INTRODUCTION

As Kelman said, many years ago, cataract surgery will not be perfect while the patient needs optical correction for far or near. Getting independence of glasses for far, is the goal of all surgery in healthy eyes and can be achieved in most cases thanks to biometric advances. There is no doubt that we consider this surgery to be refractive and achieving emmetropia is a challenge for the surgeon.

The arrival of the Multifocal Lenses (ML) and their subsequent development, made us conceive hopes that it would be "easy" to achieve Kelman's wishes.

However, for various reasons, not all patients can benefit from the implantation of a ML. These lenses are generally complex optics designed for normal eyes. Their popularization and refinement, as well as the recent arrival of toric ML, makes them more frequently indicated and, sometimes, also in patients with certain concomitant pathologies such as pseudo-exfoliation (PSX) which, due to its characteristics (poor dilation , zonular alteration, association with glaucoma or greater postoperative inflammation), are located in the so-called "gray zone": patients not excluded but with greater or lesser risks depending on the severity of the condition.

Therefore, in these patients we must perform a thorough study with three objectives:

• Assess whether the patient is a candidate to implant a ML (independently of the PSX)
• Analyze the degree of affectation of the characteristics of this pathology
• Assess the risk/benefit that the patient can obtain with the implantation of a ML

Only then are we in a position to advise the patient if it is convenient to implant a ML, the risks that it entails (that the patient must assume), and the type of lens.

It is important to keep in mind that, in this pathology, given the large number of variables and different degrees of severity that it presents, there is no bibliography in this regard, so we must decide individually.

MULTIFOCAL LENSES

Despite the advances in the design that have occurred in the ML and toric ML, they should not yet be implanted in all patients, even in healthy eyes, as they can produce undesirable effects that are difficult to solve. The most frequent possible visual complaints can be classified into two categories: 1) Decrease in VA and/or contrast sensitivity; 2) Pseudophakic dysphotopic phenomena: such as halos and glare (Figure 1).

They occur with greater or lesser intensity depending on the type of ML, although none is exempt from these effects and all of them produce a decrease in contrast sensitivity.

We know that they occur to a greater extent in patients with:

• Macular malfunction
• Diminished contrast sensitivity
• Pupils of extreme sizes
• Decentration
• Severe dry eye
• Irregular astigmatism or greater than 0.75 D that we cannot correct.

In these patients, even without concomitant pathology, it can be a failure to implant a ML.

Another very important factor is the psychological factor of the patient. Implanting these lenses requires a “long” doctor-patient conversation, where the doctor must be clear about the patient's visual needs according to his activities and he must fully understand the real expectations that the MLs offer and the possible complications mentioned above: especially nocturnal halos that will yield as neuroadaptation occurs, and the need to use a spectacle to read in low light situations. The latter is usually accepted without problems by patients. Only then can the patient be satisfied.

If the patient is a good candidate to implant a ML, we analyze the degree of severity of the pseudo-exfoliation and how it could influence the visual/functional results of this type of lens.

PSEUDO-EXFOLIATION

PSX is an age-related disease that is characterized by the production and progressive accumulation of extracellular fibrillar material1,2. It occurs not only in the lens, where it is easily visible and historically known, but also practically in all ocular tissues of the anterior segment3,4 and in different organs of the body5 (Figure 2). It is associated with the formation of cataracts, mainly of nuclear type.

Its frequency varies a lot between countries and even between regions of the same country. In our setting (Ourense, Galicia, Spain) we have a rate in patients who will undergo cataract surgery of 22% in people over 70 years of age and 32% in people over 80 years of age6. It is also the most important identifiable cause of glaucoma, being 25% of all open-angle glaucomas7.

Why is it controversial to implant a multifocal intraocular lens?

PSX causes anomalies in the eyeball that condition the use of Premium (multifocal) lenses, the most important ones that we are going to analyze are:

1 - Poor pupillary dilation:

It is due to the presence of PSX material in the stromal or muscular tissue and vascular anomalies that lead to hypoxia and degeneration of this tissue (Figure 3). It not only hinders surgery but can also condition the functional performance of these implants, in some cases for far vision and in others for the near vision depending on their design. Currently, we do not have any multifocal lens that is totally pupil-independent, although there are differences between them.

2 - Endothelial involvement:

Responsible for a possible corneal decompensation after surgery. Focal deposits of PSX material produced by endothelial cells appear on the posterior corneal surface and on Descemet’s membrane. It is called pseudo-exfoliative keratopathy8 (Fig. 4). It can really affect surgery more due to the decrease in cell density that is usually between 800-1500 cells/mm2. It is important to take it into account and explain it in the informed consent, especially if the anterior chamber is narrow.

3 - Association with glaucoma:

Approximately 25% of patients with PSX have an elevation of IOP and of these, 30% suffer from glaucoma9. In patients who are going to undergo cataract surgery, the frequency of glaucoma is 49% compared to 6.8% in those who do not have PSX9 (Figure 5). Glaucoma also presents differences with respect to chronic open-angle glaucoma such as:

• Higher IOP at the time of diagnosis10 and with greater possibilities of developing glaucoma11.
• Glaucomatous damage develops earlier and progresses more rapidly12.
• Alterations of the visual field are more advanced at the time of diagnosis14,13.
• Worse response to treatment.

In short, it is a more severe glaucoma.

Glaucoma patients have a decrease in contrast sensitivity, that we must assess preoperatively, because all the ML also produce it. We should not forget that contrast sensitivity has been shown to be a more sensitive measurement than visual acuity to assess the patient's ability to perform daily activities. It is therefore necessary to be rigorous in the assessment of the optic nerve and glaucoma, to know its degree of involvement, since it is a key point on which to accept or reject this patient (Figure 6).

4 - Increased postoperative inflammation:

PSX presents a chronic rupture of the blood-aqueous barrier that accompanies the ischemic changes that occur in the iris15. It is responsible for the greater inflammation that occurs in the early postoperative period.

In order not to increase inflammation, it is important to avoid any manipulation of the iris as much as possible. Anti-inflammatory treatment should be more aggressive than in a healthy eye.

The greater the inflammation, the greater the chances of a capsular contraction occurring that could lead to decentration of the lens. Likewise, patients with pseudo-exfoliation have a smaller rhexis size that causes greater fibrosis and as a consequence a greater tilting of the lens16. For this reason, it is important to assess the possible contraction after the first month and, if so, perform relaxing radial capsulotomies with the ND:Yag laser, releasing the traction that the capsule exerts on the zonule (Figure 7). The capsular contraction is greater in eyes with PSX and in zonular alterations. The presence of a ring minimizes the contraction although it can happen equally, but it facilitates to carry out a possible subsequent relocation if necessary.

5 - Progressive zonular weakness:

Possibly the most incompatible anomaly with the implantation of multifocal lenses, since although it is not revealed in the operation, its progressive nature can cause, years later, the dislocation of the IOL-bag complex (Figure 8).

It is true that the incidence is low although very difficult to know exactly. A study carried out in Sweden17, a country with a high PSX index, only 5 of 800 cataract patients required surgery for dislocation of the complex at 10 years. However, they do not indicate the proportion of patients with PSX among the operated patients. It would be very interesting to know this figure.

Without reaching these extremes of dislocation, a study by Ostern et al18 found that 6 years after an uncomplicated surgery, the IOL-capsular bag complex tends to decentralize vertically to a greater extent and in a significant way in pseudo-exfoliative patients than in the control group. This data is important because small deviations cause a significant decrease in the visual quality/function of these lenses, which must be perfectly centered in relation to the visual axis. This vertical progressive decentration is greater in patients with glaucoma. In the analysis performed 12 months after surgery, there were no significant differences. They were progressing with time.

The zonular affectation begins in the first stages of the disease where PSX material can already be observed, the fibers acquiring the typical appearance as if they were covered with frost19.

Fragmentation occurs at three levels20 (Figure 9):

1. A) At the area of ​​fiber insertion in the anterior capsule where the material produced in this area invades the zonular lamellae separating them from their insert;
2. B) At their origin, in the anchorage zone in the ciliary processes, by the same mechanism with PSX material produced by the cells of the non-pigmented ciliary epithelium;
3. C) In the zonular fiber itself, due to the action of lysosomal enzymes that cause their proteolytic degradation.

Assessing the zonular involvement previously is key in these patients. It is important to analyze both direct and indirect signs. Before dilating the pupil, we assess indirect signs such as phakodonesis or iridodonesis.

Sometimes to analyze these signs it is necessary to instill a drop of 2% pilocarpine to relax the zonula; in this way they are better appreciated. Also, paying attention to the depth of the anterior chamber, very deep or very narrow, are indirect signs of zonular alteration and to a greater extent if there is asymmetry between both eyes (Figure 10).

It is important to analyze indirect signs well, since in this way we can avoid the so-called "invisible" surprises that occur during surgery.

ALGORITHM OF ACTION

Once the severity of the condition is known we are in a position to assess the benefits/risks associated with the implantation of an ML in a patient.

Two different situations are posed:

1) Patient that requires refractive lensectomy and 2) patient with cataract.

• Refractive lensectomy: The visual demands are greater than in patients with cataracts since the visual quality with correction is more or less perfect. They are patients usually under 60-65 years of age where the pseudo-exfoliation is very mild or does not yet show signs. I would not implant a ML in three situations: 1) asymmetry in pseudo-exfoliation, the eye with greater or only signs of PSX will have a more rapid and aggressive progression than normal; 2) when the patient has glaucoma, although it is controlled with treatment, given the aggressiveness of PSX; 3) signs of advanced pseudo-exfoliation.

In the cases of patients with mild, bilateral PSX and good dilation, it would not be inconvenient to implant a ML.

• Patients with cataracts

Should be interested in ML and request it personally, although all patients should be informed that there is ML, but that perhaps in their case they are not the most appropriate. We always warn that it will be a complicated surgery and that if we observe any sign of zonular alteration, we will implant a monofocal lens.

We would not implant ML in any case if:

• Pseudo-exfoliative glaucoma exists with moderate affectation of the visual field although it is controlled with treatment.
• Advanced cataracts are present, since they are related to greater zonular alteration, although they are not the patients that usually demand them (Figure 11). A case to consider is when the nuclear cataract makes the eye myopic and the patient can read without glasses. I would be more in favor of implanting it in this patient since he is delighted with his near vision without glasses.

I would implant a ML to the patient who requests it with bilateral pseudo-exfoliation, good pupillary dilation, pupil in normal ranges and, of course, no signs of zonular alteration (Figure 12).

In a gray area, I would place the patient with glaucoma well controlled with a single active principle, with a slight but stable alteration of the visual field, and older than 70 years. Note that being "a little" more supportive when there is a mild glaucoma in patients with cataracts is due to, in addition to age, because the previous VA is bad due to the cataract and, therefore, they notice less decrease in contrast sensitivity.

The patient's age can be a factor that in cases of doubt tilts the balance in one way or another.

CONSIDERATIONS ABOUT THE SURGERY

• Assess that the depth of the anterior chamber, endothelial count and signs of zonular alteration are correct.
• Try not to use mechanical dilation and avoid manipulating the iris.
• Enter the phaco tip in the anterior chamber with very low irrigation and raise it until you find the right height (do not deepen the chamber and keep it stable).
• Vertical chop technique.
• Large capsulorrhexis (5.25-5.50 mm).
• Protect the endothelium with viscoelastic during the emulsification of quadrants.
• When exiting the anterior chamber with the phaco tip, fill it in previously from the paracentesis with viscoelastic to avoid collapses that can damage the zonule.
• Implant a capsular ring, in these cases we always do it as late as possible, before injecting the ML (Figure 13).
• Viscoelastic aspiration of both the anterior chamber and the capsular bag.
• If CCC is smaller than 5 mm, aspirate the epithelial cells of the anterior capsule in contact with the optics.
• Avoid tension peaks.
• More intense anti-inflammatory treatment needed.
• Monitor the potential capsular contraction after the first month.