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April 10, 2024


The most important ophthalmology research updates, delivered directly to you.
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In this week's issue
  • Phase II trial for LHON found no significant changes in BCVA after topical elamipretide, post-hoc analysis showed improvements in central visual field.
  • Single-nucleotide and rare coding variants in over 30 genes were associated with primary angle-closure (PAC) disease.
  • Higher IOP variability and range is associated with faster rate of GCS thinning, suggesting that IOP variations may independently cause macular changes.
  • Higher levels of saccharin were found in well-controlled AMD patients compared to those with chronically active choroidal neovascularization (CNV).

Elamipretide, a topical solution for treatment of LHON? 

Ophthalmology

Could elamipretide, a topical solution, be the key solution for Leber Hereditary Optic Neuropathy? Leber Hereditary Optic Neuropathy (LHON), the most common hereditary optic neuropathy, is inherited mitochondrially and causes subacute severe vision loss. Elamipretide, a tetrapeptide known for stabilizing the mitochondrial electron transport chain and decreasing ROS byproducts, has been investigated in the treatment of other mitochondrial-associated conditions. This study assesses the safety and efficacy of elamipretide topical ophthalmic solution. This phase 2, single-center double-masked randomized clinical trial administered 1% topical elamipretide solution in the left eye, right eye, or both eyes of 12 patients affected by m.11778G>A LHON over 52 weeks. There was not a significant difference in the change in BCVA from baseline in elamipretide-treated eyes at any time point (P=0.9891). The post-hoc analysis showed change from baseline in the central visual field was significantly greater in elamipretide-treated eyes when averaged over all time points (P < 0.0001). Although this study did not meet its BCVA endpoints, the post-hoc analysis of visual field changes warrants further investigation into the potential of elamipretide solution as treatment for LHON.

I dream of gene(ies): An analysis of genetic correlations in primary angle-closure

JAMA Ophthalmology

Those look like skinny “genes” from this angle… Primary angle-closure glaucoma affected ~17.14 million individuals in 2020 and is projected to reach 35 million by 2040, with older age, female sex, ethnicity, and genetic factors as major risk factors. This 2-staged systematic review and meta-analysis examines the effects of genetic variants, including common single-nucleotide variants (SNVs) and rare coding variants, on primary angle-closure (PAC) disease, including subtypes of PAC glaucoma, PAC, and PAC suspect. Of the 69 studies eligible for meta-analysis, 17 SNVs in 15 genes/loci showed an association with PAC disease while 15 SNVs in 13 genes/loci showed associations with PAC glaucoma. Stratification analysis revealed different PAC disease-associated genes among ethnic populations, highlighting the incredible genetic complexity of primary angle-closure disease, even across ethnicities. Further research of the genotype-phenotype correlation with pathway analyses could lead to better understanding of individual susceptibility.

Long-term IOP variability and ganglion complex thinning in glaucoma

American Journal of Ophthalmology

Under pressure! Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma. Despite treatment, many patients with normal IOP ranges (10-21 mmHg) still have vision loss. Long-term IOP variability leading to stress fluctuations can damage retinal tissue. Macular optical coherence tomography (OCT) is essential for diagnosing central retinal ganglion cell changes, which can happen earlier than functional changes in some glaucoma patients. Using OCT to identify anatomical alterations can enable timely and effective intervention before actual visual loss occurs. This prospective cohort study evaluated the association of IOP’s mean and variability with the rate of ganglion cell complex (GCC) layer thinning over time in glaucoma patients. It included 369 eyes of 249 glaucoma patients (mean age of 68.2), with at least 4 visits and 2 years of follow-up of OCTs. In multivariable models, faster annual rate of GCC thinning was associated with higher IOP fluctuation (−0.17[ 95% CI,−0.23 to −0.11] μm per 1–mm Hg higher) or higher IOP range (−0.07[95% CI, −0.09 to −0.05] μm per 1–mm Hg higher). These findings suggest that IOP variability independently influences macular change in glaucoma patients, regardless of baseline severity and even after adjusting for mean IOP. Additional research is warranted to validate if IOP variability could serve for clinical decision-making as a therapeutic target.

Exploring a protective role of saccharin in neovascular AMD

IOVS

Saccharin, spice, and everything nice. Neovascular age-related macular degeneration (nAMD), a leading cause of vision loss in older people, is characterized by VEGF-mediated choroidal neovascularization (CNV). VEGF activity in other organ systems has been linked with artificial sweeteners. This study explored the association of artificial sweeteners, including saccharin, and nAMD. First, a cross-sectional study of 46 nAMD patients undergoing anti-VEGF therapy, were evaluated clinically. Their blood samples were analyzed for metabolomics by liquid chromatography-tandem mass spectrometry. Saccharin levels were significantly higher in AMD patients with well-controlled disease compared to those with chronically active CNV (P=0.004). Next, a laser-induced model of choroidal neovascularization was performed in mice either treated with 0.03% saccharine or normal drinking water. Mice were evaluated by fluorescence angiography and fundus imaging after 14 days, and tissues were collected for qPCR and immunohistochemistry. Saccharin-treated mice showed fewer and less severe choroidal bleeding sites, decreased fibrotic scar formation, and decreased monocyte inflammation into the damaged tissue area. This study indicates a potentially protective role of saccharin in nAMD disease management. Animal and cell models complement this result by generating hypothetical pathways of action of saccharin, including inflammation, fibrosis, and/or the VERGR1 signaling network, that need to be further investigated.

Glaucoma

Reading from smartphones may transiently increase intraocular pressure

Journal of Glaucoma

Printed text might be a relic of the past, but at least reading it isn’t raising your IOP like reading on a smartphone does! Studies have suggested that reading may lower intraocular pressure (IOP) via lens accommodation enhancing aqueous humor outflow; however, more recent studies have reported increases in IOP among healthy individuals with reading on computer screens and smartphones. This study compared the effect of reading on IOP using printed text and smartphones in 60 healthy volunteers and 22 patients with primary open-angle glaucoma (POAG). The authors found that both modalities increased IOP significantly above baseline at 10-, 20-, and 30-minute reading intervals. Reading with a smartphone produced a larger maximum rise in IOP (+2.00 mmHg) compared to reading from printed text (+0.78, P = 0.002) in healthy volunteers. Similarly, in POAG patients, a greater rise in IOP was observed with smartphones (+3.42 mmHg) compared to printed text (+2.21 mmHg, P = 0.021), but not at all time points. Nevertheless, after 20 minutes of reading with either modality, the IOP returned to baseline. This study, while the first to compare reading modalities directly in individual patients, was limited to a young (mean age = 31 years in healthy volunteers and 49 years in POAG patients), predominantly male population.

Lens Landmarks
Does age affect retinal drusen, pigmentary abnormalities, and overall macular degeneration? In the Beaver Dam Eye study, 4926 patients from age 43 to 68 were studied using stereoscopic color fundus photography to answer this question.

Key Points:
  • Data indicated that individuals 75 years of age or older commonly had signs of AMD
  • Identified features included large drusen, soft indistinct drusen, abnormal retinal pigmentation, exudative macular degeneration, and geographic atrophy
  • 95.5% of the population studied had at least one drusen in the macula of one of their eyes.
Overall, the Beaver Dam Eye study is a landmark trial because it demonstrated the association between AMD and age, and was one of the first large scale prevalence studies for the disease. This association was deemed a “substantial public health problem” that previously had not been realized.

Question of the Week
A 60 y/o M presents with epiphora, photophobia, erythema, and blurred vision OU for the past two weeks. History is notable for myelofibrosis which he was diagnosed with at 59 years old. He received allogeneic hematopoietic stem cell transplant five months ago. One month ago he began experiencing tightness in his legs but no pain. On ocular exam, VA is 20/60 OD and 20/50 OS. IOP is 12 mmHg OU. Slit lamp exam was notable for meibobian gland dysfunction and 2-3+ SPK OU. The remainder of the exam is normal.
What is the most likely diagnosis?

A. Sjogren's syndrome
B. Scleroderma
C. Graft Versus Host Disease
D. Rosacea
E. Steven Johnson Syndrome


 
Keep scrolling for answer or click here
 

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