Loss Of Acuity Research Articles

How I do it - endoscopic endonasal optic nerve decompression for traumatic optic nerve neuropathy.

Traumatic optic neuropathy (TON) consists of damage to the optic nerve following head injury and affects about 0.5-5% of patients with closed head injuries. It is characterized by a sudden decrease in visual acuity and/or visual field loss. Surgical treatment is usually warranted when ongoing compression occurs at the level of the optic canal. We describe the technical nuances of endoscopic endonasal approach for compressive TON and add evidence supporting this approach as a valid option to treat this condition.

Overcoming Barriers: Diagnosis of High-Grade Melanoma: Perspective from a Clinical Case

We present the case of a 30-year-old male patient with loss of visual acuity in the left eye. The imaging study detected a lesion of high suspicion of tumor in the left eye. Enucleation of the left eye was performed, confirming the diagnosis of choroidal melanoma by histopathological study. Subsequently, the disease progressed with neoplastic activity in the lungs, liver, lymph nodes and central nervous system. A case description is provided along with a bibliographic review, focusing on the approach and prognostic factors in patients with metastatic disease.

Were there any missing mediators between visual impairment and anxiety symptoms? Results from Chinese Longitudinal Healthy Longevity Survey.

Visual impairment, encompassing low visual acuity and visual field loss, significantly impacts the older adult population worldwide, leading to increased disability and mortality risks. Recent studies suggest a strong association between visual impairment and anxiety, particularly among older adults. This study aims to explore the relationship between visual impairment and anxiety symptoms in older adult individuals in China, and to investigate potential mediating factors. Data for this study were derived from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), including 11,702 participants aged 65 and older. Visual impairment was assessed through self-reported visual function, while anxiety symptoms were measured using the 7-item Generalized Anxiety Disorder scale (GAD-7). Additional assessments included sleep quality and duration, exercise status, and dietary diversity. Logistic regression models and mediation analysis were employed to explore associations and mediating effects. The findings indicate that visual impairment is significantly associated with increased anxiety symptoms among the older adult (OR = 1.51, 95% CI: 1.32-1.72, p < 0.001). Mediation analysis revealed that sleep quality, dietary diversity score (DDS), and plant-based DDS significantly mediated the relationship between visual impairment and anxiety. In contrast, sleep duration, exercise, and animal-based DDS did not show significant mediating effects. Visual impairment is a crucial predictor of anxiety symptoms in the older adult. Improving sleep quality and promoting a diverse plant-based diet may mitigate anxiety symptoms in this population. Interventions targeting these areas could enhance the mental health and quality of life of older adult individuals with visual impairment.

Un caso de exoftalmos progresivo en una niña de 5 años

Introduction: spindle cell sarcoma is a rare tumor, with little presentation in the literature. Soft tissue tumors constitute a heterogeneous group, requiring a multidisciplinary approach. Clinical case: 5-year-old schoolboy who goes to his pediatrician for exophthalmos. His mother refers a progressive proptosis in the left eye of 6 months of evolution. No loss of visual acuity, in the last weeks intermittent pain with eye movements. On examination proptosis of the left eye with intermittent tearing and vascular lesion in the temporal portion of the same eye, he presented restriction of left eye movements. He was referred to the hospital emergency department where a head CT scan (Figure 1,2) was performed, revealing a unilateral left retroorbital lesion measuring 28 x 14 mm, causing proptosis, mass effect on retroocular structures and loss of ocular sphericity. Given the findings in the imaging tests, it was decided surgical intervention by means of frontotemporal craniotomy, subsequently receiving complementary treatment with local radiotherapy. Due to negative molecular pathology studies, the result was finally interpreted as undifferentiated 'adult-type' spindle cell sarcoma. Conclusion: although undifferentiated spindle cell sarcoma is a rare pathology, it should be included in the differential diagnosis of retro-orbital pathologies. The objective of this case is to review the main characteristics of spindle cell sarcoma, given its rapid and aggressive form of presentation, in a rare tumor.

Evaluation of refractive surgery with posterior chamber intraocular lenses in patients with high myopia treated in an Ophthalmologic Center of the city of Rosario, years 2019-2022

Introduction: Myopia is an ametropia that is highly prevalent and causes loss of visual acuity, characterized by having diopters greater than -5.00. The implantation of a posterior chamber intraocular lens represents a treatment option for those patients who cannot undergo the Excimer Laser technique.Objective: To describe the results achieved with the placement of posterior chamber intraocular lenses in patients with high myopia treated in an ophthalmologic center in the city of Rosario between the years of 2019-2022.Materials and Methods: Quantitative, descriptive, observational, retrospective, retrospective, cross-sectional, non-probabilistic study by convenience. Conducted at Centro Oftalmología Global, a private center specialized in ocular pathologies, located at Bv. Oroño 1003 in the city of Rosario - Santa Fe. Data were collected by review of medical records. The data obtained were entered into a Microsoft Excel database. The data were tabulated for presentation and analysis. Summary measures of central tendency (arithmetic mean, median and mode) and dispersion (standard deviation) and descriptive statistical techniques (frequency distributions, averages and percentages) were used.Results: A total of 38 medical records were studied, of which n=23 (60.5%) were female and n=15 (39.5%) were male. The mean age was 31.2 (SD ±2.84 years; min. 24 and max. 35). The age group with the highest frequency was 30 and 35 with 25 patients (65.8%). Of the total, n=21 (55.3%) were patients with high myopia and n=17 (45.7%) with high myopia and astigmatism. Of n=38, 44.7% presented preoperative visual acuity less than 1/10 and 26.3% of 1/10. Refractometry showed results between -3.00 to -20.00 diopters of sphere and -1.00 to -6.00 diopters of cylinder.Conclusion: It was possible to assess that 86.8% of the patients who underwent refractive surgery were able to achieve an optimal visual quality (10/10) after LCI placement, and of the total number of patients (n=38) studied, only 5 (13.2%) presented complications in the postoperative period

Risk factors for early and late retinal detachment after boston type I keratoprosthesis surgery.

To determine the differential risk factors for retinal detachment (RD) after Boston Type 1 Keratoprosthesis (B1KPro) during the first year after surgery (early RD; ERD) and afterwards (late RD; LRD). Retrospective cohort study of 94 eyes (90 patients) undergoing B1KPro implantation at Centro de Oftalmología Barraquer from June 2006 to July 2022 with a minimum follow-up of one year. The incidence of RD in the whole sample after B1KPro implantation was 29% (27/94), occurring in 21% of eyes (ERD; 20/94) the first year, and in 7% afterwards (LRD; 7/94). Hypotony was revealed as a significant risk factor for ERD (16/19 = 84%; OR = 14.5, P < 0.0001), together with aphakia (16/20 = 80%; OR = 5.9, P = 0.004), intraocular lens (IOL) removal (4/8 = 50%; OR = 6.2, P = 0.03), previous choroidal detachment (CD; 7/20 = 35%; OR = 35.5, P = 0.001) and previous pars plana vitrectomy (PPV; 15/20 = 75%; OR = 6.6, P = 0.006). Multivariate analysis included hypotony and PPV at any time as variables significantly associated with ERD occurrence. The occurrence of LRD was significantly related to peripheral retinal changes, detected few days before (4/6 = 66%; OR = 65, P < 0.0001). Hypotony emerged as one of the main factors influencing ERD occurrence after B1KPro implantation. Additionally, previous CD, PPV, aphakia, and IOL removal should be considered to estimate the risk of postoperative retinal detachment. In contrast, peripheral retinal changes after B1KPro seem to be significantly related to LRD occurrence. This study reinforces the need for frequent intraocular pressure evaluation, and comprehensive periodic retinal assessment over time. What is known Retinal detachment (RD) is a severe complication after Boston Type 1 Keratoprosthesis (B1KPro) implantation, resulting in a permanent reduction of visual acuity in a clinically relevant percentage of eyes. The time of RD occurrence after B1KPro implantation differs in the literature but is reported to be more common within the first year. Previous aphakia, choroidal detachment, or RD repair, intraocular lens removal, vitritis, or history of Nd-YAG laser have been described as risk factors for RD after B1KPro surgery in samples with varying follow-ups. Multivariate analysis in the first year after B1KPro surgery showed hypotony and pars plana vitrectomy at any time as significant risk factors for early RD. Late RD cases, occurring after one year following the B1KPro surgery, seem to be significantly related to peripheral retinal changes suffered a few days before loss of visual acuity and RD diagnosis. It is plausible to think that risk factors for RD after B1KPro differ in short and long postoperative times.

Gene Therapy for Achromatopsia.

Achromatopsia is the most common cone dysfunction syndrome, affecting 1 in 30,000 people. It is an autosomal recessive disorder with a heterogeneous genetic background with variants reported in CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6. Up to 90% of achromatopsia patients harbour mutations in CNGA3 or CNB3, which encode for the alpha and beta subunits of the cone cyclic nucleotide-gated (CNG) channel in cone-specific phototransduction. The condition presents at birth or early infancy with poor visual acuity, nystagmus, photophobia, and colour vision loss in all axes. Multimodal retinal imaging has provided insightful information to characterise achromatopsia patients based on their genotype. There is no FDA-approved treatment for achromatopsia; however, studies have reported several preclinical gene therapies with anatomical and functional improvements reported in vivo. There are currently five gene therapy clinical trials registered for human patients at the phase I/II stage and for CNGA3 or CNGB3 causing achromatopsia. This review aims to discuss the genetics of achromatopsia, genotypic and phenotypic correlations in multimodal retinal imaging, and the developments and challenges in gene therapy clinical trials.

Predictors of Permanent Vision Loss in Giant Cell Arteritis

ABSTRACT To report on the occurrence and characteristics of eye manifestations and determine the predictors of permanent vision loss (PVL) in patients with giant cell arteritis. Case-control study. Retrospective cohort study of 258 patients diagnosed with giant cell arteritis (GCA) over a 20- year period at a single institution. Eighty nine of 258 patients (34.5%) with GCA had vision symptoms and 56 (21.7%) developed PVL. Acute loss of vision with no preceding ocular symptoms occurred in 28.5%; for those with symptoms, median time to vision loss was 4.5 days. Bilateral clinical eye involvement was present in 38%, mostly anterior ischemic optic neuropathy (AION), rarely vascular occlusions. Vision loss was severe with acuity of count fingers or less or mean deficit −20 decibels or less in at least one eye in 80% of patients with PVL. Following initiation of GC treatment, 23% of patients continued to have further vision loss and only 5% showed improvement. We found predictors of PVL by multivariate analysis to be increased age (OR 1.05, p0.040), jaw claudication (OR 2.29, p = .040), diplopia (OR 2.74, p = .039), increased platelets (OR 2.98, p = .020) and lower CRP (OR 0.63, p = .004). We found there is a 27.3% decrease in the odds of having PVL when CRP value is doubled, keeping all other variables fixed. Permanent vision loss was 3.07 times more likely in the absence of polymyalgia rheumatica and 4.25 times more likely in patients without headaches. Ocular involvement in GCA is common, usually severe with little chance of recovery. Detailed analysis of visual acuity and visual field loss in our PVL cohort adds valuable data to the literature which lacks this information. Older patients with jaw claudication, diplopia, and increased platelets are at higher risk for permanent vision loss, especially when PMR and headache are absent and acute phase reactants lower.

Charles Bonnet Syndrome asssociated with glaucoma in a 95-year old female: A case report

Vision problems increase with age and evaluation of visual perception is important in geriatric practice. Visual hallucinations may occur in elderly individuals for various reasons. Hallucinations secondary to loss of severe visual acuity or visual field, also known as Charles Bonnet Syndrome(CBS), may be rarely seen. We reported a case of CBS secondary to glaucoma in a 95-year-old female patient. It is stated that this patient's visual hallucination has been developing for the last 3 years. The patient had simple hallucinations that were not related to dementia or psychotic disorder. The patient had accompanying depressive mood and fear of being alone. Visual hallucinations decreased after antidepressant treatment. The oldest known case of CBS is presented.

Pars-plana vitrectomy for the treatment of vitreous amyloid in patients with hereditary transthyretin amyloidosis.

To describe a series of patients with hereditary transthyretin amyloidosis (ATTRv) with vitreous amyloid and to study the efficacy and safety of pars plana vitrectomy (PPV) for its treatment. Retrospective study of 266 patients with ATTRv due to Val30Met mutation submitted to PPV for vitreous amyloid, with a minimum 3-month follow-up. Indications for surgery were disabling myodesopsia or 2 lines loss in visual acuity. Only the first operated eye was considered for analysis. Male patients were operated at younger age (51.0 vs 53.6, p<0.001). Best-corrected visual acuity improved from 0.38 to 0.89 (decimal scale, p<0.001). Preoperative glaucoma was associated with lower gain in visual acuity (p<0.001). During the follow-up, 69%, 22% and 1% developed new onset glaucoma, retinal angiopathy or retinal detachment, respectively, and 36% required cataract surgery. PPV was also required in the fellow eye in 57%. ATTRv-related death occurred in 27%, 9.3 95%CI 8.0-10.7 years after PPV. Vitreous opacities are frequently the first symptomatic manifestation of ocular amyloidosis. Moreover, they may be a marker of mortality. Vitrectomy is a safe and effective treatment, but these patients require long-term follow-up to monitor the development or worsening of glaucoma or retinal angiopathy.

The relationship between visual acuity loss and GABAergic inhibition in amblyopia

Abstract Early childhood experience alters visual development, a process exemplified by amblyopia, a common neurodevelopmental condition resulting in cortically reduced vision in one eye. Visual deficits in amblyopia may be a consequence of abnormal suppressive interactions in the primary visual cortex by inhibitory neurotransmitter γ-aminobutyric acid (GABA). We examined the relationship between visual acuity loss and GABA+ in adult human participants with amblyopia. Single-voxel proton magnetic resonance spectroscopy (MRS) data were collected from the early visual cortex (EVC) and posterior cingulate cortex (control region) of 28 male and female adults with current or past amblyopia while they viewed flashing checkerboards monocularly, binocularly, or while they had their eyes closed. First, we compared GABA+ concentrations between conditions to evaluate suppressive binocular interactions. Then, we correlated the degree of visual acuity loss with GABA+ levels to test whether GABAergic inhibition could explain visual acuity deficits. Visual cortex GABA+ was not modulated by viewing condition, and we found weak evidence for a negative correlation between visual acuity deficits and GABA+. These findings suggest that reduced vision in one eye due to amblyopia is not strongly linked to GABAergic inhibition in the visual cortex. We advanced our understanding of early experience dependent plasticity in the human brain by testing the association between visual acuity deficits and visual cortex GABA in amblyopes of the most common subtypes. Our study shows that the relationship was not as clear as expected and provides avenues for future investigation.

Effectiveness of a Structured Trauma Template in Improving Clinical Examination Accuracy in Maxillofacial Trauma: A Prospective Study

Study Design Prospective pre-post study. Objective Maxillofacial trauma presenting to the emergency department (ED) are often accompanied with complex concomitant injuries, thereby making thorough diagnosis and treatment plan quite an exacting task owing to the demanding conditions of the ED. The use of a structured maxillofacial trauma template helps in documenting the injuries comprehensively, aids in treatment planning, avoids medical negligence thereby improving the quality of care given to the patient. The study introduced a structured maxillofacial trauma template to improve the quality of the ED documentation. Methods A total of 220 patients were evaluated for the quality of their ED documentation from September 2023 till February 2024. The group A included 110 patients where complete medical documentation was done routinely on a blank A4 sized paper, group B included 110 patients where the documentation was done using the structured oral and maxillofacial trauma template. The ED notes were thoroughly evaluated by the 2 independent authors for record completeness and documentation rate of history and examination findings. Results The introduction of trauma template demonstrated a significant improvement of 18.95 % in record completeness. Significant improvement was seen in documentation rate among the covariates like place of injury, time of evaluation, primary care given, wound classification, dento-alveolar injury, ophthalmic evaluation, nerve injury evaluation, comorbidities with P = .001, and referral with P = .03. The ophthalmic evaluation showed significant improvement among covariates (loss of visual acuity, reflexes, diplopia, enophthalmos, subconjunctival haemorrhage, chemosis, periorbital oedema, periorbital ecchymosis, ocular dystopia) with P = .001, and extraocular muscle restriction with P = .004. Conclusions The study demonstrated that the use of a structured oral and maxillofacial trauma template can significantly improve the quality of the ED documentation and contributes to better patient care in the ED.

Ocular and Serum Profiles of Inflammatory Molecules Associated With Retinitis Pigmentosa.

To investigate the profiles and correlations between local and systemic inflammatory molecules in patients with retinitis pigmentosa (RP). The paired samples of aqueous humor and serum were collected from 36 eyes of 36 typical patients with RP and 25 eyes of age-matched patients with cataracts. The concentration of cytokines/chemokines was evaluated by a multiplexed immunoarray (Q-Plex). The correlations between ocular and serum inflammatory molecules and their association with visual function were analyzed. The aqueous levels of IL-6, Eotaxin, GROα, I-309, IL-8, IP-10, MCP-1, MCP-2, RANTES, and TARC were significantly elevated in patients with RP compared to controls (all P < 0.05). The detection rate of aqueous IL-23 was higher in patients with RP (27.8%) compared with controls (0%). In patients with RP, Spearman correlation test demonstrated positive correlations for IL-23, I-309, IL-8, and RANTES between aqueous and serum expression levels (IL-23: ⍴ = 0.8604, P < 0.0001; I-309: ρ = 0.4172, P = 0.0113; IL-8: ρ = 0.3325, P = 0.0476; RANTES: ρ = 0.6685, P < 0.0001). In addition, higher aqueous IL-23 was associated with faster visual acuity loss in 10 patients with RP with detected aqueous IL-23 (ρ = 0.4119 and P = 0.0264). Multiple factor analysis confirmed that aqueous and serum IL-23 were associated with visual acuity loss in patients with RP. These findings suggest that ocular and systemic inflammatory responses have a close interaction in patients with RP. Further longitudinal studies with larger cohorts are needed to explore the correlation between specific inflammatory pathways and the progression of RP. This study demonstrates the local-systemic interaction of immune responses in patients with RP.

The Discrepancy Between Visual Acuity Decline and Foveal Involvement in Geographic Atrophy

To investigate the discrepancy between visual acuity (VA) decline and foveal involvement in geographic atrophy (GA) secondary to non-exudative age-related macular degeneration (AMD), and to explore how early retinal changes impact the progression of visual impairment. Retrospective, longitudinal cohort study. This study evaluated 80 eyes from 60 patients (mean age 74.2±10 years) with progressing non-neovascular AMD using blue-light fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT). The study monitored the onset of foveal involvement and analyzed VA changes over an average follow-up of 60±26.4 months, encompassing 785 observations. Mixed-effects models with natural splines assessed the effects of demographic and ocular characteristics on baseline VA and its rate of decline. Survival analyses compared the timing of anatomical changes with the most rapid functional declines, indicated by the highest first derivative of VA trajectories. Discrepancies between visual and anatomical changes were explored using generalized linear mixed-effects models. VA declined consistently by an average of 0.010 LogMAR per month (SE: 0.0003, p<0.001). The onset of foveal involvement significantly exacerbated this decline, adding an average loss of 0.15 LogMAR (SE: 0.02, p<0.001). Stabilization of VA typically occurred around 41 months post-foveal involvement. Significant factors associated with worse baseline VA were older age, female gender, unifocal GA morphology, and drusen-associated forms of GA (p<0.05). The most rapid declines in VA typically occurred about 9 months (IQR 0-27 months) prior to detectable subfoveal changes. The reticular FAF pattern (27/46 [59%] vs. 2/13 [15%], p=0.02) and smaller baseline GA lesions (p=0.01) were associated with faster deterioration preceding visible foveal damage. This study demonstrates that significant VA loss in GA can precede detectable foveal involvement, suggesting a window for early interventions to slow the progression of visual impairment. Identifying specific GA characteristics and FAF patterns as predictors of rapid VA decline supports the need for personalized treatment strategies to optimize outcomes for patients with non-exudative AMD.

Metabolic Deficits in the Retina of a Familial Dysautonomia Mouse Model.

Neurodegenerative retinal diseases such as glaucoma, diabetic retinopathy, Leber's hereditary optic neuropathy (LHON), and dominant optic atrophy (DOA) are marked by progressive death of retinal ganglion cells (RGC). This decline is promoted by structural and functional mitochondrial deficits, including electron transport chain (ETC) impairments, increased oxidative stress, and reduced energy (ATP) production. These cellular mechanisms associated with progressive optic nerve atrophy have been similarly observed in familial dysautonomia (FD) patients, who experience gradual loss of visual acuity due to the degeneration of RGCs, which is thought to be caused by a breakdown of mitochondrial structures, and a disruption in ETC function. Retinal metabolism plays a crucial role in meeting the elevated energetic demands of this tissue, and recent characterizations of FD patients' serum and stool metabolomes have indicated alterations in central metabolic processes and potential systemic deficits of taurine, a small molecule essential for retina and overall eye health. The present study sought to elucidate metabolic alterations that contribute to the progressive degeneration of RGCs observed in FD. Additionally, a critical subpopulation of retinal interneurons, the dopaminergic amacrine cells, mediate the integration and modulation of visual information in a time-dependent manner to RGCs. As these cells have been associated with RGC loss in the neurodegenerative disease Parkinson's, which shares hallmarks with FD, a targeted analysis of the dopaminergic amacrine cells and their product, dopamine, was also undertaken. One dimensional (1D) proton (1H) nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and retinal histology methods were employed to characterize retinae from the retina-specific Elp1 conditional knockout (CKO) FD mouse model (Pax6-Cre; Elp1LoxP/LoxP). Metabolite alterations correlated temporally with progressive RGC degeneration and were associated with reduced mitochondrial function, alterations in ATP production through the Cahill and mini-Krebs cycles, and phospholipid metabolism. Dopaminergic amacrine cell populations were reduced at timepoints P30-P90, and dopamine levels were 25-35% lower in CKO retinae compared to control retinae at P60. Overall, this study has expanded upon our current understanding of retina pathology in FD. This knowledge may apply to other retinal diseases that share hallmark features with FD and may help guide new avenues for novel non-invasive therapeutics to mitigate the progressive optic neuropathy in FD.

A new, adaptive, self-administered, and generalizable method used to measure visual acuity.

Angular Indication Measurement (AIM) is an adaptive, self-administered, and generalizable orientation-judgment method designed to interrogate visual functions. We introduce AIM Visual Acuity (VA) and show its features and outcome measures. Angular Indication Measurement VA's ability to detect defocus was comparable with that of an Early Treatment of Diabetic Retinopathy Study (ETDRS) letter chart and showed greater sensitivity to astigmatic blur. This proof-of-concept study introduces Angular Indication Measurement and applies it to VA. First, we compared the ability of AIM-VA and ETDRS to detect defocus and astigmatic blur in 22 normally sighted adults. Spherical and cylindrical lenses in the dominant eye induced blur. Second, we compared repeatability over two tests of AIM-VA and ETDRS. A repeated-measure analysis of variance showed a main effect for defocus blur and test. For the astigmatism experiment, an interaction between blur and orientation was found. Pairwise comparisons showed that AIM was more sensitive to astigmatic-induced VA loss than ETDRS. Bland-Altman plots showed small bias and no systematic learning effect for either test type and improved repeatability with more than two adaptive steps for AIM-VA. Angular Indication Measurement VA's ability to detect defocus was comparable with that of an ETDRS letter chart and showed greater sensitivity to induced astigmatic blur, and AIM-VA's repeatability is comparable with ETDRS when using two or more adaptive steps. Angular Indication Measurement's self-administered orientation judgment approach is generalizable to interrogate other visual functions, e.g., contrast, color, motion, and stereovision.

Risk Factors for Amblyopia

Amblyopia is characterized by loss of visual acuity without visible organic cause, although it is attributed to abnormal brain development. It is prevalent in children from zero to 8 years, but there are cases of older patients and even adults. This article aims to systematize the main risk factors for amblyopia in studies carried out in ophthalmic care centers. For this purpose, a documentary review of academic and scientific material was carried out. Two risk factors were identified, ocular type such as strabismus, myopia, isolated or combined astigmatism, refractive errors, and non-ocular such as prematurity, low birth weight, and maternal smoking. Risk factors are genetic risk factors, failure to detect and treat early, due to socio-environmental factors like poverty and lack of ophthalmic services, or extraordinary situations such as the COVID-19 pandemic.

Aflibercept 8 mg/0.07 mL (Eylea HD)

CADTH recommends that aflibercept 8mg/ 0.07 mL (Eylea HD) be reimbursed by public drug plans for treating diabetic macular edema (DME) if certain conditions are met. Eylea HD should only be covered to treat adult patients with DME due to type 1 or 2 diabetes mellitus, with a central retinal thickness (CRT) of 300 µm or more (or 320 µm or more on the Spectralis scan) and a score of 78 to 24 letters in the eye with decreased vision primarily due to DME according to the early treatment diabetic retinopathy study (ETDRS) scoring system. Eylea HD should only be reimbursed if it is prescribed by an ophthalmologist with experience managing DME, it is used in combination with other antivascular endothelial growth factor (VEGF) drugs, and the cost of Eylea HD is not more than the least costly anti-VEGF drug covered by the public drug plans for the treatment of DME. Eylea HD should only be authorized for reimbursement for 12 months the first time it is used. Eylea HD should no longer be reimbursed if injections need to be given more frequently than every 12 weeks or if the patient experiences &gt; 10 letter loss in best-corrected visual acuity (BCVA) from week 12 in association with persistent or worsening DME and &gt; 50 μm increase in CRT from week 12.

Comparison of a Whole-Brain Contrast-Enhanced 3D TSE T1WI versus Orbits Contrast-Enhanced 2D Coronal T1WI at 3T MRI for the Detection of Optic Nerve Enhancement in Patients with Acute Loss of Visual Acuity.

MR imaging is the technique of choice for patients presenting with acute loss of visual acuity with no obvious ophthalmologic cause. The goal of our study was to compare orbits contrast-enhanced 2D coronal T1WI with a whole-brain contrast-enhanced 3D (WBCE-3D) TSE T1WI at 3T for the detection of optic nerve enhancement. This institutional review board-approved retrospective single-center study included patients presenting with acute loss of vision who underwent 3T MR imaging from November 2014 to February 2020. Two radiologists, blinded to all data, individually assessed the presence of enhancement of the optic nerve on orbits contrast-enhanced 2D T1WI and WBCE-3D T1WI separately and in random order. A McNemar test and a Cohen κ method were used for comparing the 2 MR imaging sequences. One thousand twenty-three patients (638 women and 385 men; mean age, 42 [SD, 18.3] years) were included. There was a strong concordance between WBCE-3D T1WI and orbits contrast-enhanced 2D T1WI when detecting enhancement of the optic nerve: κ = 0.87 (95% CI, 0.84-0.90). WBCE-3D T1WI was significantly more likely to detect canalicular enhancement compared with orbits contrast-enhanced 2D T1WI: 178/1023 (17.4%) versus 138/1023 (13.5%) (P < .001) and 108/1023 (10.6%) versus 90/1023 (8.8%) (P = .04), respectively. The WBCE-3D T1WI sequence detected 27/1023 (3%) instances of optic disc enhancement versus 0/1023 (0%) on orbits contrast-enhanced 2D T1WI. There were significantly fewer severe artifacts on WBCE-3D T1WI compared with orbits contrast-enhanced 2D T1WI: 68/1023 (6.6%) versus 101/1023 (9.8%) (P < .001). The median reader-reported confidence was significantly higher with coronal T1WI compared with 3D TSE T1WI: 5 (95% CI, 4-5) versus 3 (95% CI, 1-4; P < .001). Our study showed that there was a strong concordance between WBCE-3D T1WI and orbits contrast-enhanced 2D T1WI when detecting enhancement of the optic nerve in patients with acute loss of visual acuity with no obvious ophthalmologic cause. WBCE-3D T1WI demonstrated higher sensitivity and specificity in diagnosing optic neuritis, particularly in cases involving the canalicular segments.

Caspase-8-mediated inflammation but not apoptosis drives death of retinal ganglion cells and loss of visual function in glaucomaa.

Glaucoma is a complex multifactorial disease where apoptosis and inflammation represent two key pathogenic mechanisms. However, the relative contribution of apoptosis versus inflammation in axon degeneration and death of retinal ganglion cells (RGCs) is not well understood. In glaucoma, caspase-8 is linked to RGC apoptosis, as well as glial activation and neuroinflammation. To uncouple these two pathways and determine the extent to which caspase-8-mediated inflammation and/or apoptosis contributes to the death of RGCs, we used the caspase-8 D387A mutant mouse (Casp8 DA/DA ) in which a point mutation in the auto-cleavage site blocks caspase-8-mediated apoptosis but does not block caspase-8-mediated inflammation. Intracameral injection of magnetic microbeads was used to elevate the intraocular pressure (IOP) in wild-type, Fas deficient Faslpr, and Casp8 DA/DA mice. IOP was monitored by rebound tonometry. Two weeks post microbead injection, retinas were collected for microglia activation analysis. Five weeks post microbead injection, visual acuity and RGC function were assessed by optometer reflex (OMR) and pattern electroretinogram (pERG), respectively. Retina and optic nerves were processed for RGC and axon quantification. Two- and five-weeks post microbead injection, expression of the necrosis marker, RIPK3, was assessed by qPCR. Wild-type, Faslpr, and Casp8 DA/DA mice showed similar IOP elevation as compared to saline controls. A significant reduction in both visual acuity and pERG that correlated with a significant loss of RGCs and axons was observed in wild-type but not in Faslpr mice. The Casp8 DA/DA mice displayed a significant reduction in visual acuity and pERG amplitude and loss of RGCs and axons similar to that in wild-type mice. Immunostaining revealed equal numbers of activated microglia, double positive for P2ry12 and IB4, in the retinas from microbead-injected wild-type and Casp8 DA/DA mutant mice. qPCR analysis revealed no induction of RIPK3 in wild-type or Casp8 DA/DA mice at two- or five-weeks post microbead injection. Our results demonstrate that caspase-8-mediated extrinsic apoptosis is not involved in the death of RGCs in the microbead-induced mouse model of glaucoma implicating caspase-8-mediated inflammation, but not apoptosis, as the driving force in glaucoma progression. Taken together, these results identify the caspase-8-mediated inflammatory pathway as a potential target for neuroprotection in glaucoma.