Audio link: 

https://open.spotify.com/episode/2qzQXzcOdUUfz4N6Bf3sjI?si=eAaqyucbSSS_GNCU1a_OcA

In this week’s issue

• Ocular inflammation (along with female sex and treatment interruptions) was a significant risk factor for developing anti-Adalimumab antibodies, which happened in approximately 1/5th of patients on treatment with Adalimumab.
• Thinning of the ganglion cell layer/inner plexiform layer and outer retinal layers in children with type 1 diabetes was associated with higher A1c values.
• A review of MRSA keratitis found high multidrug resistance (85.7% of cases), but all were susceptible to vancomycin. On average, vision did not improve after treatment, and many required procedural or surgical intervention. 
• Keratoconus patients have significantly higher levels of oxidative stress biomarkers, and activation with sulforaphane (an antioxidant) decreased stress-induced cell death in diseased corneal stromal tissues.

Ophthalmology

Does ocular inflammation increase the risk of anti-Adalimumab antibody development?

Not every patient responds to biologic therapy the same way. Adalimumab, a TNF-α inhibitor, is widely used to treat autoimmune diseases and has demonstrated significant efficacy in the management of noninfectious uveitis. However, some patients develop anti-Adalimumab antibodies (AAA), which can reduce treatment effectiveness. Although previous studies have identified several risk factors for AAA development, such as the absence of concomitant immunosuppression and female sex, the relationship between AAA and ocular inflammation remains unclear. In this retrospective study, investigators analyzed data from 704 patients receiving Adalimumab for various autoimmune diseases to determine whether ocular inflammation is associated with the development of AAA. AAAs developed in 21.5% of patients during follow-up. Female sex, treatment interruptions, and ocular inflammation were independent risk factors for antibody formation. Patients who had ocular inflammation developed antibodies significantly earlier than those without ocular involvement. These findings support therapeutic drug monitoring and consistent treatment adherence, particularly for patients with ocular inflammation and female patients, to help minimize immunogenicity and optimize long-term treatment outcomes.

JAMA Ophthalmology 

Is retinal layer thickness associated with worse glycemic outcomes and diabetic retinopathy in youth with type 1 diabetes?

Read between the layers! Studies show that up to 52% of children with type 1 diabetes (T1DM) have diabetic retinopathy (DR), which can lead to vision loss. New evidence shows that retinal thinning is associated with the early stages of DR and may appear before any observable micro- or macroscopic vascular changes. A prospective cohort study examined 294 youth (578 eyes) with T1DM and assessed the thickness of 3 neuroretinal layers: retinal nerve fiber layer (RNFL), ganglion cell and inner plexiform layer (GCL+IPL), and the GCL+IPL+RNFL. Thinner GCL+IPL and outer retinal layers were associated with higher hemoglobin A1c. There was no correlation between the thickness of any layer and the presence or absence of DR. These results indicate that tracking retinal changes in children with T1DM could serve as an early biomarker of diabetic health.

American Journal of Ophthalmology 

MRSA keratitis in the era of multidrug resistance: Clinical outcomes and genomic insights

Susceptible on paper, devastating in practice. Methicillin-resistant Staphylococcus aureus (MRSA) keratitis is a fulminant corneal infection with guarded visual prognosis. The mec gene, carried on a mobile genetic element, mediates resistance in MRSA. It encodes a penicillin-binding protein with low affinity for beta-lactam antibiotics, thereby complicating treatment of these infections. This multicenter retrospective case series analyzed clinical outcomes and genomic epidemiology in 70 eyes with culture-proven MRSA-keratitis. Visual acuity did not significantly improve following treatment, and the median post-treatment BCVA was LogMAR 2.30, indicating severe visual impairment. Seventeen cases (24.3%) required either procedural or surgical intervention. Multidrug resistance (>3 antibiotic classes) was present in 85.7% of isolates, yet all cases were susceptible to vancomycin. In addition, there was low susceptibility to fluoroquinolones, which are commonly used for empirical monotherapy. Interestingly, the majority of isolates belonged to CC5 MRSA strains, a lineage of MRSA associated with difficult-to-treat hospital-acquired infection. These findings support the continued use of fortified vancomycin as first-line therapy but highlight poor visual outcomes and high rates of multidrug resistance, underscoring the need for improved treatment strategies and ongoing antimicrobial surveillance.

Investigative Ophthalmology & Visual Science

Can antioxidant therapy change the future of keratoconus?

Turns out, corneas don’t handle stress very well either. Keratoconus is a progressive corneal disease characterized by thinning and steepening that leads to irregular astigmatism and vision loss. Although treatments such as corneal collagen cross-linking can slow disease progression, there is no definitive cure. Previous studies suggest unresolved oxidative stress and impaired antioxidant defenses may contribute to keratoconus. Researchers examined donor corneal stromal cells with tear fluid analysis from 57 patients with keratoconus and 34 controls to investigate oxidative stress, antioxidant signaling, and the effects of sulforaphane, a naturally occurring antioxidant compound. Compared with healthy controls, keratoconus patients had significantly higher tear levels of oxidative stress biomarkers. Activation of the NRF2 antioxidant pathway with sulforaphane restored antioxidant signaling and reduced oxidative stress-induced cell death in diseased corneal stromal cells. Tear biomarker levels also correlated with increasing corneal steepness, suggesting oxidative stress may contribute to disease severity. These findings suggest that impaired antioxidant defenses may contribute to keratoconus progression and identify oxidative stress as a promising target for future therapies.

Journal of Glaucoma

Less medication, stable IOP: Long-term outcomes of phaco-MIGS in NTG

Managing normal-tension glaucoma is challenging. Minimally invasive glaucoma surgery (MIGS) techniques have gained popularity for their safety profiles and rapid postoperative recovery, but current research on the long-term outcomes of Phaco-Hydrus in normal-tension glaucoma (NTG) patients remains limited. This is a retrospective study of 77 NTG eyes from Singapore (Tan Tock Seng Hospital) and Canada (University of Montreal) that received Phaco-Hydrus between December 2014 and May 2023, with follow-up through post-operative month 36. Although no significant difference in intraocular pressure was observed over the study period, the proportion of medication-free eyes increased from 7.8% at baseline to 45.2% at post-operative month 36, with an adjusted mean difference of -0.7 ± 0.2. Overall, these findings indicate that Phaco-Hydrus could significantly decrease medication use in NTG patients, though the results are limited by low follow-up rates. 

Ophthalmology Science

Partly cloudy with a chance of pressure spikes

Can AI predict intraocular pressure fluctuations in patients with open-angle glaucoma? Elevated intraocular pressure (IOP) is a key risk factor for glaucoma progression, making IOP monitoring essential for preventing vision loss. This study was based on ARGOS-SC01, a prospective multi-center clinical trial that enrolled 24 glaucoma patients implanted with EyeMate-SC, a suprachoroidal telemetric IOP sensor. The device enabled high-frequency, continuous IOP monitoring over nearly 3 years. The authors investigated short-term (7, 14, and 28 days) predictors of long-term fluctuations (273 and 364 days), finding weak correlations (Pearson r ≤ 0.33). Out of 1224 Random Forest Classifier models developed, the top 5 achieved Area Under the Receiver Operating Characteristic (AUROC) 0.81–0.86, accuracy of 0.72–0.81, sensitivity of 0.72–0.78, and specificity of 0.70–0.82. Features of these models included short-term fluctuation, ocular pulse amplitude, age, BMI, and central corneal thickness. The mean 24-hour IOP was the most significant feature, contributing 35-55% to model performance, while short-term fluctuations contributed less than 10%. These results suggest that long-term IOP fluctuations can be predicted using machine learning when clinical and demographic features are combined with IOP data, but short-term fluctuations alone are insufficient. 

Supplemental Therapeutic Oxygen for Prethreshold ROP

They say that oxygen is the most valuable resource on earth, but can you give more O2 to decrease the rates of retinopathy of prematurity progression? In the 2000 STOP-ROP study, patients with prethreshold retinopathy of prematurity (ROP) were randomized to treatment with conventional O2 goals of 89-94% (n = 325) and supplemental O2 goals of 96-99% (n = 324) for at least two weeks until both eyes were at study endpoints.

Key Points

• Increasing O2 goals did not decrease rates of progression to confirmed threshold ROP compared to conventional O2 goals
• Patients receiving supplemental O2 therapy were more likely to have worse pulmonary outcomes and longer hospitalization times

Overall, the STOP-ROP study is a landmark study because it showed that increasing O2 goals was not associated with the prevention of worsening ROP and, actually, could lead to worse outcomes in this population.