In this week’s issue

• Avacincaptad pegol, a C5 inhibitor, has proved over its two year trial period that it is a safe and effective means of treating geographic atrophy.
• Hearing impairment is linked to poorer outcomes after vision rehabilitation, highlighting challenges of dual sensory loss.
• Immune checkpoint inhibitors may offer a protective role in early non-neovascular (dry) AMD. 
• Low-dose atropine may slow myopia progression, though treatment effects appear to be dependent on patient ethnicity.

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Ophthalmology

Avacincaptad pegol for geographic atrophy secondary to AMD

Is ACP still safe and effective for geographic atrophy after two years? Avacincaptad pegol (ACP), a pegylated RNA aptamer that inhibits C5, is an FDA-approved intravitreal injection used to slow the progression of geographic atrophy (GA) in age-related macular degeneration (AMD). ACP’s FDA approval in 2023 was based on one-year data from the GATHER1 and GATHER2 studies, which studied monthly injections of 2 mg of ACP versus control. This recent update presents new data from the two-year time point of the GATHER2 study, in which once monthly (EM) and every other month (EOM) injections of 2 mg ACP were compared to placebo. Over the two year trial period, the mean rate of GA area growth was 4.46 mm² with ACP EM and 5.18 mm² with sham, a difference in growth of 0.724 mm² (P = 0.0165), representing a 14% difference. The mean rate of GA area growth was 4.20 mm² with ACP EOM, a difference in growth of 0.976 mm² (nominal P = 0.0015) versus sham, representing a 19% difference. These results recapitulate the safety and efficacy of ACP in reducing growth of GA over two years, though the difference in efficacy between EM and EOM regimens raises questions that should be addressed in future studies.

JAMA Ophthalmology 

Impact of hearing impairment on vision rehabilitation in older adults

Does hearing impairment reduce gains from vision rehabilitation? Dual sensory impairment of vision and hearing is associated with an increased risk of cognitive impairment and significantly limits the ability to perform activities of daily living. Although common among older adults, limited research has examined the impact of hearing impairment on vision rehabilitation outcomes. Using data from the prospective Low Vision Rehabilitation Outcomes Study (LVROS), the authors evaluated whether vision rehabilitation achieved a minimum clinically important difference (MCID) in functional ability, as measured by the Activity Inventory. The study included 611 participants, of whom 358 reported normal hearing and 253 reported hearing impairment. Among the 407 participants with post-rehabilitation follow-up, 74 (31%) of those with normal hearing and 39 (23%) with hearing impairment achieved MCID. Participants with hearing impairment were less likely to achieve MCID compared to those with normal hearing (OR 0.58), independent of visual, cognitive, and psychological factors. These findings suggest that addressing hearing impairment may enhance the effectiveness of vision rehabilitation. Rehabilitation strategies should be adapted to incorporate hearing support, including assistive listening devices, the increased use of visual aids, written materials, and multimodal instruction for individuals with dual sensory impairment.

American Journal of Ophthalmology (AJO)

Immune checkpoint inhibitors and AMD: An unexpected association

Could cancer immunotherapy be quietly doing the retina a favor? Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults and has strong links to immune dysregulation, particularly involving T-cells. Immune checkpoint inhibitors (ICIs), which are widely used in cancer care, modulate T-cell activity and have been associated with systemic immune effects, including rare ocular events. Understanding whether ICIs influence AMD risk is clinically relevant as a growing number of older patients receive these therapies. This retrospective, propensity score-matched cohort study used TriNetX data to compare 5-year AMD incidence in adults ≥60 years with cancer treated with ICIs versus those not treated with ICIs. The study involved 36,037 matched patients per group. ICI-treated patients had a significantly lower risk of developing non-neovascular (dry) AMD over 5 years, particularly in early and intermediate stages (HR 0.77). No significant association was found between ICI use and neovascular (wet) AMD. These findings suggest that immune modulation of T-cell mediated pathways may be protective in early AMD and warrant further investigation.

British Journal of Ophthalmology

Low-dose atropine effective for myopia in children of all ethnicities?

When it comes to myopia, a patient's ethnicity might affect treatment efficacy. Atropine has become a popular therapy for pediatric myopia due to its minimal side effects and good tolerance. However, its actual clinical efficacy remains debated and data comparing efficacy across different ethnicities is limited. This meta-analysis evaluated 25 randomized clinical trials encompassing 4,374 myopic children to compare 0.01% atropine against a placebo. Researchers utilized the ratio of means to account for natural disease progression and assessed efficacy across different ethnicities. While 0.01% atropine reduced annual spherical equivalent refraction progression by 37% overall, there was a difference between different ethnicities. South Asian children experienced a 66% reduction in progression, whereas East Asian and white children saw reductions of 35% and 28%, respectively. Similar patterns emerged for axial length elongation. These results suggest that, while 0.01% atropine remains an effective control measure, providers should consider a patient's ethnicity and natural myopia trajectory when adjusting dosages and optimizing individual treatment strategies.

Ophthalmology Retina

Risk factors for endophthalmitis after first anti-VEGF injection

Who is at risk for post anti-VEGF injection endophthalmitis? Post-injection endophthalmitis is a rare but devastating complication of intravitreal anti-VEGF injections. This retrospective study used the IRIS Registry to identify risk factors for endophthalmitis following a patient’s first anti-VEGF injection. Over 600 cases were identified between 2016-2023. A prior history of intravitreal corticosteroid injections (OR 2.35) was associated with increased risk. People who had never smoked were associated with decreased risk (OR 0.71). There was no significant association with race, ethnicity, or insurance status. Patients with diabetic retinopathy presented with endophthalmitis earlier than patients with AMD (P=0.03). This study highlights demographic factors that may increase risk for endophthalmitis, highlighting the importance of risk management as anti-VEGF injections steadily increase.

Digital Medicine

Analysis of approved deep learning for diabetic retinopathy detection

Diabetic retinopathy (DR) remains a leading cause of preventable blindness worldwide, affecting an estimated 100 million people, with early screening essential to preserving vision. While several AI-based screening tools have now received regulatory clearance, evidence on their real-world diagnostic accuracy has until now been fragmented across diverse populations, imaging protocols, and clinical settings, making it difficult to draw confident conclusions about system-level performance. This systematic review and meta-analysis aggregated 82 evaluation datasets of regulator-approved deep learning systems for DR screening, spanning studies conducted between 2016 and 2025 across 30 countries including cleared systems such as IDx-DR, EyeArt, and RetCAD. The pooled per-patient sensitivity was 93% and specificity 90%, closely paralleling expert clinical grading. Per-eye analysis yielded similarly strong results at 92% sensitivity and 93% specificity. Importantly, performance remained robust across geographically and ethnically diverse populations, suggesting that these tools generalize well beyond the datasets on which they were originally trained. These findings reinforce the viability of approved AI systems as reliable frontline DR screening tools. With the global burden of diabetes continuing to rise, scalable, validated AI screening could meaningfully reduce vision loss by enabling earlier detection and timely referral, particularly in primary care and resource-limited settings where specialist access remains a barrier. 

Ranibizumab vs. Verteporfin PDT for neovascular AMD (ANCHOR)

Anchors aweigh! Say farewell to verteporfin and ahoy to ranibizumab. In this double-masked phase III clinical trial, ranibizumab, an anti-VEGF antibody, was compared with the standard of care of the time - verteporfin photodynamic therapy (PDT). 423 patients with age-related macular degeneration (AMD) with predominantly classic neovascularization (CNV) were randomized to receive either verteporfin PDT, or monthly intravitreal ranibizumab (0.3 mg or 0.5 mg) for 2 years.

Key Points

• Ranibizumab was superior in preserving and improving visual acuity: ~90% lost fewer than 15 letters, and 34-41% gained >15 letters compared to ~65% and 6.3% in the PDT group
• Ranibizumab treatment significantly improved the size and severity of angiographic lesions, stabilizing the total lesion area and decreasing area of classic CNV
• Ranibizumab did not increase risk of ocular or systemic adverse events

Results of the ANCHOR trial confirmed the clinical benefit of ranibizumab found in the landmark MARINA study, and demonstrated that ranibizumab outperformed verteporfin PDT in all measures evaluated in AMD patients with predominantly classical CNV lesions. Together they were instrumental in altering clinical practice and providing new hope in patients with numerous retinal conditions