Executive Summary – David J. Apple, MD

We address two questions regarding the complication of ‘glistenings’ in the Alcon Laboratories’ AcrySof IOL:

In Part 1, we estimate the incidence and accuracy of diagnosis of ‘glistenings’. Are they a common clinical problem that is often under-diagnosed; are they clinically significant to an extent that they sometimes may require explantation? Or, should we regard these as clinically unimportant medical curiosities?

Secondly, in Part 2, we focus our investigation on whether the ‘glistenings’, if and when they occur, sometimes cause visual problems that are clinically significant.

Part 1. Incidence and Accuracy of Diagnosis
We possess a unique database of 19,400 explanted IOLs collected in our laboratory. Of these 120 are explanted AcrySof IOLs that we accessioned over the 10 year period between 1996 and 2006 (almost the entire lifespan of the lens). We examined one hundred (100) of these and determined the actual number of IOLs with ‘glistenings’, the accuracy of the clinical diagnoses in each case and estimated the density (and hence the severity). Twenty lenses were excluded from the study due to different reasons.

The photomicroscopic analysis revealed ‘glistenings’ in 43 (43%) of the 100 lenses. Of the 43 lenses in which ‘glistenings’ were identified, only 6 had been noted clinically.

The ‘glistenings’ were mild in 14, moderate in 17 and marked in 12 of the 43 correctly diagnosed ‘glistenings’ cases.

These observations confirmed our and other’s previous findings that these entities are often overlooked and under-diagnosed. There was a vast discrepancy between the number of clinically-observed (6) and actual number (43) of observed ‘glistenings’ cases! This helps explain why there is so much controversy regarding their incidence.

There are three reasons that this entity is often under-diagnosed:

1. Not aware
2. Exam at wrong time
3. Disconnect

1. Many health care providers are simply not aware of this entity. We have noted that throughout the years between 1994 and 2006. Many ophthalmologists who had consulted with us were not familiar with this condition, particularly those who do not specialized in primary cataract surgery. A major factor for this is that there is no mention or description of ‘glistenings’ in the manufacturer’s literature or on the manufacturer’s package insert with the IOL.

2. A second reason that ‘glistenings’ are underdiagnosed and are therefore considered by some to be unusual is that many implantations are actually performed by active, high volume cataract surgeons who ironically rarely see this condition. This is because many of these surgeons do not examine implanted patients’ eyes at a post-implantation time that yields a high positive result for ‘glistenings’. A perusal of the cases studied in this report and also the cases studied both pre-2005 and post-2005 in Part 2 reveal that, in general, patient long-term follow-up patterns after AcrySof IOL insertion by the implantation surgeon are such they do not do follow-up exams at the correct time to yield the true numbers of ‘glistenings’. Other ophthalmologists or optometrists, who specialize less in primary implant surgery and are often more involved in general ophthalmology or refractive work, tend to see more patients long-term and to recognize these more. Ones’ perception regarding the incidence of ‘glistenings’ therefore may be skewed and may vary according to the type of practice one has. For example a common post-implantation regime for the typical high volume cataract surgeon – indeed the vocal opinion leaders - is as follows:

3. A third reason that ‘glistenings’ are often overlooked and have been underdiagnosed relates to the disconnect that often occurs between the patients’ signs and symptoms and the measured clinical tests such as the Snellen visual acuity and contrast sensitivity. We have found that most patients with ‘glistenings’, even those with moderate to marked ‘glistenings’ often retain a Snellen visual acuity which is deceptively good, ie. 20/20 – 20/40, often with few changes in contrast sensitivity (see part 2).

In other words, we are now finding that patients may have severe complaints while at the same time the measured values are relatively unaffected. This disconnect therefore can lead to confusion in the diagnosis. Patients whose ‘glistenings’ are associated with these almost normal measured values were generally considered “good enough” for the pre-2005 or pre-premium era. Patients could be and were discharged and informed that their post-operative results were normal or almost normal—as good as could be expected. This ‘disconnect factor’ has logically been partially responsible for ‘glistenings’ to be lost to the ophthalmologist’s ‘radar screen’, at least until recently.

1.) The manufacturer and the FDA have not provided sufficient information concerning ‘glistenings’ or a mention or warning of these on the package insert.
2.) There is marked variation in post-operative follow-up times among different authors so many may have been missed.
3.) And last but not least, there is often a large disconnect between patients’ clinical signs and symptoms versus the measured Snellen visual acuity and contrast sensitivity values, which makes it very difficult to compare each author’s data in order to achieve an accurate computation.

To summarize, this report is useful not only in providing a new incidence value of ‘glistenings’, but also, more importantly confirms the hypothesis, by us and others, that this condition is underdiagnosed.

Part 2. A Comparison of Fifteen Explanted Post-2005 Lenses with ‘Glistenings’. Are the Visual and Functional Alterations were Significant Enough to Warrant Secondary Intervention, Including Explantation?

In Part 2 we obtain information regarding the difference in the pattern of severity of ‘glistenings’ from the launch of the lens in 1994 to 2005 ( termed pre-2005) and 2005 to the present (termed post-2005). We also assessed their clinical significance. AcrySof IOLs evaluated in our database were grouped into two time periods according to the time of implantation:

Pre-2005 era: This covers the 10 year period from the time of launch of the AcrySof IOL in 1995 until 2005. This era is characterized by implantation of monofocal IOLs largely used in standard cataract operations. Fifty (50) patients implanted with AcrySof IOLs who subsequently developed ‘glistenings’ were referred to us in consultation.

Post-2005 era: The period ca. 2005 and onwards is the period of transition towards greater use of “specialized” foldable lenses, various refractive designs, including “premium” designs.

Also, fifteen (15) explanted AcrySof IOLs were studied. 10 were monofocal, 1 was a toric lens and 4 were the ReSTOR multifocal.

In the pre-2005 era the degree of visual degradation was such that removal/exchange was rarely performed. A very different pattern emerged with the 15 lenses inspected post-2005.

In all of the post-2005 cases the patients had symptoms that prompted them to request that the implanted AcrySof IOL be explanted/exchanged. Explantation was done in 14 cases. In one case the surgeon was concerned further about surgical morbidity in an already compromised eye so explantation was not recommended.

Results and Discussion:

Preliminary clinical observations by us and others as well as our clinicopathologic correlations lead us to consider that these lesions are much more common that has been believed by many., Also, they do indeed cause clinically relevant visual problems and that they may even interfere with the purported functions of the lens. In this case study we have found that even though the Snellen visual acuity has not been adversely affected, (most cases = 20/20 or better), post-operative visual dysfunctions or aberrations hindered the lens’ ability to provide the expected results. Furthermore, we noted in the single piece Restor multi-focal IOL the AcrySof SN60D3 design that the overlay of ‘glistenings’ may actually have precluded the lens providing the expected ‘premium’ result, namely multifocality.

‘Glistenings’ of the AcrySof IOL is one of a number of complications of the various modern Specialized IOLs) that we are now evaluating. There has been disagreement and debate among physicians as to diagnosis and management of ‘glistenings’. Some colleagues have written that ‘glistenings’ formation after implantation of an AcrySof IOL is a very rare occurrence that is clinically irrelevant, not requiring special attention, including subsequent explantation.

However, there are others who believe that it has actually been under-diagnosed. In Part 1 we provided evidence that ‘glistenings’ have actually often been under-diagnosed.

Pre-2005 was the period in which the expectations of surgeons, as well as the FDA and other overseers were modest in terms of what constituted a good visual result after standard cataract surgery. Expectations of the time were such that 98% of patients would be expected to achieve a Snellen acuity in the range of 20/20 to 20/40.

With respect to ‘glistenings’, the Snellen visual acuity in most patients with ‘glistenings’ ranged from 20/20 to 20/40. Even when patients returned to the doctor with complaints, in most cases they were informed that the results they received were the best quality vision possible for that era. Overall expectations for results were therefore relatively modest compared to today. In other words, in most cases of ‘glistenings’ researchers and surgeons concluded that any additional visual decrease that may have been caused, for example, by light scatter occurring in IOLs with ‘glistenings’, was more acceptable than the potential danger of an explant/exchange procedure. Most patients were asked to cope with any visual loss or discomfort that occurred. This was probably possible in part because of the mechanism of neuroadaptation. They were therefore advised to avoid the risk of surgical morbidity.

In sharp contrast this post-2005 era is the period that is now fast becoming associated with “premium” IOLs, “premium” surgery and hence “premium” results. Many patients of surgeons who have made the transition to the “premium channel” typically have much higher expectations for overall success and good visual restoration. Their surgeons now often promise a better chance for excellent results equivalent to the range of approximately 98% of patients achieving 20/20 or even better with few or no aberrations as opposed to the earlier mantra of 98% of patients achieving 20/40 or better. An opportunity to achieve a sterling result may be provided to patients who choose premium lenses. These patients are also often asked to pay higher fees for such premium results. If the surgical result is even slightly less than expected, the patient may complain.

We believe that this post-2005 era, based on the results of the 15 cases documented here, is the approximate time that a paradigm shift in our concepts of diagnosis and treatment is occurring.

A totally new concept in diagnosis and treatment is warranted. The paradigm shift regarding lenses with ‘glistenings’ is as follows:

In 100% of cases in this series, each patient had high expectations and therefore desired, almost demanded, explantation/exchange, including one patient who desired it but feared to undergo another operative intervention, and did not receive secondary treatment. These patients had hopes that a replacement of the lens they believed or were told had been the cause of the ‘glistenings’ with another IOL would provide a chance to achieve the hoped for premium results.

We noted 4 events that may occur with ‘glistenings’, including the following:

These studies and results are critical because infants, children, and young adults are now receiving implants. The AcrySof design is now being implanted in 95% of pediatric cataract surgery cases.9-11 Also the AcrySof ReSTOR SN60D3 model is now being researched and advocated for implantation of a multifocal model in children. 12 The reason for preference of this lens in children is because it is thought to be because of ease of implantation, stability in the eye, and enhanced biocompatibility. The latter was thought to be responsible for lowered PCO rates.¹³

Comments and recommendations from part 1 and 2

To summarize 1) the manufacturer and the FDA have not provided sufficient information concerning them or a warning of these on the package insert.

2) There is marked variation in post-operative follow-up times among different authors.

3) And last but not least, there is often a large disconnect between patients’ clinical signs and symptoms versus the measured Snellen visual acuity and contrast sensitivity values, which makes it very difficult to compare each author’s data in order to achieve an accurate computation.

I believe that the manufacturers, in contact with the Food and Drug Administration (FDA) should include a mention and description of this complication on the package insert. The lens was briefly withdrawn from the market because of ‘glistenings’ almost immediately after launch following the presentation by Nichamin and Apple (1995). Since that time, there has, to our knowledge, been no further FDA input. We believe it is time that overseers should call attention to this entity. It will be useful to have surgeons who have had to explants any lenses with ‘glistenings’ to forward lenses for laboratory study to supplement the database we have at present.

Alternatively, Alcon is attempting to modify the lens in order to assure that it will not be associated with ‘glistenings’. I am aware that Alcon has been researching an alternative model, tentatively called the AcrySof-2, in overseas studies in order to meet this need, but it is not yet available in the United States.

There are some other alternatives for surgeons who wish to continue with the hydrophobic acrylic material as their IOL material of choice. To date the other hydrophobic acrylic posterior chamber IOL designs being marketed and/or tested for FDA approval in the United States are the Tecnis-1, Abbott Medical Optics, the enVista lens, Bausch & Lomb, the AF-1 design, Hoya, and the EC-3 model, Aaren Scientific, that has just been approved by the FDA. The Tecnis-1 model from Abbott Medical Optics, is the first of these to receive FDA approval. It has not been implicated as having ‘glistenings’, not in clinical observations, including FDA studies and not in invitro analyses in our laboratory. Therefore, the surgeon could transition to this design without sacrificing his/her desire to continue with this hydrophobic acrylic material if he or she were otherwise content with the other major features of the lens itself.

Although ‘glistenings’ may often seem to be very unusual when viewed in terms of their occurrence in an individual practice, especially when – as is almost always the case – long-term patient follow-up is limited. However, this condition may represent a long-term ocular public health problem when viewed on a worldwide perspective.

Worldwide marketing of the AcrySof IOL commenced in 1995. Since that time ca. 5 million of these have been implanted. However, based on data collected by Smith (AUSCRS, 2009), one may conclude the following: Realizing that the dense ‘glistenings’ comprise 1% of cases, and that these are the ones most likely to evolve to clinically significant problems, it follows that 500,000 clinically severe cases may ensue on a global basis. Furthermore, according to Smith’s calculations, when one adds cases with “marked scatter”, (11% of cases) that calculates to be 5,550,000 cases with marked scattered ‘glistenings’ have existed .

Based on approximately 17 years observation of this lens, since the time of its launching in 1995, we have come to the conclusion that the complication of ‘glistenings’ in the AcrySof material and platform may be much more of a significant problem than many have heretofore believed.

A major reason that complications of ‘glistenings’ are often overlooked is that the Snellen visual acuity and contrast sensitivity are often unaffected. The visual dysfunction that occurs is related other factors, eg. various aberrations and others, some still not yet identified.