Published in Retina

Complement Inhibition and Patient Selection

This is editorially independent content supported by advertising from Apellis Pharmaceuticals
10 min read

In this episode of Clinical Conversations in Retina, Daniel Epshtein, OD, FAAO, reviews tips for selecting patients for complement inhibition treatments with Deep Parikh, MD.

In the third installment of Clinical Conversations in Retina, Daniel Epshtein, OD, FAAO, sits down with Deep U. Parikh, MD, a retina and uveitis specialist, to discuss patient selection pearls for complement inhibition treatments to manage geographic atrophy (GA).

Selecting patients for complement inhibition treatments

Dr. Parikh explained that every individual retina specialist has a unique approach to identifying patients for complement inhibition treatments because these medications are still relatively new. Some specialists do not offer the treatments at all, while others offer them to most, if not all, GA patients.
Additionally, the data suggests that these drugs can be effective at slowing down the progression of GA, so in his professional medical opinion, at the moment, it would currently be best to offer complement inhibition treatments to patients at the highest risk of progression.
Patients at the highest risk of progression to GA include those with:
  • Large lesions at baseline
  • Multifocal GA
  • Bilateral disease/fellow eye status
  • Extrafoveal GA
These patients are more likely to be motivated to undergo treatment as they are at high risk for vision loss. Further, patients who are smokers, have a family history of age-related macular degeneration (AMD) and/or GA, and subretinal drusenoid deposits should be closely monitored as they are still at risk of progression.1

Imaging modalities to identify and monitor GA

The existing rate of GA progression and visual function are key factors to consider when evaluating patients for AMD and GA, explained Dr. Parikh.
The imaging modality that he tends to lean on the most is optical coherence tomography (OCT) and near-infrared reflectance (NIR) imaging on the OCT because the machine is accessible in most clinics and is useful for identifying incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) or complete RPE and outer retinal atrophy (cRORA).
On OCT, Dr. Parikh recommended looking for light hypertransmission of the choroid. He also uses microperimetry and fundus autofluorescence (FAF) to identify GA and monitor patients. Unfortunately, he lamented these modalities tend to be less accessible to eyecare practitioners (ECPs) who are not retina specialists.

Deciding when to refer GA patients

As an optometrist, Dr. Epshtein highlighted that he is accustomed to monitoring GA patients in the office, usually two to three times a year. However, this treatment paradigm is slowly shifting because of the advent of GA treatments. As he explained, there are many optometrists and comprehensive ophthalmologists who have begun to navigate a more proactive practice pattern with an increased frequency of retina referrals.
With the two available treatments for GA, Dr. Parikh emphasized the importance of early detection and referral to retina specialists, particularly for patients at high risk of GA progression. This is especially true for patients who currently have intermediate AMD and some of the risk factors listed earlier (i.e., smoking or family history), as it is beneficial to refer them early.
In this manner, a retina specialist is able to record a baseline measurement for perimetry, OCT, and/or FAF and discuss how their GA has the possibility of progressing and the level of impact on their vision. Doing so allows ECPs to expedite the treatment process to potentially mitigate disease progression.
Dr. Epshtein noted that if you do not have access to specific instrumentation at your disposal, it is recommended to refer the patient for more imaging to ensure that GA and AMD progression is detected as early as possible. Dr. Parikh added that in his clinical experience, patients with extrafoveal disease sometimes do not understand the impact of the disease on their vision because, over time, their brain adapts to compensate for areas of vision loss.

Information to convey to a retina specialist when referring a GA patient

Dr. Parikh explained that when a patient is referred to him, he prefers to get a combination of a patient summary that outlines how long the clinician has been seeing the patient and why they are being referred, as well as sending recent OCT imaging of any concerning findings.
He added that it is important for retina specialists to understand the rate of progression for the patient, and a single OCT image only captures a snapshot of the patient’s condition, so providing contextual information gives him a better picture of the case while evaluating the patient to understand how quickly the disease is progressing.

Overview of a monthly complement inhibition treatment visit

Next, Dr. Epshtein asked Dr. Parikh to review what a typical complement inhibition treatment visit looks like. Dr. Parikh remarked that at his clinic, there is a long-standing protocol for wet AMD management that they have adjusted to fit GA patient needs.
In general, patients come to the office and undergo OCT imaging, which is then reviewed and followed by intravitreal anti-vascular endothelial growth factor (VEGF) treatment, if medically necessary. While GA patients tend to have a similar treatment regimen, there tends to be more testing involved, such as FAF, microperimetry, and OCT angiography (OCTA), to record baseline measurements.
When the patient comes in for monthly injections, Dr. Parikh usually relies on OCT and NIR imaging to guide his treatment decision-making. Then, every 3 to 6 months, Dr. Parikh repeats their microperimetry and FAF to get a sense of their progression or lack thereof. While he initially performed FAF on GA patients every month, he realized that there was not much utility in this because the condition progresses slowly enough that month-to-month, there was not enough change for him to measure.

Incorporating OCTA into the GA treatment paradigm

Dr. Epshtein mentioned that many ECPs have begun to use OCTA to monitor and evaluate vascular diseases, such as neovascular AMD (nAMD). Generally, Dr. Parikh uses OCTA when he suspects that there might be macular neovascularization (MNV) developing, and if it doesn’t provide him with the information he needs, he then turns to fluorescein angiography (FA). He finds OCTA most helpful for monitoring rates of MNV in patients currently undergoing complement inhibition treatments.
Due to the fact that both complement inhibitors have been associated with increased rates of MNV, Dr. Parikh tends to get a baseline OCTA for all GA patients and then re-orders OCTA if any changes are noted in vision, retinal exam, or on other imaging modalities while patients are undergoing treatment. Otherwise, Dr. Parikh does not perform OCTA imaging on GA patients regularly.
In comparison to wet AMD patients, there are many more imaging modalities required to monitor and identify GA patients because there are more factors clinicians need to check for, added Dr. Parikh. Most retina practices are streamlined to manage wet AMD, so treating GA requires them to add more time to their initial evaluations and follow-up appointments. As such, they are currently fine-tuning their workflow for managing GA patients.

Adverse events associated with complement inhibition treatments

There have been reports of these treatments resulting in increased rates of MNV, which clinicians can closely monitor with OCT while patients come in for injections.1 Additionally, ocular inflammation and occlusive and non-occlusive vasculitis have been reported, though the number of patients that experience these side effects remains low.2
Dr. Parikh noted that this means retina specialists need to be vigilant in identifying these potential adverse events and quickly treating them.

How do complement inhibitor treatments/GA impact nonexudative MNV?

Nonexudative MNV is a relatively new type of condition that can be identified and monitored due to the advent of OCTA. As time goes on, clinicians will likely better understand when specific patients develop MNV due to the complement inhibition treatments and which MNV are exudative versus nonexudative.
Dr. Epshtein conjectured that nonexudative neovascular membranes can act as a surrogate choriocapillaris, feeding nutrition to the RPE and outer retina. If they start leaking or growing too much, patients could undergo anti-VEGF therapy to prune down the membrane so that it does not reduce visual function.

Conclusion

Thoroughly understanding the merits and complications of complement inhibitor treatments along with patient selection is helpful for not only retina specialists but optometrists and referring ophthalmologists as well.
GA patients need close monitoring, so having a team approach to managing them is key to providing high-quality patient care.
  1. Tzoumas N, Riding G, Williams MA, et al. Complement inhibitors for age-related macular degeneration. Cochrane Database Syst Rev. 2023;6(6):CD009300. doi:10.1002/14651858.CD009300.pub3
  2. Apellis Pharmaceuticals. Apellis Provides Update on Review of Rare Safety Events with SYFOVRE® (pegcetacoplan injection) for Geographic Atrophy. Published  July 29, 2023. Accessed August 18, 2023. https://investors.apellis.com/news-releases/news-release-details/apellis-provides-update-review-rare-safety-events-syfovrer.
Daniel Epshtein, OD, FAAO
About Daniel Epshtein, OD, FAAO

Dr. Daniel Epshtein is an assistant professor in the ophthalmology department of Mount Sinai Morningside in New York City. Previously, he held a position in a high-volume multispecialty ophthalmology practice where he supervised fourth-year optometry students as an adjunct assistant clinical professor of the SUNY College of Optometry. Dr. Epshtein’s research focuses on using the latest ophthalmic imaging technologies to elucidate ocular disease processes and to simplify equivocal clinical diagnoses. He developed and lectures in the perioperative care course at the SUNY College of Optometry. Dr. Epshtein writes and lectures on numerous topics including glaucoma, retinal disease, multimodal imaging, ocular surface disease, and perioperative care.

Daniel Epshtein, OD, FAAO
Deep U. Parikh, MD
About Deep U. Parikh, MD

Dr. Deep Parikh, M.D. is a distinguished specialist in the field of Medical Retina and Uveitis. He maintains a private practice at Gentile Retina New York City and Long Island and is honored to hold the position of Adjunct Assistant Professor and Clinical Instructor at New York Eye and Ear Infirmary of Mount Sinai where he is actively involved with teaching Ophthalmology residents and fellows, Adjunct Assistant Professor at NYU Long Island School of Medicine, and Adjunct Assistant Professor at SUNY College of Optometry.

His clinical focus on uveitis and retina disorders reflects a deep commitment to addressing complex ocular conditions. Renowned for his patient-centered approach, Dr. Parikh combines his advanced medical knowledge and training with empathetic care to provide comprehensive solutions for his patients. His exceptional communication skills enable him to share intricate medical concepts with both peers and the public, making him a highly sought-after speaker. Dr. Parikh's passion for clinical research signifies his commitment to staying at the forefront of medical advancements and providing his patients with the best possible care informed by the latest insights and innovations.

Deep U. Parikh, MD
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