, accommodative outcomes are not completely predictable and patients must be trained to make full use of the lens’ potential.

The Oculentis MPlus lens features an asymmetric refractive add zone similar to a bifocal in spectacles that transitions from near to far. While the design does split the image on the retina as other multifocals do, the smaller add zone minimises light loss and tends to localise glare compared with conventional symmetrical designs.

The end of PCO?

[caption id='attachment_1941' align='alignright' width='400' caption='Gross photographs of the disk-shaped lens manufactured by Anew Optics (under pre-clinical evaluation at the Moran Eye Center)'][/caption]

Another concept for eliminating PCO altogether is the bag-in-lens design pioneered by Marie Jose Tassignon MD of the University Hospital of Antwerp, Belgium. The lens features a grooved circular haptic and is implanted by creating concentric capsulotomies in the anterior and posterior capsule, and capturing the edges in the groove. This effectively seals the capsule, giving any remaining lens epithelial cells nowhere to go. Dr Tassignon says that her residents have little trouble implanting the lens and the posterior capsulotomy is often easier to create that the anterior. She continues to develop the lens, and is working with a model that would allow replacing the optic as needed while leaving the haptic in place.

But while the bag-in-lens is immune to PCO, it is subject to Soemmerring’s rings, Dr Werner reports. Six post-mortem eyes ranging from four to 39 months after surgery showed progressive Soemmerring’s build-up, though none obscured the central area delimited by the rhexis openings, she says.

Nonetheless, the complexity of the bag-in-lens, which requires creation of two precisely sized and aligned capsulotomies and risk of vitreous loss, along with the potential for Soemmerring’s ring formation are problematic, Dr Spalton says. “I think it is an interesting idea but this IOL is unlikely to gain widespread clinical acceptance.â€

The need for precision surgery

All the premium lenses extant and in development require precision surgery for proper function. Dr Piovella notes that a perfectly round and centred capsulotomy is essential for the dual-optic lens to move reliably, and this can best be achieved with femtosecond lasers. “This lens and the laser were made for each other,†he says.

[caption id='attachment_1942' align='alignright' width='400' caption='The Miyake-Apple posterior view photo from the rabbit eye was taken five weeks postoperatively'][/caption]

The same might be said for multifocal lenses, which are highly sensitive to decentration and tilt, though the theoretical benefits have yet to be demonstrated, Dr Spalton says.

And no matter how precise biometry and incisions become, the healing process remains somewhat unpredictable, and refractive outcomes with it. Residual refractive error can be addressed with corneal surgery after lens implants, but new technology may make it easier to change the refractive properties of the implants, says Prof Artal.

Prof Artal is working with Calhoun Vision’s Light Adjustable Lenses not only to correct residual spherical and astigmatic refractive errors, but also to correct higher order aberrations and alter lens asphericity to enhance near vision. The lens is made of a photo reactive material that allows the shape to be adjusted in situ with a special ultraviolet lamp. When the final desired refraction and asphericity is achieved, it is locked in place with ultraviolet light.

By correcting the dominant eye for distance and neutral spherical aberration and the non-dominant eye for mild myopia with negative spherical aberration, J2 near vision and 20/20 far vision with excellent intermediate vision can be achieved. The negative spherical aberration reduces contrast sensitivity and distance vision slightly, but glare and haloes are less than with multifocal lenses, Prof Artal says. The lens adjustments are typically made within a couple of weeks after surgery, allowing for capsular contraction and corneal recovery. The process allows customising the amount of defocus and spherical aberration to patient tolerances and preferences.

“It is like a marriage. The effect of spherical aberration is always in combination with defocus and you always need to look at the two parameters together.â€

The process is precise to within 0.03 microns and 0.25 D. The biggest drawback may be that patients must wear eye protection to prevent sunlight from changing the lens shape until it is locked in, he added.

Femtosecond lasers may also one day be capable of adjusting any type of acrylic lens. A process known as refractive index shaping combined with a diffractive technique known as phase wrapping allows up to 5.0 D of power change in a 50 micron thick lens layer, according to Josef F Bille PhD of Heidelberg University, Germany, who is developing the technology for Aaren Scientific.

In theory, these customising technologies could be combined in the future with accommodative or PCO-proof designs to allow any type of lens to be customised in situ, Prof Artal says. Diffractive patterns to provide multifocality could be added or subtracted. With adaptive optics technologies to simulate vision, the combination of features could be precisely tuned to patient needs and comfort.

“It’s always about what is best for the patient. The customisable intraocular lens is the future,†Prof Artal believes.