Introduction
Geographic atrophy (GA) is a progressive eye condition characterized by the degeneration of retinal cells, leading to irreversible vision loss predominantly among older adults. It represents the advanced form of dry age-related macular degeneration (AMD), which is a leading cause of blindness globally. With an aging population worldwide, GA poses a growing public health challenge and a significant burden to patients and healthcare systems alike.
While new therapies, such as intravitreal complement inhibitor injections (IVCIs), have demonstrated the ability to slow anatomical progression of GA lesions in clinical trials, these treatments have not yet shown clear benefits in functional vision outcomes — the aspects of vision most directly relevant to daily living. This discrepancy raises an important question: how do patients with GA perceive the acceptability of these invasive therapies, especially when significant vision improvement is uncertain?
A recent UK-based cross-sectional study aimed to explore this question by evaluating patients’ willingness to consider IVCI treatment when presented with the prospect of vision benefits. This article unpacks the findings and examines what they reveal about patient perspectives and the future of GA management.
The Science Behind Geographic Atrophy and Complement Inhibition
Geographic atrophy results from the gradual loss of retinal pigment epithelium cells and photoreceptors, key components essential for clear vision. Over time, these changes cause blind spots and substantial central vision impairment.
Complement system dysregulation, part of the body’s innate immune defense, has been implicated in GA’s pathogenesis. Excessive activation can damage retinal tissues. Complement inhibitors, delivered via injections directly into the eye, aim to modulate this harmful immune response and thereby slow lesion growth.
Multiple phase 3 clinical trials of IVCI therapies have successfully shown a deceleration in GA lesion progression, offering hope. However, these trials did not demonstrate significant improvements in secondary functional vision endpoints, such as visual acuity or contrast sensitivity. This discordance raises questions about the clinical meaningfulness of these anatomical findings to patients.
Exploring Patient Acceptability: The UK Multicenter Study
Between April 2023 and April 2024, researchers from nine geographically dispersed National Health Service (NHS) centers in the UK conducted a study involving 153 patients diagnosed with treatment-naive GA affecting at least one eye. Participants had a mean age of 82 years, and 60% were women; 38% had GA involving the central retina (fovea). The median visual acuity ranged roughly between 20/40 and 20/63 depending on the eye.
Participants were provided a patient-friendly information leaflet co-created with individuals who have lived experience of GA. This resource explained the treatment’s risks and benefits under the assumption that IVCI could deliver functional vision improvements. Afterward, participants completed a validated questionnaire assessing their acceptability of the therapy and a quality-of-life measure known as the EuroQol 5-dimension (EQ-5D) with an additional vision-specific module.
Key Findings: Acceptance Hinges on Perceived Effectiveness and Logistics
Over half (53%) of participants indicated that IVCI therapy would be “very much” or “extremely” acceptable under the hypothetical scenario that it improves vision outcomes. When including those who found the treatment moderately acceptable, the acceptability rose to 82%, a substantial majority.
Two important factors correlated strongly with acceptability: belief in the treatment’s effectiveness and confidence in the ability to regularly attend eye clinic appointments for injections. This finding underscores the dual importance of perceived benefit and treatment practicality.
These insights highlight that patient willingness to receive regular, invasive eye injections is not merely about the treatment’s biological effects. It also involves patients’ daily life considerations such as mobility, support systems, and trust in therapeutic value.
Why Functional Benefits Matter to Patients
Despite IVCIs slowing lesion progression anatomically, current therapies have not demonstrated clear benefits in functional vision — the practical ability to see, read, and navigate daily environments better or longer.
Mrs. Helen Jacobs, a recently diagnosed GA patient in London, eloquently expressed this concern: “I want treatments that truly help me see better or at least hold on to my sight. Slowing down the damage sounds good, but I need to know I’ll notice the difference in my life.”
This patient perspective aligns with the study’s findings: patients prioritize treatments they believe will improve or preserve functional vision. Without evidence of such benefits, adoption and adherence may wane despite anatomical progress.
Clinical Implications and Future Directions
The study’s results have several important implications for clinicians, researchers, and healthcare policymakers:
1. Patient Communication: Clear, transparent discussion about the expected benefits and limitations of therapies is essential. Patients must understand both anatomical and functional outcomes to make informed choices.
2. Clinical Trial Design: Future trials should prioritize and validate functional vision endpoints that resonate with patients, capturing quality-of-life improvements alongside lesion size changes.
3. Personalized Treatment Planning: Assessing a patient’s ability to attend frequent clinic visits and their beliefs about potential effectiveness can help tailor treatment approaches.
4. Support Services: Providing logistical support such as transport and appointment reminders could enhance treatment adherence and patient acceptance.
5. Continued Research: Ongoing investigation into combination therapies or new agents that can deliver both anatomical and functional benefits will satisfy the pivotal patient-centered goal.
Conclusion
The recent UK study reveals that a majority of patients with geographic atrophy would find intravitreal complement inhibitor therapy acceptable if meaningful vision improvements were assured. Patients’ belief in treatment efficacy and confidence in attending regular injections strongly influenced acceptability.
While current IVCIs do not yet provide demonstrated functional vision gains, these findings emphasize the critical importance of aligning drug development and clinical practice with patient priorities. Functional benefits that improve or preserve daily vision remain the gold standard therapy goal for GA.
As research advances, the voices and preferences of patients with GA must remain central to shaping care strategies, clinical trial endpoints, and healthcare policies — ensuring innovations deliver tangible, valued benefits to those affected by this challenging degenerative eye disease.
References
Dinah C, Enoch J, Ghulakhszian A, Sekhon M, Salvatore S, DeSalvo G, Kumar P, Banerjee S, Nayak D, Amoaku W, Shiew M, Osoba O, Crabb DP, Taylor DJ. Patient-Reported Importance of Functional Benefit in Geographic Atrophy. JAMA Ophthalmol. 2025 Sep 25:e253264. doi: 10.1001/jamaophthalmol.2025.3264. Epub ahead of print. PMID: 40996733; PMCID: PMC12464851.
