Current Issue

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In this week’s issue:

• Inhibitory transcranial direct current stimulation of the visual cortex significantly reduces frequency of visual hallucinations in Charles Bonnet Syndrome.
• A large meta-analysis finds that patients with age-related macular degeneration, specifically non-exudative, are at increased risk of developing Alzheimer’s disease.
• Macular ganglion cell complex thinning in glaucoma is associated with central visual field defects, suggesting that OCT Macula imaging could be used in decision making in glaucoma.

Ophthalmology

Transcranial direct current stimulation reduces visual hallucinations in Charles Bonnet Syndrome

Seeking a new treatment option? Charles Bonnet Syndrome (CBS) is a term used to describe vivid hallucinations people experience after significant vision loss in the absence of psychiatric or cognitive illness. Although there is minimal physical risk in CBS, affected people experience reduced quality of life and independence. Current pharmacologic intervention includes anticonvulsants or antipsychotics, but the literature suggests there is little to no benefit. In this study, researchers determined whether inhibitory transcranial direct current stimulation (tDCS) of the visual cortex can remediate visual hallucinations in CBS. 16 participants were enrolled in this randomized, placebo-controlled study, where they received 4 days of either active or placebo treatment; after 4 weeks, participants underwent the converse treatment. Active inhibitory stimulation of the visual cortex resulted in a significant reduction in the frequency of visual hallucinations compared to placebo, especially for individuals who had higher occipital excitability on EEG assessment prior to stimulation. Additionally, tDCS therapy was not associated with any adverse effects. This study is the first to assess the use of tDCS in CBS treatment and its positive results warrant larger-scale clinical trials to further characterize its efficacy.  

JAMA Ophthalmology

The influence of ganglion cell complex thinning on central visual field loss

Can these gangs of cells really mess with your vision? Macular ganglion cell complex (GCC) thinning is a feature of glaucoma, and it is unclear how the rate of thinning impacts visual field loss over a patient’s clinical course. In this retrospective cohort study, 202 eyes from 139 glaucoma patients during 2014 to 2019 were analyzed for rates of macula GCC thinning via OCT macula testing and central visual field loss via HVF 10-2 testing. The results showed 163 eyes (80.7%) were slow OCT progressors with a GCC thinning rate of −0.3 μm/y (95% CI, −0.4 to −0.2 μm/y) and 39 (19.3%) were fast OCT progressors with a thinning rate of −1.6 μm/y (−1.8 to −1.3 μm/y). The rates of 10-2 visual field mean deviation worsening among slow and fast OCT progressors were −0.10 dB/y (95% CI, −0.16 to 0.00 dB/y) and −0.34 dB/y (95% CI, −0.51 to −0.16 dB/y), respectively (difference, −0.26; P = .008). Rapid macular thinning was associated with faster central visual field decline, which supports the practice of using macular OCT to aid in clinical decisions and therapy considerations. 

American Journal of Ophthalmology

A fateful friendship: AMD associated with Alzheimer’s disease

The eyes are the window into the… brain. Dementia, and more specifically Alzheimer’s disease (AD), is an important cause of disability in the elderly worldwide, while age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is believed to have many clinical and pathological similarities to AD. For example, an increase of certain noncoding RNAs have been found both in the macula of the AMD patient and in the superior temporal lobe neocortex of the AD patient. Researchers sought to confirm this association between the two diseases. This systemic review and meta-analysis included studies examining the association of AMD with AD. In total, 8,223,581 patients were included across the studies. Results demonstrated that patients with AMD were at a 1.22-fold risk for dementia and 1.21-fold risk for AD compared with non-AMD patients. Further, patients with non-exudative AMD had a significant association with AD (pooled HR, 1.21), while patients with exudative AMD did not exhibit a significant association with AD. This study confirms an increased risk for dementia or AD among those with AMD. The commonly shared pathways in the two diseases could explain the association. All in all, this study should inspire the ophthalmologist to offer AMD patients an awareness of the possible comorbidity of AD.

IOVS

What role does AMPK/MFF play in dry eye pathogenesis?

The mitochondria is the powerhouse of the eye! Tear hypertonicity, a core mechanism in the development of dry eye, is implicated in reactive oxygen species (ROS) generation and resultant mitochondrial damage. This study explores the role of adenosine monophosphate-activated protein kinase (AMPK)/Mitochondrial fission factor (MFF) in the development of dry eye via mitochondrial integrity pathways. Human corneal epithelial cells (HCECs) were exposed to high osmotic pressure and mice were dosed with scopolamine to induce and simulate dry eye pathology. Both in vivo and in vitro models demonstrated extensive mitochondrial fission and mitophagy, and RNA and protein studies showed an increase in expression of proteins in the AMPK/MFF pathway. Lentiviral knockdown of MFF reversed the molecular findings in HCECs and was protective against ROS and cell death. This study concludes that in dry eye, mitochondrial dynamics favor fragmentation and autophagic clearance, processes which are regulated by the AMPK/MFF pathway. Thus, this pathway could be a promising target for future dry eye therapeutics.

JAMA Ophthalmology 

Putting the diversity back in data collection

DNA isn’t the only thing in need of mismatch repair. Diabetic macular edema (DME) and retinal vein occlusion (RVO) represent ocular conditions leading to blindness that disproportionately affect minority populations. This study sought to identify racial and ethnic over- and underrepresentation in randomized control trials (RTCs) for DME and RVO. In this retrospective cross-sectional analysis, racial and ethnic demographic data of US-based RCTs for DME and RVO from 2004 – 2020 were compared to 2010 US Census data. Of the 23 included RCTs, 22 represented a demographic distribution that was significantly different from the 2010 census data. Hispanic study participants were most regularly underrepresented, while white study participants were most regularly overrepresented. Further efforts to recruit and retain underrepresented populations in RCTs are needed to improve the external validity of potentially sight saving studies.  

Cryotherapy for ROP (CRYO-ROP)

Colder than the tip of the eyesburg. The multicenter Trial of Cryotherapy for Retinopathy of Prematurity was developed in the 1980s to provide a more evidence-based approach to the treatment of retinopathy of prematurity. More specifically, the study sought to determine the value and outcomes of peripheral ablative treatment (specifically cryotherapy) for the treatment of ROP.

Key Points

• Treated eyes had a 49.3% reduction in “unfavorable” outcomes based on masked grading of fundus photographs at 3 and 12 months (21.8% in treated, 43.0% in untreated)
• In the 10 year follow-up, it was noted that anatomic outcomes were better than functional outcomes, meaning outcomes based on imaging may overestimate the impact of treatment

Overall, the CRYO-ROP was a landmark study for both the screening and treatment of ROP, even if the specific treatment has become a secondary one in the time since. The main findings of this study showcase a decreased incidence of blindness and retinal detachment, improved visual acuity outcomes, and improved structural outcomes in eyes treated with cryotherapy. A second-generation study, the ET-ROP, studied laser photocoagulation as ablative treatment, which has now become the paradigm for ROP management.

A 45 year-old man reports experiencing episodic eye pain with disturbance of vision, notably after exercising at the gym. Slit lamp biomicroscopy revealed:       

All can be present in this patient’s condition except:

A. Myopia 

B. Increased C/D ratio

C. Narrow angle on gonioscopy

D. Peripheral concave iris  

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