Presbyopia / SPO - 3.2.6.5. Cystoid macular edema in multifocal lenses

3.2.6.5. Cystoid macular edema in multifocal lenses

Conceição Lobo

Centro de Responsabilidade Integrado de Oftalmologia - Centro Hospitalar e Universitário de Coimbra (CRIO-CHUC), Portugal

Faculdade de Medicina da Universidade de Coimbra (FMUC), Portugal

Associação para a Investigação Biomédica e Inovação em Luz e Imagem (AIBILI), Portugal

INTRODUCTION

Cataract extraction is one of the most commonly performed surgeries worldwide. There has been a remarkable evolution regarding the technique used, which together with phacoemulsification and implantation of a foldable intraocular lens (IOL), is considered today an extremely safe and efficient surgical procedure1,2.

The increase in life expectancy, as well as the constant technical evolution, namely the higher precision, innovations in instrumentation, and the evolution in IOL design itself, have contributed to making this a very common procedure with excellent visual results, that allows patients to get better eyesight earlier and earlier1-4.

In addition, with the appearance of multifocal IOLs (MIOLs), the use of cataract surgery and concomitant correction of presbyopia is now being viewed as a possibility. Thus, this type of IOLs can be used, not only in the context of the existence of cataract, but also in situations where the lens is to be removed and replaced by an IOL to correct a refractive error, and/or the loss of accommodation. In the latter case, the procedure fits into the so-called refractive lens surgery. That is, refractive lens surgery is essentially the same as cataract surgery. However, in this case the procedure is performed primarily to change the refractive properties of the eye and not to remove a cataract that has developed.

Thus, both in modern cataract surgery and in refractive lens surgery, one should expect not only improved vision but also independence from glasses. This last aspect has become increasingly important, requiring surgeons to be more concerned with minimizing postoperative refractive error, something that obviously becomes even more relevant in refractive lens surgery.

Given therefore that with the increasing technical evolution there has been a convergence between cataract treatment and correction of the patient's refractive error, cataract/refractive surgeons have been in recent decades proposing this type of surgery ever earlier.

Even in uneventful surgery however, complications such as cystoid macular edema (CME) may develop, that may result in a suboptimal visual postoperative period2,5–7. Although the pathogenesis of CME is not completely known and there are different risk factors that may contribute to its development, the contribution of postoperative inflammation is generally accepted8. Given therefore that treatment options depend on the underlying cause, the usual therapeutic approach for CME prophylaxis and treatment is to block inflammatory mediators. Consequently, anti-inflammatory drugs, including steroids (SAIDs) and non-steroids (NSAIDs), have been postulated to play a role in both prophylaxis and treatment of CME.

However, the lack of a uniformly accepted definition of CME, the controversial data on some risk factors and until very recently the paucity of randomized statistically significant studies, have made use of anti-inflammatory drugs, especially in prevention of the CME, a controversial subject.

In this context, we intend to address essentially two relevant topics. First, the need for more careful patient selection, including a more detailed preoperative study, in view of the possibility of performing a cataract/lens surgery with multifocal IOL implantation. Second, we will establish which is the better prophylactic and therapeutic regimen for pseudo-phakic macular edema. The later will be based on existing studies, including the multicenter study promoted by the European Society of Cataract and Refractive Surgeons (ESCRS) – PREvention of Macular EDema after cataract surgery (PREMED) study, whose results were recently disclosed.

PSEUDOPHAKIC CYSTOID MACULAR EDEMA

CME after cataract surgery, or pseudophakic (PCME), was initially reported by Irvine in 1953 and demonstrated angiographically by Gass and Norton in 1966, then designated as Irvine-Gass Syndrome9-11.

Angiographic CME is diagnosed in patients who are asymptomatic as far as visual acuity (VA) is concerned, but have instead fluorescein (FA) effusion detected from the peripheral capillaries. The clinical CME is diagnosed when a patient presents with a decrease in VA and presents compatible alterations in FA and/or fundoscopy12,13.

Currently however, clinical diagnosis is usually confirmed using only optical coherence tomography (OCT)14-16.

INCIDENCE

This is the most common complication of cataract surgery but given the great heterogeneity of definitions and diagnostic criteria, its incidence is difficult to define, with reports ranging from 1% to 30%. This variability is related not only to the diagnostic criteria used, but also the different surgical techniques, with both isolated and Femtosecond laser assisted phacoemulsification associated with lower incidences17–20. Thus, when considering clinically significant CME in patients without risk factors, the incidence is only 1-2%, whereas when considering CME defined by the OCT, and particularly by the FA, this incidence is significantly higher21-26. The great variability of incidence rates presented in the literature is also due to the fact that in many studies the patients are already under the effect of some specific anti-inflammatory, either before or after surgery27-29. In addition, the heterogeneity of patient populations that are evaluated, with different risk factors, also contributes to the difficulty in determining the actual real incidence of PCME. It is therefore of paramount importance to recognize the many variables involved, and to take into account their possible impact, when interpreting the results of clinical trials evaluating potential treatments for PCME. Especially since despite the supposed low incidence of this complication, given the number of cataract surgeries performed annually, this issue is still a topic of particular relevance.

ETIOLOGY AND RISK FACTORS

PCME may occur after uncomplicated surgery in healthy patients, after complicated surgery, or after surgery in patients with other ocular conditions such as uveitis or diabetic retinopathy.

The specific etiology of CME is not fully understood. It is recognized that other factors such as the type of surgical technique, vitreous-macular traction and surgical complications, such as loss of vitreous and the integrity of the posterior capsule, are possible triggers5,30,31.

Regarding the surgical technique, its role is clear, given that with the evolution of the technique from intra- and extracapsular to phacoemulsification through small incision, there was a clear decrease in the incidence of this complication31-33. This is explained by the minor damage of the blood-water barrier (BWB) following phacoemulsification with an intact continuous curvilinear capsulorhexis, compared to previous traumatic and invasive techniques5,31,34-36.

The role of vitreous-macular traction in the development of PCME is explained by the fact that the vitreous, in the foveal area, is inserted in the internal limiting membrane, which is attached to the Müller Fibers, so that the tensile forces exerted in this area can affect these cells, leading to the appearance of edema9,18,37,38. In addition, the minimal traction in the vitreomacular interface that occurs in phacoemulsification, compared to previous techniques, would also explain this reduced risk8,33,39.

Although PCME can occur after surgery without complications, different studies confirm that certain surgical complications increase its risk. Thus, either posterior capsule rupture, loss of vitreous, or even secondary capsulotomy (including YAG laser capsulotomy) are associated with a higher rate of CME5,13,40-43. The vitreous incarceration and prolapse of the iris further worsen the visual prognosis44,45. Retention of crystalline fragments, even when removed by pars plana vitrectomy, is another complication associated with an increased rate of CME and more severe visual loss46-49.

Thus, the incidence of CME in complicated surgeries with falling crystalline fragments in the vitreous is actually higher, not only because the retained crystalline fragments themselves cause usually more severe inflammation, but also because we are facing longer surgeries, that may often require a second intervention50,51.

The existence of other associated pathologies, such as diabetes, with or without retinopathy, and uveitis, also pose an increased risk for the development of CME52-54.

In diabetic patients not only is the possibility of worse VA greater, but also the two clinical forms (diabetic macular edema and Irvine-Gass syndrome macular edema) can probably coexist55–57. In the preoperative evaluation, it is very important to consider that if the patient already has macular edema, it should be treated before cataract surgery, or when this is not possible, the use of an intravitreal anti-inflammatory should be considered at the time of surgery.

Similarly, in patients with a history of uveitis, with an increased risk of developing CME, appropriate preoperative assessment should be made, taking into account the type, cause and current status of the disease, in particular by adapting therapy accordingly58-60. Thus, in these patients, it is especially imperative to control preoperative inflammation and to introduce postoperative medication according to the expected risk.

PATHOGENESIS

Although the pathogenesis of CME after cataract surgery has already been described for many years, some aspects remain uncertain. However, clinical observations and experimental studies indicate that it is indeed multifactorial45,51.

Prostaglandin-mediated inflammation and subsequent alteration of BWB and the Blood-Retina Barrier (BRB) are probably the most important factors involved35,61-65. Regarding the role of inflammatory mediators, it has been postulated that after cataract surgery, some mediators such as prostaglandins, cytokines and other vascular permeability factors are released from the anterior segment of the eye and diffused into the vitreous and retinal cavity, stimulating rupture of the BRB31,36,65-68, with subsequent outflow of fluid through the retinal vessel endothelium wall and retinal pigment epithelium (RPE) in the perifoveal area, resulting in macular edema31,45,65,69.

There are several studies supporting the idea that the arachidonic acid cascade is not the only chemical mediator related to postoperative inflammation. It is believed that other substances are also involved, such as complement70, platelet activation factors (PAF)71, cytokines72, nitric oxide74 and endothelin73,75. A well-studied cytokine is interleukin-6 (IL-6)72. An increased level of this mediator was found in the aqueous humor of patients undergoing cataract surgery22,72.

Our improved knowledge of cyclooxygenase (COX) has allowed for a better understanding of the different pathways involved, with some studies confirming that there are two types of COX76,77. A constitutive isoform, COX-1, which is responsible for the physiological biosynthesis of prostaglandins, associated with normal tissue homeostasis and present in all tissues. COX-2, the induced isoform, which biosynthesizes prostaglandins, is associated with inflammation and appears in response to stimulation of proliferative factors, such as IL-1B or endotoxin78.

It is known that during cataract surgery, associated with surgical manipulation, a variable degree of trauma can occur in the iris, which, being a metabolically active tissue, releases inflammatory mediators. After surgery, a physiological resolution process occurs, which, although slow, progressively suppresses inflammation79. For this reason, in about 90% of patients with macular edema after cataract surgery, spontaneous resolution of edema and VA recovery occurs. It will be specifically in situations where the leakage from the perifoveal vessels is more excessive, that the resolution is more complicated, leading to an irreversible impairment of VA18.

DIAGNOSIS

The signs and symptoms of clinically significant CME usually develop 4 to 12 weeks after surgery, peaking between 4 and 6 weeks. Usually the patient complains of a deterioration of VA, after an initial period of improvement due to cataract removal80,81.

The diagnosis of CME can usually be made in the clinical examination, with evidence in the observation of the ocular fundus of perifoveal cystic spaces, traditionally confirmed with FA, to document the classic petaloid pattern of perifoveal effusion12,13 (Figure 1).

Figure 1: FA image showing the classic petaloid pattern of perifoveal effusion in PCME.

Currently, the most objective evidence is obtained with OCT, since it is a non-invasive method, and documents not only the pattern of edema, clearly showing the cystic spaces (Figure 2), but also quantifies the increase in retinal thickness facilitating the follow-up of the evolution of edema14.

Figure 2: OCT images showing the typical cystic spaces of PCME.

Additionally, it is recognized that there is a better correlation between the increase in thickness measured by the OCT and VA, than with the changes in the FA, so that the OCT is effectively the exam of choice, not only for diagnosis in daily clinical practice, but also for patient follow-up15,16.

When facing a clinical CME, the initial approach is made with the introduction of topical SAIDs, and there is usually a good response. Some cases may respond poorly to this conservative treatment and persist for more than six months, giving rise to the concept of chronic CME. In these cases, the associated loss of vision proves to be a worrying complication.

MULTIFOCAL IOL

Although multifocal IOLs (MIOLs) have been on the market for several years, it has been especially in recent years that their use in cataract surgery has been steadily increasing. This is due to the continual improvement in performance, which has evolved from refractive/diffractive to currently also trifocal and accommodative, but also because more and more patients are seeking independence from glasses. Thus, this type of IOLs can be used, not only in the context of cataract, but also in situations where the intent is to remove the lens and replace with an IOL to correct a refractive error, and/or loss of accommodation, i.e. in refractive lens surgery.

For success to be achieved in these cases, the selection of the candidate for this type of IOL will have to be more judicious. The first step will be to understand if the patient is motivated by independence from glasses, acknowledging however the limitations inherent to this type of IOLs, and having as such realistic expectations82.

The second step is to determine possible ocular comorbidities. Generally, in MIOLs the available light is divided between the foci for far and near. For this reason, all situations that affect VA or the quality of vision are a relative or absolute contraindication for this type of IOLs, such as amblyopia, corneal pathology (such as keratoconus, leukomas or Fuchs’ endothelial dystrophy), maculopathy (such as macular degeneration or diabetic retinopathy), glaucoma and uveitis82,83. Thus, a more extensive preoperative ophthalmologic evaluation is required, including corneal topography, endothelial cell count, and preferably OCT. The adequate calculation of IOL to implant is another aspect of capital importance for the success of this type of surgery.

From all of the above, it is assumed that in the specific case of planning the implantation of a MIOL, the patients considered to be at risk of developing CME are already contraindicated, namely, diabetics and uveitis patients. However, as is well known, even in patients without other eye conditions and even in uneventful surgery, the possibility of developing CME still exists. For this reason, both prophylactic and therapeutic measures for CME will be the same whether these are monofocal or multifocal IOL patients.

Another aspect to consider will be whether this type of IOL is associated with an increased risk of developing CME. Although there are few studies on this topic, all point to a low incidence and overlap with that reported for monofocal IOLs, i.e. 0.12-2%84-86. In these studies, the same limitations are mentioned, such as populations with different risks, use of different methods of diagnosis and criteria of evaluation of CME, as well as different prophylactic schemes before and after surgery. In addition, existing studies comparing different MIOLs with respect to the development of CME, also show no statistically significant differences with respect to their incidence86.

Thus, the scope of this chapter is not to speak specifically about MIOLs, but rather to warn of the need not to devalue the possibility that, even in patients where it is implanted, this complication – PCME, may still occur.

In this context, general prophylactic and therapeutic measures in PCME will be addressed, based on current knowledge.

GENERAL STRATEGIES

Angiographic CME is not necessarily associated with changes in VA, it is generally asymptomatic, and there is a spontaneous resolution in most cases. However, in about 1-3% of cases, this may not happen, with angiographic changes persisting, corresponding to the so-called clinical CME, with a continuous decrease in VA81,87.

Additionally, even clinical CME is in the vast majority of cases a self-limiting disorder. However, in a small percentage of cases, which, given the number of surgeries performed each year, may account for a significant number of patients, this may not happen and may result in long-term visual deterioration, which is often difficult to treat. It is important therefore, to reflect on existing studies on CME prevention and treatment measures, as well as on the recommendations of major ophthalmic societies25,81,88. How to deal with PCME is a topic that should concern all cataract and refractive surgeons, since as mentioned initially, the expected goal of this surgery is vision excellence, especially when done with refractive purpose, and even more so than a simple cataract case that has developed and needs to be removed.

For several years, numerous studies have been published, with varying degrees of clinical evidence, pointing to the fact that the use of SAIDs is useful, not only in the treatment of PCME, but also in its prophylaxis, so their use is an almost universally accepted practice87,89,90. However, as already mentioned, the target populations in these studies were not always the same, especially in relation to risk factors, and diagnostic methods were not always standardized81,88. In addition, in many studies there is a comparison of populations already doing different pre- and post-operative regimens. That is, the statistical significance of many of these studies was doubtful, so that there was always some level of controversy91,92. There was, therefore, the urgent need to develop a large randomized, well-designed study that would effectively clarify the best therapeutic regimen, namely in the prophylaxis of PCME25,91. The PREMED study aimed precisely to provide guidelines based on clinical evidence to prevent PCME in diabetic and non-diabetic patients, thus filling this gap. Within this chapter, the most relevant results of this study will be presented, relative to non-diabetic patients only.

In context, it is important to emphasize that the therapeutic approaches available for the prophylaxis and treatment of PCME have always been based on theories based on its pathogenesis55,90. That is, based on the different inflammatory mediators, mainly prostaglandins, the approach to PCME has always focused on the development of drugs to block these mediators and, if possible, with minor side effects, specifically NSAIDs and SAIDs93. NSAIDs are non-selective, inhibiting either COX-1 or COX-277,94,95, while SAIDs interfere with phospholipase A2 activity by selectively inhibiting COX-296,97 (Figure 3).

Figure 3 – Arachidonic acid cascade and mechanism of action of IEAs and NSAIDs

The SAIDs are effective and have always been considered as the reference for the treatment of ocular inflammation but are presumably associated with an increased incidence of adverse events, including increased intraocular pressure (IOP), in a small percentage of patients98.

Because of this limitation, there has always been research being developed to find alternative therapies with similar efficacy but with fewer adverse effects, notably NSAIDs. Additionally, these NSAIDs have the advantage over SAIDs of contributing to the control of pain and discomfort during surgery99,100.

The different available NSAIDs present variable potencies against COX-1 and COX-2 in cataract surgery. The specificity against COX-2 activity is important because it is the isoform of the enzyme that is considered to be the main mediator of ocular inflammation27,87,90,101-104. There are several EU-approved NSAIDs for the treatment of postoperative inflammation of cataract surgery: ketorolac, diclofenac, flurbiprofen, indomethacin, nepafenac and bromfenac104.

The two most recently introduced NSAIDs on the European market – nepafenac and bromfenac – have some potential advantages, due to their faster penetration into ocular tissues, given their greater permeability through the cornea90,99,100,105-111.

Clinical evidence also suggests that the combined use of SAIDs and NSAIDs is synergistic, based on the different mechanisms of action of the two drugs101-103,112-115.

Another point of discussion is related to the timing of initiation of SAIDs and NSAIDs prior to surgery12. There are several studies that point to the benefit of initiating NSAIDs prior to surgery, and in the recovery of VA in the immediate postoperative period116. In addition, their use is also recommended for the prevention of intraoperative miosis17-119.

PROFILAXIS OF PCME

As already mentioned, a correct pre-operative assessment of patients, separating them into "normal" vs. "risk" patients, and defining a personalized treatment with a therapeutic regimen adapted to each situation, is fundamental. This way, if any risk situation is identified, attempts can be made to improve or correct it, as these patients are supposedly not indicated for MIOL implantation.

How to proceed with patients at risk, especially diabetics, with uveitis and macular pathologies, will not be addressed in this chapter, instead only what to do with these "normal" patients will be discussed.

The PREMED study reinforced the need for pre-surgical prophylaxis with topical NSAIDs or SAIDs even in these patients, at least 2 days before surgery, and to maintain them until at least 4 weeks after surgery. It has been shown that, using only NSAIDs is superior to using only SAIDs, in the prevention of PCME. However, the group where NSAIDs were combined with SAIDs showed even higher preventive efficacy, exhibiting an even lower incidence of PCME, so the idea of a synergistic mechanism of action was confirmed. In this study, bromfenac 0.09% 2 times/day was used as NSAID and 0.1% dexamethasone 4 times/day as SAIS, with a reduction of 1 drop/week after the first week.

It should be noted that with regard to the use of topical NSAIDs as prophylactic, there were already several published studies with high degree of evidence, including literature reviews and meta-analysis showing the benefit in PCME, not just clinical, as based on OCT27,120-124.

In the postoperative period of any patient, even when the surgery has been uneventful, it is always necessary to remain vigilant. If in the immediate postoperative period excessive inflammation is noticed, it will be necessary to change or modify the type of prophylaxis. That is, the prevention of inflammation is very important, even considered to be the key factor. This means that despite the careful selection in the preoperative period, a patient may still appear with more inflammation, so we should increase the dose of SAIDs and, if necessary, watch it even more closely. If this medication adjustment is not enough, it may be that the patient is developing PCME, and if that happens, then treatment is given to that effect.

Another possible option includes complications during surgery. That is, even in a patient who was not anticipated, complications may still occur intraoperatively. Although in theory the ideal is to avoid complications, they can occur and will have to be resolved if possible, in the same surgical act. On the other hand, in these cases, even if it was planned, the placement of a MIOL is contraindicated. Once again, this patient becomes part of an increased risk group for the development of PCME, so the medication will have to be adapted immediately and closer surveillance instituted. If indeed PCME develops, then it will also be treated accordingly.

TREATMENT OF PCME

Despite efforts to introduce preoperative therapy, care during surgery, and postoperative control, there are situations in which the patient usually has a low VA between the 4th and 6th weeks, with macular edema as the main cause. All of this applies to patients with either monofocal or multifocal IOLs, and the evidence points to the importance of having a PCME algorithm type scheme instituted. Situations in which hypothetically postoperative medication has already been discontinued will be considered here.

Thus, the first step will be the reintroduction of steroid and non-steroid topical therapy, aiming at improving VA103,122,125. This measure is based on existing systematic reviews, which refer to some randomized studies reporting the positive effect on PCME126. NSAIDs should be reintroduced at a dose according to the selected anti-inflammatory and SAIDs at least 4 times/day. This treatment will be continued for about one month and the patient will be observed again at the end of this period. If the VA has improved and the OCT confirms it, the medication is being effective and should be continued for at least another 2 months. If there is no improvement at the end of this month there are some alternatives. There are several studies, again with a greater or lesser degree of scientific evidence, in favor of one or another scheme.

Based on studies with the most scientific evidence, as well as literature reviews and meta-analysis, the most recommended options will be presented. Acetazolamide 500mg per day may be used initially for about one month80,127-129. Alternatively, the subconjunctival/sub-Tenon’s injection of triamcinolone can be used at a dosage of 40mg. The use of periocular corticosteroids, when there is failure of topical treatment, has shown to have a beneficial effect130. Thus, if the patient responds well it is possible to administer another 2 or 3 injections every 3 to 6 weeks. If the response is not positive, or the edema is initially excessive, or the patient presents with any other risk factor, it is possible to proceed immediately to the intravitreal injection of 4mg of triamcinolone131. This type of approach allows a greater concentration of medication at the macular level, which is the goal.

The rationale for the use of acetazolamide, which inhibits carbonic anhydrase, is based on its ability to induce acidification of the subretinal space, and as such, promote resorption of accumulated fluid in the retina to the choroid through RPE. That is because at this level the external BWB exists, with an active transport system, which when activated, allows draining of the excess fluid in the macular area, thus contributing to resolving of the macular edema80,128,129.

In the case of intravitreal injection several studies confirm the benefit of using triamcinolone130,132. The major limitation of this type of medication is often the need for repeated injections130,133. This could possibly be improved with controlled drug delivery systems. These devices are currently used with benefit and were approved by the FDA in 2009 in the case of branch venous occlusions and non-infectious posterior uveitis. They have also been approved for macular edema after uveitis and after cataract surgery in diabetic patients. The efficacy and safety of a dexamethasone implant for treating post-surgical CME, including Irvine-Gass Syndrome, was evaluated in a study called EPISODIC, with favorable results134,135. However, despite being used in diabetic patients and in cases refractory to other treatments130,133, given the possible side effects, this procedure should be avoided, especially in non-diabetic patients, with other alternatives being chosen.

Antiangiogenics, already used to control diabetic macular edema, are also proposed for PCME, regardless of whether or not the patient is diabetic. Cases that have not been resolved using another type of therapy are being considered here. VEGF is a potent inducer of BRB alteration occurring in the postoperative period of cataract surgery, so hypothetically antiangiogenics should contribute to the control of macular edema93. However, the studies have shown controversial results136. A meta-analysis even considers that existing studies on the use of bevacizumab have a low or very low level of evidence137. For these reasons, antiangiogenics, although effective in PCME, should be considered only as an alternative, in cases where other options do not work.

More recently, the possibility of using immunomodulatory therapy, namely the use of interferon and infliximab, has also emerged, and efficacy in resolving macular edema has already been demonstrated in some pilot studies128,138. Note that these are limiting, refractory situations where everything has been tried.

Ultimately, surgery can always be considered to treat these situations. This procedure should also be performed when there are complications in cataract surgery, namely, the IOL is misplaced, the pupil is pulled, the vitreous is incarcerated, among others. In these situations, surgery is inevitable and should be the first step. Even if the surgery has not been complicated, if the patient has already tried all possible therapies with no response, a vitrectomy may be considered. The rationale for the later is to try to release and remove any possible vitreous adhesions, in order to reduce inflammatory mediators139,140. This procedure may also make sense as an attempt to improve access to the posterior pole for the topical therapies being used.

CONCLUSIONS

Foldable IOL implant phacoemulsification is one of the most commonly performed surgeries. The procedure is efficient, and an uneventful surgery is generally associated with good visual outcomes.

With the advent of MIOLs and their improved performance, their use not only in cataract surgery, but also in refractive lens surgery, has become an option to consider. However, regardless of the type of monofocal or multifocal IOL, PCME can develop and may result in suboptimal postoperative vision, and although the incidence of this complication is low, given the number of surgeries performed annually throughout the world, it persists to be a major problem.

The most widely accepted explanation for the pathogenesis of PCME is anterior segment inflammation associated with BWB rupture, with consequent release of inflammatory mediators, particularly prostaglandins, which diffuse to the posterior pole, leading to subsequent rupture of BRB and development of macular edema.

Although FA has been considered indispensable for the diagnosis of PCME, OCT is now the method of choice because it is non-invasive and has other advantages such as objectively measuring retinal thickness, which is the parameter that best correlates with the VA.

PCME prophylaxis and treatment guidelines, which apply regardless of IOL type, have always been based on the premise that prevention of inflammation should be the primary goal.

Thus, careful selection of patients, with a correct preoperative evaluation, allows them to be classified as "normal" or "at risk", and this is a fundamental step. When identifying patients with risk factors, we must correct or improve these if possible, and adapt the treatment regimen accordingly. This step also allows you to select or reject a patient as a candidate for a MIOL.

The usual therapeutic approach for both prophylaxis and treatment, which applies regardless of the type of IOL, is aimed at blocking inflammatory mediators using topical NSAIDs and SAIDs. The PREMED study reinforced the benefit of the combined use of NSAIDs and SAIDs in the prevention of PCME.

Most studies provide clinical evidence that the use of preoperative SAIDs reduces the incidence of PCME and improves short-term VA, although it is unclear whether this strategy also affects long-term outcomes.

Despite the measures taken to prevent PCME, this can still occur and so therapeutic measures have to be implemented. These again go through the use of topical NSAIDs and SAIDs, which in most situations allow their resolution. In some cases, additional medical measures may be necessary, such as the use of SAIDs (sub-Tenon, subconjunctival or intravitreal) or intravitreal anti-VEGF, or surgery such as vitrectomy in borderline situations.

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