Tactics for Better Patient Outcomes

by Brooke Herron

At the recently held 38th Asia-Pacific Academy of Ophthalmology Congress (APAO 2023) in Kuala Lumpur, Malaysia, ophthalmologists presented evidence-based diagnosis and treatment recommendations during a session titled, “Neovascular AMD Including Polypoidal Choroidal Vasculopathy.”

When it comes to neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), early detection and treatment are key to patient outcomes. As both pose serious threats to vision and quality of life, leading retina specialists placed an emphasis on their screening, diagnosis, and treatment in the final session of APAO 2023.

There are two important factors to reduce the societal burden of blindness due to macular degeneration, began Prof. Richard Gale. “One is to treat on time and early; and two, identify cases early.”

He shared data from the EDNA study, which found optical coherence tomography (OCT) to be the most accurate and cost-effective in diagnosing conversion to nAMD in the fellow eye.1

“Of course, we don’t know how often we should monitor or screen our patients, but perhaps every three to four months with OCT,” he said. “Healthcare institutions need to fund early treatment and early identification. This leads to better functional outcomes.”

To further reduce costs, Prof. Gale suggested combining diabetic eye disease and AMD screening. “Indeed, East Asia is leading the world in terms of the cost-effectiveness of combining diabetic and AMD screening,” he shared. Noting a paper from Hong Kong, he showed that this strategy is highly cost-effective.2 Timely, targeted screening also results in less fibrosis and smaller lesions, as well as the opportunity to identify geographic atrophy (GA) earlier, he added.

Antivascular endothelial growth factors (anti-VEGFs) are the go-to injections to treat both nAMD and PCV. However, which drug to use and how often to use it remains a hot topic. Thankfully, for best outcomes in treating PCV, Dr. Won Ki Lee has some straightforward strategies.

Aflibercept monotherapy is very effective in eyes with PCV, shared Dr. Lee. This is based on his involvement in the PLANET study, which showed improvement in visual and/or functional outcomes in more than 85% of participants treated with aflibercept monotherapy, with no signs of leakage from polypoidal lesions in more than 80%.3

He then made an important point when comparing PLANET with EVEREST II (which investigated ranibizumab monotherapy versus combination ranibizumab + PDT for PCV4). “When you look at the data for week 12, about 80% in PLANET achieved a dry macula; on the other hand, only 40% achieved a dry macula in EVEREST II [in the ranibizumab monotherapy arm],” Dr. Lee shared.

Although he admits that he doesn’t understand the fine print (i.e., drug molecules or kinetics) for this difference, he did offer some potential theories. “As a clinician, I could observe that the reduction of choroidal thickness is more frequent and permanent in cases treated with aflibercept. And I think this may contribute to better outcomes as

PCV is suggested to be driven by some choroidal changes,” he said.

“Previously, hyperpermeability of increased choroidal thickness was thought to be a negative factor — but many investigators revealed that aflibercept is also effective in eyes with choroidal vascular hyperpermeability and in pigment epithelial detachment (PED),” he continued. “And I think that drugs that have great effects on the choroid may also have additional therapeutic benefits on the pachychoroid.”

Further, Dr. Lee recommended that physicians take an individualized treatment approach with PCV patients, saying proactive regimens like treat-and-extend (T&E) are desirable. He noted that over 60% of patients can be extended to 12 weeks or beyond.

Nonadherence and treatment burden are top concerns in patients with nAMD — and as a result, more durable drugs that reduce injection frequency (while sustaining BCVA gains over time) are fueling pharmaceutical development in this space. One new drug on the block is faricimab, the first bispecific antibody for intraocular use that independently binds and neutralizes both angiopoietin-2 and VEGF-A.

“A lot of our drugs are very superior at drying, but we are struggling to find drugs that allow our patients to be extended longer so they don’t have to come to our clinic as frequently,” said Dr. Kenneth Fong. He was on hand to share the two-year results from the Phase 3 TENAYA and LUCERNE trials, which assessed the efficacy, safety and durability of faricimab versus aflibercept in patients with nAMD.5 The trial authors noted that “the decision to use aflibercept as a comparator aligned well with the findings from the 2020 American Society of Retina Specialists Preferences and Trends survey, which reported that aflibercept was the agent that retina specialists most commonly use as first-line therapy.”

According to Dr. Fong, patients in the faricimab arm achieved disease control with fewer injections over two years. He explained: “Faricimab achieved a greater reduction mean subfoveal thickness from baseline compared with aflibercept, allowing for rapid treatment interval extension in a majority of patients.”

Looking at a practical, clinical approach to treat and monitor nAMD was Dr. Barkeh Hanim Jumaat, who shared insights from her preferred treatment regimen.

Rather than a reactive protocol like PRN, a more practical, proactive approach is T&E which allows for treatment optimization, said Dr. Jumaat. “And treatment optimization leads to improved visual outcomes and reduced treatment burden.”

With T&E, she explained that injection intervals can be extended two to four weeks between visits, up to a maximum of 12 to 16 weeks — but this interval extension depends on the anti-VEGF agent used. “If it’s aflibercept, studies have shown that you can go up to 16 weeks; in ranibizumab or bevacizumab, you can do two-weekly increments up to 12 weeks,” said Dr. Jumaat. “The most important point in T&E is that injections should be given at every visit, even if the disease is inactive.”

If a patient is not responding to a particular anti-VEGF, Dr. Jumaat said she would take a conservative approach and consider a switch after five to six monthly injections. Before switching, she said it’s key to consider whether the treatment was aggressive, if the patient was monitored every q4w, or if the patient could be a delayed responder.

Of course, effective treatments and proactive regimens don’t mean much without an accurate diagnosis made with the right diagnostic equipment. Dr. Voraporn Chaikitmongkol explained that although indocyanine green angiography (ICGA) is the gold standard in diagnosing PCV, 66% of retinal centers in Thailand do not have ICGA.

However, the solution to this diagnostic quandary may lie in fundus photography (FP) and OCT. In fact, Dr. Chaikitmongkol has co-

authored a paper that explores the sensitivity, specificity, and predictive accuracy of potential diagnostic features detected using FP, OCT, and fluorescein angiography (FA) in diagnosing PCV without ICGA.6

The authors came up with four features that can be used to identify PCV — and if two of the four features are identified, a 95% sensitivity and 95% specificity for PCV diagnosis can be achieved. These include: 1) notched or hemorrhagic PED or fibrovascular PED on FP, 2) sharply peaked PED (angle 70-90 degrees) on OCT, 3) PED notch or multilobulated PED on OCT, and 4) hyperreflective ring underneath PED on OCT.

Next, she described how OCT features could provide high accuracy in identifying complete or incomplete polypoidal regression following treatment in PCV, highlighting data from another paper7 she co-authored. In this analysis, OCT characteristics of PED were classified by five prespecified features: A) no PED, B) PED with internal homogeneous reflectivity with predominant BUN (blended retinal pigment epithelium with underlying structure), C) PED with internal homogeneous reflectivity with minimal BUN, D) heterogeneous PED, and E) PED with hyporeflectivity. The results showed that the majority of patients who achieved complete polypoidal regression had features A (32%) or B (45%); meanwhile, 79% of those who had incomplete polypoidal regression had feature D.

1. Banister K, Cook JA, Scotland G, Azuara-Blanco A, Goulão B, Heimann H, Hernández R, et al. Noninvasive testing for early detection of neovascular macular degeneration in unaffected second eyes of older adults: EDNA diagnostic accuracy study. Health Technol Assess. 2022;26(8):1-142.

2. Chan CKW, Gangwani RA, McGhee SM, Lian JX, Wong DSH. Cost-Effectiveness of Screening for Intermediate Age-Related Macular Degeneration during Diabetic Retinopathy Screening. Ophthalmology. 2015;122(11):2278-2285.

3. Lee WK, Iida T, Ogura Y, Chen SJ, Wong TY, Mitchell P, Cheung GCM, et al. Efficacy and Safety of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in the PLANET Study: A Randomized Clinical Trial. JAMA Ophthalmol. 2018;136(7):786-793.

4. Lim TH, Lai TYY, Takahashi K, Wong TY, Chen LJ, Ruamviboonsuk P, Tan CS, et al. Comparison of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: The EVEREST II Randomized Clinical Trial. JAMA Ophthalmol. 2020;138(9):935-942.

5. Khanani AM, Guymer RH, Basu K, Boston H, Heier JS, Korobelnik JF, Kotecha A, et al. TENAYA and LUCERNE: Rationale and Design for the Phase 3 Clinical Trials of Faricimab for Neovascular Age-Related Macular Degeneration. Ophthalmol Sci. 2021;1(4):100076.

6. Chaikitmongkol V, Kong J, Khunsongkiet P, Patikulsila D, Sachdeva M, Chavengsaksongkram P, Dejkriengkraikul C, et al. Sensitivity and Specificity of Potential Diagnostic Features Detected Using Fundus Photography, Optical Coherence Tomography, and Fluorescein Angiography for Polypoidal Choroidal Vasculopathy. JAMA Ophthalmol. 2019;137(6):661-667.

7. Chaikitmongkol V, Chaovisitsaree T, Patikulsila D, Kunavisarut P, Phasukkijwatana N, Watanachai N, Choovuthayakorn J, et al. Optical Coherence Tomography Features for Identifying Posttreatment Complete Polypoidal Regression in Polypoidal Choroidal Vasculopathy. Asia Pac J Ophthalmol (Phila). 2022;11(5):408-416.

8. Tan CS, Ngo WK, Lim LW, Tan NW, Lim TH; EVEREST Study Group.

“Complete polypoidal regression is another important anatomical outcome for PCV treatment because it’s related to fewer recurrences, longer disease inactivity… and many studies have found that we will need less frequent injections,” said Dr. Chaikitmongkol.

While there are certain characteristics associated with PCV — that doesn’t mean it’s always PCV. According to Dr. Gemmy Cheung, some of these masquerading features include blood, multilobulated or peaked PEDs, subretinal fluid and thick choroid, and focal nodular hypofluorescence.

In one example, Dr. Cheung shared patient images (FP, OCT, and ICGA) showing blood — which, at first glance, could be mistaken for PCV. “This is actually a hypertensive patient with a macroaneurysm, which is also one of the common reasons for retinal hemorrhages,” she explained.

“In the past, it was very easy to make this mistake, but when combining with OCT you can see that this is predominantly a preretinal hemorrhage and there is no PED. So this should alert us that while there is a lot of blood, it is not likely to be PCV-related,” said Dr. Cheung, adding that blood from large RPE tears may also be unrelated to PCV. In addition, she recommended reading the Everest study8 on this topic, which describes some of the “famous pseudo-polyps” to look out for.

The 38th Asia-Pacific Academy of Ophthalmology Congress (APAO 2023) was held on February 23 to 26 in Kuala Lumpur, Malaysia. Reporting for this story took place during the event.

Data from the US LIGHTSITE III clinical trial are in — and the results are good. Indeed, LumiThera (Poulsbo, Washington, USA) recently announced that early to intermediate dry AMD patients treated with photobiomodulation (PBM) therapy using the Valeda® Light Delivery System demonstrated sustained vision improvement for 24 months.

A prospective, double-masked, randomized, multi-center clinical trial, LIGHTSITE III took place at 10 US retinal centers and enrolled 100 subjects with early to intermediate dry AMD. Patients’ eyes were treated every four months with Valeda; the final treatment occurred at month 21 with the last follow-up visit at month 24. Investigators’ primary efficacy endpoint was best corrected visual acuity (BCVA).

The investigators noted minimal safety

risks and high compliance with 80% of patients completing the 24-month trial. In total, there were 91 eyes in the PBM-treatment group and 54 in the sham-treatment group. At 24 months, the BCVA improvement from baseline in the PBM group was significantly greater than the sham group, 5.9 vs 1.0 letters (p = 0.0015). Further, approximately 58% of the PBM-treated eyes had >5 letter gain, with a mean increase of 8.5 + 0.5 letters. Eyes in the PBM group demonstrated this improvement at month 21 (after the last treatment); this was sustained throughout the trial’s conclusion at month 24.

During the trial, patients also underwent detailed retinal morphology analysis using OCT. Dr. Glenn Jaffe, a vitreoretinal surgeon and professor of ophthalmology at Duke University Eye Center, explained that fewer eyes progressed to new geographic atrophy. The 24-month OCT data indicated that five of 88 eyes (5.7%) in the PBM group progressed to new GA, whereas 11 of 51 eyes (21.6%) in the sham arm developed new GA.

“PBM treatment showed a statistically significant (p = 0.003) slowing of disease progression in patients with early to intermediate dry AMD,” stated Dr. Jaffe.

Not only is PBM treatment a significant advancement in saving sight for AMD patients, but it’s also non-invasive, explained Dr. Diana V. Do and Dr. Quan Dong Nguyen. Both Dr. Do and Dr. Nguyen are members of the Retina Division at the Byers Eye Institute at Stanford University, one of the clinical sites for LIGHTSITE III. “We are in urgent need of therapy for our patients with dry AMD, especially if the treatment is non-invasive such as the Valeda Light Delivery System,” they said.

Bionic eyes (or visual prostheses) create a sense of vision and light perception for those with advanced vision loss — and the ability to restore any semblance of sight is a gift for those affected by sight-threatening eye disease.

The need for these advanced medical devices is only going up: A recent market study by Fact.MR predicts the demand for bionic eye technology to rise at a CAGR of 13%, increasing the global market value from US$297.1 million in 2023 to US$1 billion in 2033. The recently released report detailed some key factors driving this rapid growth, including recent innovations and the higher prevalence of eye disease leading to vision loss.

According to a Fact.MR analyst, rapidly increasing older populations who are more prone to eye disease, along with the rising prevalence of diabetic retinopathy, are contributing to the demand for bionic eye technologies.

Further, innovation in the technology itself has led to an uptick in uptake — today’s bionic eyes provide better vision, and they’re more comfortable to use. One such example is the Argus II Retinal Prosthesis System from Second Sight Medical Products, Inc., which allows patients to perceive light patterns and images via a wireless implantable device that provides electrical stimulation to the retina. Bionic eye solutions are also more affordable, thanks to dedicated investment into research and development from key industry players.

In addition, the researchers found that bionic eye tech is booming in three regions in particular. In the United States, well-established healthcare facilities and key market players are driving sales. Meanwhile, in Germany, the older population is the primary factor for increased demand. In addition, the market is also expanding in Australia, thanks to its advanced medical technologies and researchers.