Source: Healio Interviews
Disclosures: Devgan reports no relevant financial disclosures. Do reports she is a consultant for Boehringer Ingelheim, Genentech, Kodiak, Regenxbio and Santen. Hovanesian reports he is a consultant for Alcon, Bausch + Lomb, Johnson & Johnson and Carl Zeiss Meditec. Kuppermann reports he is a consultant for Allegro Ophthalmics, Allergan, Aprea Therapeutics, Cell Care Therapeutics, Dose Medical Corporation, Eyedaptic, Galimedix, Genentech, Glaukos, Interface Biologics, Iveric Bio/Ophthotech, jCyte, Novartis Pharmaceuticals, Ocunexus Therapeutics, Regeneron Pharmaceuticals, Re-Vana Therapeutics, Ripple Therapeutics and Theravance Biopharma.
August 18, 2021
11 min read

Cataract in patients with AMD: Thumbs up for surgery, with realistic expectations

Source: Healio Interviews
Disclosures: Devgan reports no relevant financial disclosures. Do reports she is a consultant for Boehringer Ingelheim, Genentech, Kodiak, Regenxbio and Santen. Hovanesian reports he is a consultant for Alcon, Bausch + Lomb, Johnson & Johnson and Carl Zeiss Meditec. Kuppermann reports he is a consultant for Allegro Ophthalmics, Allergan, Aprea Therapeutics, Cell Care Therapeutics, Dose Medical Corporation, Eyedaptic, Galimedix, Genentech, Glaukos, Interface Biologics, Iveric Bio/Ophthotech, jCyte, Novartis Pharmaceuticals, Ocunexus Therapeutics, Regeneron Pharmaceuticals, Re-Vana Therapeutics, Ripple Therapeutics and Theravance Biopharma.
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Age-related macular degeneration is the leading cause of vision loss in people older than 60 years in the United States, affecting an estimated 11 million to 15 million individuals.

Many of them in the course of the disease will also develop cataract, with consequent worsening of vision. In this event, a “holistic approach to vision” is required that takes into account both components and leads to decisions based on the patient’s realistic visual potential, dispelling unattainable expectations.

Baruch D. Kuppermann, MD, PhD
A patient’s comments regarding their vision issues should be a driving factor when deciding to recommend cataract surgery, according to Baruch D. Kuppermann, MD, PhD.

Source: Carlos Puma

“It is important for patients with macular degeneration to be given the full opportunity for rehabilitation, making sure we don’t leave any vision on the table,” retina specialist Baruch D. Kuppermann, MD, PhD, said.

The best approach is a team approach in which cataract and retina specialists evaluate the case together, establish the time frame for surgery and coordinate schedules.

“Understanding the patient’s AMD status can help the surgeon counsel the individual on their visual prognosis after cataract surgery. This is important because the underlying AMD may limit the potential for visual improvement, and patients need to be aware of this,” retina specialist Diana V. Do, MD, said.

Impact of surgery on AMD

In the past, concerns were raised by a number of cross-sectional studies about the potential of cataract surgery to increase the risk for incident AMD or the progression of preexisting AMD.

Diana V. Do, MD
Diana V. Do

Analysis of the combined data from the Salisbury Eye Evaluation, the Proyecto VER and the Baltimore Eye Survey consistently showed that previous cataract surgery was associated with an increased prevalence of late AMD. Pooled data from the Beaver Dam Eye Study and the Blue Mountains Eye Study found an association between cataract surgery and the 5-year incidence of AMD in patients with no AMD at baseline, and further analysis of the Beaver Dam Eye Study population found a substantial effect of cataract surgery on the incidence of late-stage AMD. However, other similarly large studies, including the Beijing Eye Study and the AREDS Report 25, found no significant evidence to support this correlation. Pooled data from the Singapore Malay Eye Study and Singapore Indian Eye Study populations found an overall low absolute risk for late AMD development, leading to the conclusion that “physicians should continue to balance the benefits and risks of cataract surgery in elderly patients.”

“It is a controversial topic, data are on both sides of the fence, and no consensus has been reached so far. However, it is worth noting that some of the studies were done in the older era of ECCE. In general, my sense is that cataract surgery does not increase the risk to a significant extent, so with proper patient selection, there is typically a net benefit to patients with macular degeneration in terms of long-term vision gain,” Kuppermann said.

Patients with AMD who develop cataract should be properly evaluated, and he encourages surgery when potentially visually significant cataracts are noted “because with proper selection the benefits outweigh the risks.”

The potential hypothesis of why cataract surgery may be harmful in the setting of AMD is twofold, Do said.

“On one hand, surgery can incite inflammation, which could upregulate the complement pathway, and the complement pathway has been implicated in the pathogenesis of AMD,” she said.

The other possible cause is blue light. In the Chesapeake Bay Waterman Study, a correlation was established between the high prevalence of advanced AMD and the exposure to high levels of blue light in the preceding 20 years.

“Ultraviolet or blue light has the potential to cause retinal phototoxicity. After a cataract is removed, more UV light can enter the eye. However, there is no evidence to date to prove that an intraocular lens is associated with increased risk of retinal phototoxicity from UV exposure,” Do said.

Given that recent studies and systematic reviews did not find any negative impact of cataract surgery on AMD progression, she believes that a patient with visually significant cataract and AMD should undergo surgery.

“I believe cataract surgery can safely be performed to improve the patient’s quality of life. Often, removing the dense cataract can improve the patient’s vision and also allow the ophthalmologist to monitor and evaluate the retina more easily,” she said.

“Since the leading cause of both AMD progression and cataract is age, it is very tempting to link one disease to the other, but most of us who do cataract surgery feel there is not a significant relationship,” OSN Cataract Surgery Section Editor John A. Hovanesian, MD, FACS, said.

John A. Hovanesian, MD, FACS
John A. Hovanesian

Healio/OSN Section Editor Uday Devgan, MD, said that in tens of thousands of surgeries over 20 years, he has never seen evidence of a causative relationship between cataract surgery and worsening of macular degeneration.

“In macular degeneration, the ball only rolls downhill. It’s not cataract surgery to make the macula worse. AMD progresses whether you do surgery or not,” he said.

Realistic approach, clear expectations

The decision of whether to perform surgery should be based on the evaluation of what percentage of the patient’s vision loss is due to AMD and what percentage is due to opacification of the lens, according to Devgan.

Uday Devgan, MD
Uday Devgan

“If you get a patient with mild cataract and a lot of macular degeneration, and you know that more than 90% of their visual complaints are due to macular degeneration, don’t do the cataract because that patient will be disappointed. The best candidates are those in which at least 50% of the visual limitation is cataract. Surgery will make their vision brighter and clearer, although the missing pixels and distortion in central vision cannot change,” he said.

Setting clear expectations is important because patients tend to unrealistically hope that vision will be back to normal after cataract surgery. They need to be educated on why this cannot be.

“I tell my patients that the eyes are like a camera, and cataract surgery changes the lens of the camera, but the film of the camera is the macula, and you cannot change the film. The key is setting appropriate expectations, and as long as you can meet them, they are going to be happy,” Devgan said.

Hovanesian also emphasized the importance of making patients understand what they can realistically expect from surgery.

“Patients are naturally inclined to hope that cataract surgery will give them back the normal vision they had before the onset of the disease, and this is not realistic. I try to give them a percentage improvement. If I think that 50% of the vision disability is due to macular degeneration, I say that cataract will improve things by 50%, and it could be anywhere from 30% to 70%. There will be some improvement from removing the cataract but no regain of normal vision,” he said.

Always something to gain

“The severity and stage of AMD are important to know before cataract surgery. Intermediate AMD is associated with drusen. Advanced AMD is defined as either wet AMD or dry AMD with geographic atrophy that affects the fovea. Understanding the patient’s AMD status can help the surgeon counsel the individual on what they can reasonably expect after cataract surgery,” Do said.

A patient’s comments on their vision problems are another driver to recommend cataract surgery and set realistic goals, Kuppermann said.

“Sometimes they describe difficulty at near but not at far. Sometimes they say colors have changed. I tell them they may not see more letters, but they potentially will perceive qualitative improvement, such as seeing clearer colors and brighter light,” he said.

In his opinion, patients with any sign of progressive vision loss, progressing cataract development and without obvious significant progression of the macular degeneration should be referred for surgery. But by and large, all patients for which macular degeneration is not the only cause of vision loss deserve to be considered.

“Even if it is 30% cataract and 70% macular degeneration, I would still suggest that they be considered for cataract surgery because they may benefit from it, and the risk of AMD progression is low,” Kuppermann said.

In most cases, surgery has an indication at the intermediate stages of macular degeneration, but even at the advanced stages of the disease, there may be good reasons to intervene and to make the best of peripheral vision.

“We are land-based creatures. Looking straight ahead is our most important visual field, but for these patients, the next most important visual field is down low to make sure they are not tripping over a curb. For the elderly people, tripping and breaking a hip is a downward death spiral. In patients with advanced macular degeneration and progressive cataract between the 2+ and 3+ grade, I think surgery is an important consideration in the hopes of improving and preserving their inferior visual field even when the benefit to their central visual field is minimal,” he said.

Timing of surgery and injections

The timing of cataract surgery in patients with wet AMD is crucial and may depend on how stable the exudative AMD lesion is.

“If the patient is receiving regular intravitreal anti-VEGF medicines and the wet AMD is under good control, then cataract surgery can be safely performed in between injection visits. Some colleagues have suggested administering an intravitreal anti-VEGF injection within 1 month of the cataract surgery to prevent any increased edema after surgery. Although there is no definite evidence to confirm the ideal timing of anti-VEGF injections before cataract surgery, the idea of maintaining good control of the exudative AMD lesion makes sense,” Do said.

In patients who are treated with injections at an interval shorter than 12 weeks, Kuppermann performs an injection 1 or 2 weeks before cataract surgery.

“This conceptually provides a molecular agent onboard at time of cataract surgery to prevent the increase of chemokines and cytokines and associated leakage of their wet AMD. Frequently, patients have cataract surgery in one eye and a week later they get it in the other eye, so that 1- to 2-week injection prior to first eye cataract surgery will cover them during the surgery of both eyes,” he said.

Concern was raised in the past that anti-VEGF might inhibit wound healing, but this is more of a theoretical risk, according to Kuppermann, and a 1-week window should be sufficient to dispel it.

A window of 1 week before surgery and a few weeks after surgery is advisable also to prevent adverse events, according to Hovanesian.

“Before, because there is always a little risk of endophthalmitis with injections, and after, because the eye needs to recover from the inflammation of surgery,” he said.

“The best is to work with the retina specialist. If they perform an injection a week or so prior to cataract surgery, I feel it is a benefit to have the anti-VEGF onboard at the time I do surgery,” Devgan said.

Pearls for surgery

Surgery in patients with a diseased macula does not differ from routine surgery but requires extra caution to avoid causing wide fluctuations in IOP and to keep the eye pressurized throughout the various steps, Hovanesian said.

“For example, giving some infusion through a side-port incision while you remove the I/A cannula prevents a significant sudden drop of pressure,” he said.

The most important precaution is to make sure there is no damage accidentally caused by intravitreal injections in the posterior lens capsule. It is a rare event, occurring in less than 1% of cases, but because millions of intravitreal injections are performed every year, every cataract surgeon experiences this at some point, Devgan said.

“Patients with AMD have multiple injections, and there is a chance that some of them will damage the lens capsule. I had many of such cases, and if a surgeon does not consider this possibility, intraoperatively the posterior capsule opens, and the nucleus falls in the vitreous. Before I operate on these patients, I look carefully at the posterior capsule with the slit lamp to make sure I don’t see any iatrogenic damage. Warning signs are patients who develop a pretty advanced cataract within a week or two of having an injection,” he said.

Kuppermann recommended OCT before cataract surgery to make sure there are no surprises related to the macula.

“It doesn’t require a retina specialist. Most comprehensive ophthalmologists as well as cataract surgeons have OCT in their office,” he said.

IOL selection

IOL selection in patients with macular degeneration is also a point of controversy. Monofocal IOLs are the safest and perhaps most sensible option, but some patients may still benefit from premium lenses to enhance near vision, according to Hovanesian.

“Presbyopia-correcting lenses are usually discouraged in patients with significant AMD because they degrade contrast sensitivity. This is a little less true with some of the newer EDOF lenses, but the benefit remains limited. We must evaluate the visual potential. If it is less than 20/25 or 20/30, I tend not to use a presbyopia-correcting lens,” he said.

However, in patients with early AMD, the benefit might be significant and remain so for a time long enough to motivate this choice.

“The average patient having cataract surgery in the U.S. is about 69 years old, and life expectancy on average is to about 79 years. So, the average patient has 10 years to live with their implant. I believe it is wrong not to offer a patient with early AMD a premium lens because patients want their best quality of life, they want it now, and even if AMD progresses, with treatment they will retain good enough vision to appreciate the benefits of these lenses,” Hovanesian said.

Devgan said he prefers monofocal IOLs to have the full quality of vision and to avoid the problems that may come when AMD progresses.

“Toric monofocal IOLs are good, but no multifocals, trifocals or EDOF. I want to focus all those photons right on the macula to give the best chance for good vision. And these patients are not super concerned whether or not they have to wear glasses,” he said.

As a retina specialist, Kuppermann does not generally recommend premium IOLs in patients with moderately severe or worse intermediate dry AMD because the benefits will be lost if the patient develops leakage or geographic atrophy. However, he leaves the ultimate decision to the cataract colleague.

“I have a discussion with the cataract surgeon. I do not exclude the possibility of multifocal lenses upfront. I just encourage the cataract surgeon to consider that choice in the context of the specific patient with macular degeneration being evaluated for cataract surgery,” he said.

Special lenses

The evidence that blue light-filtering IOLs protect the retina is not overwhelmingly convincing, according to Hovanesian.

“Some surgeons have strong feelings about this, but I do not. I tend to use lenses with no chromophores, so that they are clear,” he said.

“Blue-blocking lenses may offer some protection, but they slightly decrease the amount of light and may modify perceived color, and this is the tradeoff,” Kuppermann said.

In the early 2000s, Kuppermann was involved in reviewing the outcomes of the Implantable Miniature Telescope (IMT, VisionCare), a visual prosthesis that is implanted in place of an IOL to reduce the effects of the central scotoma by redirecting central vision images to undamaged parts of the retina surrounding the macula.

“The IMT is a mixed blessing. Some patients really benefit from it, but the IMT reduces the peripheral visual field, and for many patients this is very important. Other patients don’t know how to properly use the vision they regain centrally. It is difficult to predict who would benefit the most, so it is not easy to recommend. Additionally, the IMT implantation surgery is significantly different than typical modern IOL placement. I was in the OR during the implantation in some cases, and several times I was called to solve problems during surgery,” he said.

However, the interest in this technology has gradually been fading away over the years.

“I think the tradeoff was complicated, the learning curve was a bit challenging, and the benefits were not as great as we hoped for,” he said.

Click here to read the Point/Counter to this Cover Story.