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In nAMD treatment... which option is the best?
Assessing the Options
in nAMD Treatment by Brooke Herron
Anti–vascular endothelial growth factor (anti-VEGF) therapies dramatically changed the prognosis of neovascular age-related macular degeneration (nAMD), when before we only had photodynamic therapy (PDT), began Dr. Patricia Udaondo from the Hospital Universitario y Politécnico de La Fe in Valencia, Spain.
Today, nAMD is often managed with intravitreal anti-VEGF injections. And as ground-breaking as these agents are, the treatment burden can be high for both patients and physicians — especially for those on fixed monthly dosing.
Thanks to the high burden, regimens like treat-and-extend (T&E) are gaining steam: “T&E strikes a balance between the benefits of a fixed regimen and the desire for physicians to individualize based on specific response,” said Dr. Udaondo. “This reduces the cost of treatment and gets vision outcomes closer to that in clinical trials.”
In addition, new treatments, like longerlasting anti-VEGFs and gene therapy are making waves. These updates and more were discussed during the Subspecialty Day: Management of Age-related Macular Degeneration session on the second day of the 37 th World Ophthalmology Congress (WOC2020 Virtual®).
Bevacizumab isn’t going anywhere
“Will bevacizumab still be used for management of wet AMD five years from now?” asked Dr. Baruch Kuppermann from the Gavin Herbert Eye Institute, University of California Irvine, USA. Although bevacizumab is off-label, it’s often used over approved anti-VEGFs due to its low cost and non-inferiority to other agents. According to Dr. Kuppermann, in 2018, the average wholesale cost for ranibizumab was $1950; aflibercept was $1850. Meanwhile, bevacizumab sits at $50 per dose.
Also, Dr. Kupperman noted that biosimilars (in development for ranibizumab) won’t be able to compete with bevacizumab either, when it comes to cost and cost effectiveness. “We will continue to have bevacizumab as a strong weapon in our armamentarium in the fight against wet AMD for the foreseeable future,” he concluded.
Safety concerns rock the boat for brolucizumab
Brolucizumab entered the market buoyed by results of efficacy and reduced injection frequency. Then the American Society of Retina Specialists (ASRS) alerted the ophthalmic community of 14 cases of retinal vasculitis. However, as serious these side effects are, physicians aren’t quite jumping ship yet.
“Before the new safety concern, we had contemplated moving to brolucizumab as a first-line therapy,” said Dr. Srinivas Sadda, from the Doheny Eye Institute UCLA, California. He detailed several patient cases where brolucizumab resulted in better outcomes than other agents. “It appears to have superior drying and consequently, superior durability over other currently available agents. risks. We are considering the treatment for patients who cannot be extended and who cannot come more frequently, and whose fellow eyes have reasonably good vision,” he continued.
“If we’re able to predict who is going to get the inflammation, or if we’re able to get insight into why the inflammation is occurring and can manage it or prevent it, then that will obviously impact our utilization,” explained Dr. Sadda.
It’s all in the genes
Gene therapy is showing promise for treating nAMD, said Dr. Allen Ho from Wills Eye Hospital, Pennsylvania, USA. During his presentation, Dr. Ho discussed phase I/II trial results for a new therapy from Regenxbio using subretinal delivery, dubbed as RGX-314.
Results showed that RGX-314 was well-tolerated at all dose levels, reported Dr. Ho. In cohort 3, there was a longterm, durable treatment effect for over two years, resulting in improved VA and stable retinal thickness. It also significantly reduced the treatment burden. In cohort 5, 73% of patients remained anti-VEGF injection-free at 9 months.
Could gene therapy rally to the frontline of nAMD treatment soon? We can’t predict the outcomes, but it certainly looks promising.
Dr. Patricia Udaondo
Hospital Universitario y Politécnico de La Fe Valencia, Spain
Corneal Surface Disorders
Smoothing Things Over
by Sam McCommon
There’s nothing corny about corneal health.
Day two of the 37 th World Ophthalmology Congress (WOC2020 Virtual®) continues, and one of the morning’s live sessions tackled cornea diseases. Keratoconus was one of the major focuses, as was a more rare condition involving an amoebic infection in the cornea.
Looking for keratoconus clues
Dr. Jesper Hjortdal from Aarhus University in Copenhagen, Denmark, presented an eye-opening view into potential signs of keratoconus. The etiology and onset of keratoconus has been mysterious for some time, although the medical community is aware that sex hormones play a role in maintaining the structure of the cornea.
He shared data that indicated social demographic factors: of patients presenting with keratoconus, two-thirds were male while non-Europeans had a three times higher risk factor than Europeans. Single people had a 27% higher risk and those in the cities had a significantly lower risk than those living in the countryside. Additionally, asthma and atopic dermatitis were associated with keratoconus but surprisingly diabetes was not associated, according to the study.
He continued on to point out that he believes prolactin-induced protein (PIP) is a viable biomarker for keratoconus, and noted that PIP levels are regulated by androgens and estrogens. PIPs are found in many secretions in the body, including saliva, and can affect the corneal surface.
Most specifically, he indicated that lower PIP levels than normal can be a biomarker for keratoconus. If so, this can be a landmark change in the way keratoconus is understood and predicted. Certainly, having many biomarkers would be ideal, but having a good measuring stick is a solid start.
Acanthamoeba keratitis
Dr. Sajjad Ahmad, of Moorfields Eye Hospital in London, United Kingdom, took on a rare but dangerous condition: acanthamoeba keratitis (AK). As the name suggests, the condition occurs when amoeba of the acanthamoeba genus invade the cornea.
The amoeba can be contracted in water, with hard water presenting a three times greater risk of exposure than soft water. Dr. Ahmad recommended that those with contact lenses should avoid wearing them while swimming and showering to reduce the risk of infection.
The disease is notoriously difficult to cure, with a median treatment time of five to six months. It can lead to infection, inflammation, epithelial loss, IOP fluctuations and even cataracts. The main drug used to treat it is biguanide, which is sometimes paired with diamidine for a dual treatment. However, Dr. Ahmad noted that evidence for the effectiveness of a dual treatment is lacking, and that diamidine’s toxicity is a problem.
Even with medical treatment, Dr. Ahmad said there is a 50% chance of poor outcomes, including poor vision and a further need for surgery.
Early diagnosis is crucial, as severe AK has a high level of vision morbidity. Dr. Ahmad recommends treating with antiamoebics before using topical steroids, and commented that a quarter of patients don’t need topical steroids, but around two-thirds will need systemic immune suppression.
Keratoplasty is an option only when medical treatments have been optimized and still failed, emphasized Dr. Ahmad. In this circumstance, it’s a risky procedure, with a risk of recurrence, a failure to heal, secondary glaucoma or hypotony are all potential outcomes. Two-thirds of patients will require regrafts and three-quarters will require other surgery — all with vision outcomes ranging from 20/20 to blindness.
Because it can be painful as well, non-steroidal anti-inflammatory drugs (NSAIDs) for chronic pain and sedatives for nighttime relief may be required. There’s even a mental health support group for the condition because it can affect one’s life so much.
The condition certainly doesn’t sound pleasant, but it’s good to know that even for such a case treatments are available.
Imaging the Optic Nerve, Lamina Cribrosa and Retina in Glaucoma
by Joanna Lee
is typically only slowly progressive, and has no agreed upon standard for diagnosis.” This statement from the Agency for Healthcare Research and Quality (AHRQ) provides an overview of the ongoing challenges in diagnosing the disease. Nevertheless, ongoing investigations are helping to shed more light on the parameters of its diagnoses.
Imaging in glaucoma
In a WOC2020 Virtual® presentation titled Practical Recommendations for Imaging in Glaucoma, Dr. C. Gustavo De Moraes from Columbia University, New York, USA, mentioned among his many tips to always look at the global and local matrix when looking for progression as they complement each other. He also recommended to look at individual scans and compare them with the visual field (VF). To lower false which suggested a rate progression of 0.9 μm/year would be useful to define progressive cases. As glaucoma occurs mostly in the superior and anterior poles of the disc, he also said it’s important to look for changes in these locations (on the topographical map). Dr. Moraes also shared his study’s findings 2 where he and his coinvestigators found a method to gauge the agreement between structural (optical coherence tomography [OCT]) and functional (visual field [VF])
“Screening for glaucoma is a difficult problem because it is asymptomatic, has low prevalence,
positive rates, Dr. Moraes cited a study 1
glaucomatous damage.
The roles of OCT and OCTA
In presenting Pearls and Pitfalls of Optical Coherence Tomography (OCT), Dr. Xiulan Zhang from Zhongshan Ophthalmic Center, China, highlighted a few factors which would affect the image quality when trying to determine the real “thinning of the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL). Some of the factors include signal quality, scan alignment, opacities, segmentation errors and aging. She also highlighted improvements which are needed in optical coherence tomography angiography (OCTA) imaging. “Going wider and deeper is needed in OCT and OCTA scanning of glaucoma subjects,” she said.
Eyes with high myopia are difficult to diagnose, as expounded during a presentation on Myopia Optic Nerve Imaging for Myopic Glaucomatous Eyes. Dr. Kyung Rim Sung from the University of Ulsan College of Medicine at Asan Medical Center in Seoul, Korea, spoke on the possibilities of using OCT to diagnose and note the progression of the myopic glaucomatous optic disc. “Some of the myopic optic disc has deformation in its shape, having many variables; but when we look at the optic disc for glaucomatous change, we have to be careful of the neural retinal rim, RNFL and vessel position changes,” she explained.
Using trend-based analysis of the GC-IPL change in thickness on the OCT, Prof. Jin Wook Jeoung from the Seoul National University Hospital in South Korea, in his presentation titled Progression Analysis in Glaucoma Using Macular OCT Scan found that the GCIPL thinning rate of the temporal sector was faster in the affected than in the unaffected hemifield. This suggests that glaucomatous damage may progress locally in a specific sequence. This type of trend-based analysis may be used for assessing glaucoma progression objectively and quantitatively. In another study, the integration of RNFL and GCIPL maps looks promising for detecting structural progression in patients with early glaucoma.
Optic disc hemorrhages are usually overlooked in clinical examinations. Dr. Zeynep Ozturker from Baskent University in Turkey, in her presentation on Optic Nerve Hemorrhages in Glaucoma - What You Need to Know said that digital imaging devices are not capable of detecting disc hemorrhages (DHs). The presence of DHs is a risk factor for normal tension glaucoma (NTG) progression as well as primary openangle glaucoma (POAG) and they usually precede RNFL thinning. It can occur despite good intraocular pressure control. Disc photography, OCT and VF tests as a part of follow-ups, are vital for patients with DH.
Lest we forget: AI
Finally, during the Artificial Intelligence and the Future of Imaging in Glaucoma presentation, Dr. Naama Hammel from Google shared on her team’s effort to develop and put in place validations of an algorithm to predict glaucoma. 3 Although the model used fundus photography instead of OCT, her presentation provided insights into building models for deep learning. Her team, having worked on a previous model for diagnosing diabetic retinopathy, have found that high quality “ground truth data” is the “secret sauce” while validation and generalization is key in creating models the machines can learn.
References:
1
2 Saunders LJ, Medeiros FA, Weinreb RN, Zangwill LM. What rates of glaucoma progression are clinically significant? Expert Rev Ophthalmol. 2016; 11(3): 227–234. Hood DC, Tsamis E, Bommakamti NK, et al. Structure-Function Agreement Is Better Than Commonly Thought in Eyes With Early Glaucoma. Invest Ophthalmol Vis Sci. 2019; 60(13): 4241–4248.
3 Phene S, Dunn RC, Hammel N, et al. Deep Learning and Glaucoma Specialists: The Relative Importance of Optic Disc Features to Predict Glaucoma Referral in Fundus Photographs. Ophthalmology. 2019;126(12):1627-1639.
Early Vitrectomy for
retinopathy (DR) is a major topic that Dr. Maria Berrocal from San Juan, Puerto Rico, presented a potential paradigm shift in the treatment of diabetic retinopathy: practicing early vitrectomy. As it stands, 60% of diabetics develop progressive diabetic retinopathy (PDR) and of those 50% will suffer severe vision loss. She noted that panretinal photocoagulation (PRP) reduces severe vision loss to 4%, but that despite PRP
5% of patients will still require vitrectomy. Diabetic Retinopathy? PRP has been by Sam McCommon considered the gold standard for DR
Diabetic retinal disease was another not ideal. Dr. Berrocal said that the topic covered on day two of the treatment can lead to severe visual 37 th World Ophthalmology Congress field defects and night vision loss. (WOC2020 Virtual®). As one of the Furthermore, many eyes still progress to leading causes of blindness, diabetic tractional retinal detachment (TRD). will unfortunately continue to grow in The crux of the presentation was Dr. importance concurrently with increasing Berrocal’s assertion that early vitrectomy rates of diabetes. is the best prevention compared to PRP.
treatment but is In an 8-year follow-up study comparing PRP and vitrectomy — in which one eye underwent PRP and the other vitrectomy — the outcomes clearly favored vitrectomy. Vitrectomized eyes had a mean postoperative visual acuity of 20/80, compared to 20/400 for PRP-treated eyes. Similarly, 88% of the vitrectomized eyes showed improvement in visual acuity in contrast to only 24% of the PRP-treated eyes. Twenty percent of eyes treated by PRP still had no light perception after the treatment.
Postoperative procedures necessary told a similar tale. Over eight years, 16% of the vitrectomized eyes in patients younger than age 50 needed additional laser treatment, 12% needed a reoperation, and 40% needed a cataract operation. In comparison, 72% of PRPtreated eyes needed laser surgery, 60% needed a vitrectomy, and 72% developed TRD, of which 16% was inoperable.
A study of patients older than 50 bore similar results, with even fewer patients needing laser treatment or reoperation.
Dr. Berrocal stressed the importance of understanding a patient’s needs, and just how vitrectomy can address them. Many working-age diabetics don’t have time to visit their ophthalmologist often, which treatments like ranibizumab require. What’s more, many diabetics are uninsured or underinsured, and may be burdened by the cost of treatment. Most importantly, she concludes, vitrectomy may be able to save many eyes –especially among young diabetics.
WE STAND WITH THE WORLD OF OPHTHALMOLOGY
during this time of challenge, and also of hope. All around the globe we stand united with colleagues, organizations, ophthalmologists and industry, to make 2020 and beyond what it should be: Clearly, a better future.
In partnership with:
Reducing Rotation in Toric IOLs
by Brooke Herron
Toric intraocular lenses (IOLs) provide excellent visual acuity and high patient satisfaction by reducing or eliminating astigmatic error. However, residual error may happen and that impacts the expected clinical results, shared Prof. Boris Malyugin from the S. Fyodorov Eye Microsurgery Federal State Institution in Moscow, Russia.
Residual error as a result of rotation can severely impact visual outcomes: A 30-degree rotation results in 100% cylinder power loss, while a 90-degree rotation doubles the astigmatism.
“Eighty-five percent of postoperative rotation occurs within the first hour,” said Dr. David Chang, from the University of California, San Francisco, USA.
Therefore, tips to optimize outcomes were shared by these experts and others, during a session titled Toric Implantation in Your Routine Practice on the second day of the 37 th World Ophthalmology Congress (WOC2020 Virtual®).
Pearls for avoiding rotation
Toric IOLs can rotate during surgery or postoperatively. To avoid this, Dr. Chang provided six pearls:
Use a non-dispersive OVD: “I don’t want the lens to be slippery.”
Remove OVD behind IOL: “Then I try to go behind the lens to evacuate the viscoelastic to improve contact between the posterior capsule and the lens.”
Digital alignment: “I use Callisto (Carl Zeiss Meditec, Jena, Germany) to digitally align, and that helps me avoid surgical misalignment.”
Nasal placement: “I tend to place the lens on the nasal part of the capsular bag, this is done anyway to center the visual axis of these diffractive lenses...”
Like tortoises, IOLs can sometimes rotate in the wrong direction. . .
5. Leave the eye soft: “I don’t overinflate the bag while I’m inflating the anterior chamber.”
6. Tell patients to minimize activity: “I tell them not to do a lot of walking, to do a lot of sitting, I try to minimize their activity C for the rest of that operative day.”
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Even with these pearls, sometimes rotation is unavoidable: “Rotating the
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MY IOL is something you’re going to have to do sooner or later if you do a lot of toric IOLs — but particularly if you’re going
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CMY to do presbyopia correcting toric IOLs,” shared Dr. Chang.
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Other tips and tricks
“My personal opinion is that we probably use toric IOLs too little today as they are a great way to correct astigmatism,” said Dr. Anders Behndig from the Department of Clinical Sciences/Ophthalmology at Umeå University Hospital in Sweden.
He also provided some tips regarding toric IOLs — for example, pure myopic astigmatism is better than mixed astigmatism: “You’re better off making the patient a little bit myopic, than a little bit hyperopic,” he explained. “There are also changes from with-therule-astigmatism (WTR) to against-therule-astigmatism (ATR) with increasing age.”
Further, Prof. Malyugin noted that digital marking seems to be superior to manual marking when it comes to the proper alignment of the lens intraoperatively, and that certain surgical techniques can improve the stability and position of toric IOLs.
We Stand We Stand With The World of With The World of Ophthalmology Ophthalmology
during this time of challenge, during this time of challenge, and also of hope. and also of hope.
All around the globe we stand All around the globe we stand united with colleagues, united with colleagues, organizations, ophthalmologists organizations, ophthalmologists and industry, to make 2020 and and industry, to make 2020 and beyond what it should be: beyond what it should be:
