Doheny Eye Institute

A 21-year-old male presented with chronic left-sided rhinosinusitis and was found to have a left frontal sinus mass on maxillofacial computed tomography (CT). The mass measured approximately 1.9 × 1.3 × 2.3 cm in size and was contiguous with the intrasinus septum and anterior table of the frontal sinus. Imaging features were consistent with osteoma. An endoscopic endonasal approach resulted in subtotal resection of the mass. Eleven months later, the patient underwent a combined left transorbital and endoscopic surgical resection with oculofacial plastic surgery and otolaryngology. The mass was resected in its entirety, and histopathology confirmed an osteoma. This is one of the few reports of a unilateral transorbital frontal sinus osteoma resection and highlights the utility of the transorbital approach for minimally invasive access to the far-lateral frontal sinus.

Synaptic failure predicts cognitive decline in Alzheimer’s disease (AD), yet its impact and molecular drivers in the human retina remain unclear. Leveraging the retina as an accessible central nervous system (CNS) proxy, we integrated spatially resolved histopathology of retinal cross-sections with ultrastructural, proteomic, and biochemical profiling across independent postmortem cohorts spanning normal cognition, mild cognitive impairment due to AD (MCI), and AD dementia. We uncover early, progressive degeneration of excitatory glutamatergic synapses, evidenced by losses of presynaptic vesicular glutamate transporter 1 (VGLUT1) and synaptophysin, and postsynaptic density protein 95 (PSD95) and N-methyl-D-aspartate receptor subunit 2A (NMDAR2A), accompanied by disruption of synaptic ultrastructure. Retinal synaptic loss tightly associates with local accumulation of amyloid-β 42 (Aβ42) and immature tau species, heightened oxidative stress, and upregulation of the Aβ-binding death receptor p75 neurotrophin receptor (p75NTR). Notably, the synapse-enriched deubiquitinase ubiquitin C-terminal hydrolase L1 (UCHL1) is profoundly dysregulated, correlates with synaptic integrity and cognition, and emerges as the strongest retinal predictor of Braak stage and cognitive status in multivariable machine-learning models. Together, these findings position retinal Aβ/p75NTR-mediated UCHL1 imbalance as a proteostasis–synapse mechanistic hub and candidate biomarker reflecting AD severity.

Leber’s Hereditary Optic Neuropathy (LHON) is a rare genetic condition and severe neurological disorder characterized by dysfunctional mitochondria under extreme oxidative stress, resulting in retinal ganglion cell death and subsequent rapid bilateral loss of central vision. The m.14484T>C mutation in the ND6 subunit of mitochondrial complex I is known for inducing LHON, and is a prevalent LHON-associated mutation, yet its mechanism of impairment at the molecular level is currently unresolved. In this study, we explore the biophysical underpinnings of this mutation and its role in LHON through disruption of human complex I function. We consider, using atomistic simulations, the differential thermodynamics and kinetics of coenzyme Q10 binding between the mutant and wild-type forms, altered dynamics of the complex upon mutation, and key interactions between coenzyme Q10 and complex I binding sites. The hydrogen bond network present near and within the coenzyme Q10 binding domain, along with proper hydration of E-channel residues that couple redox chemistry to proton pumping, is found to be critical for complex I stability and quinone binding, which the ND6-centered mutation disrupts.

Microglia are the resident macrophages of the central nervous system (CNS) that respond to tissue infection and injury. In addition to their role in inflammation, microglia play a developmental role in circuit refinement through synaptic pruning. However, the mechanisms of synaptic pruning in neuroinflammation and neurodegeneration remain unknown. In this protocol, we use a mouse retina explant model to study microglia dynamics ex vivo. To examine microglia motility and their interactions with postsynaptic proteins, we label synapses with AAV-PSD95-RFP and record timelapse videos of motile microglia colocalized with postsynaptic proteins using spinning disk confocal microscopy. We then create surface and spot reconstructions of microglia and PSD95 using image analysis software. Data such as microglia displacement length, process speed, and contact with postsynaptic puncta can then be extracted from these surfaces to understand microglia behavior both in homeostatic states and after neuronal injury. This protocol can be useful in examining the role of microglia in synaptic pruning in retinal neurodegenerative diseases.

Précis:This is a retrospective observational study investigating the congruity between numerical and clinical hypotony and the risk factors for clinical manifestations of hypotony after trabeculectomy.Purpose:To identify risk factors associated with clinically meaningful hypotony after trabeculectomy.Design:Retrospective cohort study.Methods:Patients who underwent trabeculectomy with mitomycin-C (MMC) were included. Clinical hypotony was defined as the presence (≥ 3 wk after surgery) of choroidal detachment, hypotony keratopathy, hypotony maculopathy, or shallow anterior chamber or the need for trabeculectomy revision to resolve the hypotony at any time after surgery. Numerical hypotony was defined as intraocular pressure (IOP) ≤5 mmHg in 2 or more consecutive visits, at least one of them ≥ 3 weeks after surgery. Baseline, intraoperative, and postoperative characteristics were evaluated as potential risk factors. Univariable and multivariable analyses were conducted to assess the association between each characteristic and the presence of clinical hypotony.Results:Nine hundred ninety-two eyes were included. Two hundred eighty-four eyes (28.6%) met the criteria for numerical hypotony, 222 of which (79.9%) did not show any clinical sequelae of hypotony. 99 eyes (10%) met our criteria for clinical hypotony, whereas 42 of them (42.4%) did not have numerical hypotony. The most frequent manifestation of hypotony was serous choroidal effusion (54 eyes, 5.4%) followed by shallow anterior chamber (28 eyes, 2.8%). Thirty-four eyes (3.4%) underwent trabeculectomy revision to treat the hypotony. Asian ethnicity mitigated against the development of clinical hypotony (OR: 0.29, CI: 0.10–0.72, P=0.015) and the requirement for suture lysis postoperatively was associated with a lower risk of clinical hypotony (OR: 0.49, CI: 0.29–0.81, P=0.006).Conclusions:A minority of eyes (20.1%) with numerical hypotony showed clinical manifestations of low IOP. Asian ethnicity and eyes that required suture lysis postoperatively tended to have less incidence of clinical sequelae of hypotony after trabeculectomy.

Cutaneous squamous cell carcinoma has a propensity for perineural invasion. Treating perineural spread has involved surgery and adjuvant chemoradiation, and more recently, immune checkpoint inhibitors. This study aims to evaluate motor and sensory functional outcomes in patients with cranial neuropathies from perineural spread of squamous cell carcinoma, particularly those undergoing immunotherapy. This was a multicenter case series and literature review. Eighteen patients with cranial neuropathies from perineural spread had a mean age of 72.5 ± 9.7 years. Cranial nerves V and VII were most often involved. Treatments included radiotherapy (8/18; 44.4%), chemotherapy (7/18; 38.9%), and/or immunotherapy (11/18; 61.1%), with many receiving a combination of modalities (8/18; 44.4%). Of those receiving immunotherapy, 72.7% (8/11) demonstrated at least partial clinical and/or radiologic tumor response. Among those with functional outcomes documented, half had improvement in sensory/motor nerve function following immunotherapy (4/8; 50%). A literature review identified 55 articles describing 449 patients total with cranial neuropathies from squamous cell carcinoma perineural spread. Combinations of surgery, chemotherapy, and/or radiotherapy were employed, with immunotherapy used in 16 patients. From 5 patients on immunotherapy with documented functional outcomes, all demonstrated at least some improvement. Immunotherapy plays an evolving role in managing advanced squamous cell carcinoma. Functional improvements in cranial neuropathy were demonstrated in 50% of patients receiving treatment with immunotherapy at a mean of 32.6 months of follow-up. This may hold important implications for the timing of surgical intervention, particularly in the case of cranial nerves V and VII palsies.

<title>Abstract</title> <bold>Purpose</bold> Intracameral moxifloxacin administered at the conclusion of cataract surgery reduces postoperative drop burden and infection risk but may cause injection-related discomfort, potentially affecting patient safety and satisfaction. This study evaluated whether an additional mid-procedure dose of intracameral lidocaine could reduce pain associated with moxifloxacin injection. <bold>Methods</bold> This prospective interventional study included 50 cataract surgery patients under monitored anesthesia care. The interventional group (n=25) received an additional intracameral dose of 1% preservative-free lidocaine during instrument exchange, while the control group (n=25) did not. All patients then received intracameral moxifloxacin at the end of surgery, reporting verbal 0-10 pain scores before and after injection. Pain-delta scores, representing pain responses to moxifloxacin, were compared between the two groups. Patient age, sex, midazolam dosage administered prior to surgery, pre-operative spherical equivalent, and total operative time, were evaluated as potential confounders or effect modifiers. <bold>Results</bold> Mean pain-delta scores were significantly lower in the interventional group compared with controls (0.46 vs 2.22), representing a 1.76-point or 79% reduction in pain (p=0.003). On multiple linear regression, mid-procedure lidocaine remained independently associated with a 1.67-point reduction in pain-delta scores (95% CI: −2.83 to −0.50; p=0.006) after adjustment for demographic and perioperative factors. <bold>Conclusions</bold> A mid-procedure dose of lidocaine significantly reduces pain with intracameral moxifloxacin injection, independent of patient and perioperative variables. This simple, convenient, and low-cost intervention improves patient comfort and facilitates broader adoption of intracameral antibiotic prophylaxis during cataract surgery.