Search Results (44)

Non-arteritic anterior ischemic optic neuropathy (NAION) leads to retinal ganglion cell (RGC) loss and visual impairment, with no effective treatment. This study investigated the neuroprotective effect of 670 nm photobiomodulation (PBM) in a rat NAION model (rNAION). Wistar rats received 670 nm light exposure (10-min, 3000 lux) twice daily for 3 days after rAION injury, followed by 4 days of light treatment once a day. This study evaluated the neuroprotective effects of 670 nm light in an rNAION model. Rats received 670 nm light therapy (10 min/day, 3000 lux) for seven days post-injury. Treatment improved visual function (a 3.36-fold increase in FVEP amplitude), enhanced RGC survival (1.55-fold), and reduced apoptosis (a 15.86-fold reduction in TUNEL-positive cells). Inflammatory cytokines and ED1+ macrophage infiltration were significantly decreased. Oxidative stress was attenuated, with increased ATP, Nrf2, and PGC-1α levels and improved mitochondrial dynamics. These findings support 670 nm light as a potential therapy for NAION. Full article

Mitochondria are vital organelles responsible for ATP production and metabolic regulation, essential for energy-intensive cells such as retinal ganglion cells. Dysfunction in mitochondrial oxidative phosphorylation or mitochondrial DNA (mtDNA) pathogenic variants can disrupt ATP synthesis, cause oxidative stress, and lead to cell death. This has profound implications for tissues such as the retina, optic nerve, and retinal pigment epithelium, which are dependent on robust mitochondrial function. In this review, we provide a comprehensive compilation of pathogenic variants in the mtDNA associated with various ophthalmic diseases, including Leber’s hereditary optic neuropathy, chronic progressive external ophthalmoplegia, Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, among others. We highlight the genetic variants implicated in these conditions, their pathogenic roles, and the phenotypic consequences of mitochondrial dysfunction in ocular tissues. In addition to well-established mutations, we also discuss the emerging evidence of the role of mtDNA’s variants in complex multifactorial diseases, such as non-arteritic anterior ischemic optic neuropathy, primary open-angle glaucoma, and age-related macular degeneration. The review aims to serve as a valuable resource for clinicians and researchers, providing a detailed overview of mtDNA pathogenic variants and their clinical significance in the context of mitochondrial-related eye diseases. Full article

Nonarteritic anterior ischemic optic neuropathy (NAION) is an ischemic lesion of the anterior optic nerve (ON), currently untreatable due to the length of time from symptom onset until treatment. We evaluated angiotensin-(1-7) (Ang-(1-7)): the MAS1-receptor ligand, as a possible NAION treatment using the rodent NAION model (rNAION). Long-Evans rats were unilaterally rNAION-induced. One-day post-induction, lesion severity was quantified via optic nerve head (ONH) edema using spectral domain optical coherence tomography. Animals meeting rNAION induction criteria were randomized into (1) Subcutaneous Ang-(1-7) infusion for 28 days and (2) Vehicle. Visual function was assessed using both visual acuity and flash visual evoked potentials (fVEP). Tissues were collected >30d and RGC neurons were quantified by stereology. ONs were histologically examined for inflammation. Ang-(1-7) improved post-rNAION visual function. Ang-(1-7)-treated animals showed improved visual acuity (ANCOVA: p = 0.0084) and improved fVEP amplitudes (ANCOVA: p = 0.0378) vs vehicle controls. The relative degree of improvement correlated with ONH edema severity. Treated animals showed trends towards increased RGC survival, and reduced optic nerve inflammatory cell infiltration. Ang-(1-7) is the first agent effective ≥1 day after rNAION induction. Ang-(1-7) type agonists may be useful in improving long-term function and neuronal survival in clinical NAION and other forms of white matter ischemia. Full article

The treatment of arteritic anterior ischemic optic neuropathy (AAION), non-arteritic ischemic optic neuropathy (NAAION), and posterior ischemic optic neuropathy (PION) is a topic of ongoing research with mixed evidence on some pharmacotherapies and a need for more consensus. This manuscript provides an overview of these conditions’ current, potential future, and attempted pharmacotherapies. AAION’s current treatment regimen consists of high-dose steroids, with methotrexate, tocilizumab, and abatacept, being the most viable steroid-sparing therapy candidates. As for NAAION, the treatments being tried are vast, with mixed evidence supporting each modality. Similarly, despite the various treatment options explored, there still needs to be a universally effective therapy for PION. More research is needed to formulate an agreed-upon treatment regimen for these conditions. Full article

Purpose: While patients with cardiovascular comorbidities are at a higher risk for the occurrence of non-arteritic anterior ischemic optic neuropathy (NAION), it is unclear whether adherence to medication results in risk reduction. The purpose of this study was to investigate whether nonadherence to medical therapy for cardiovascular morbidity correlates with a higher risk for NAION when compared to patients with strict adherence. Methods: A retrospective case-control study was conducted among members of Clalit Health Services in Israel from 2001 to 2022. For each of the 757 NAION cases, three controls (totaling 2271 patients) were matched based on birth year and sex, with a propensity score analysis employed to adjust for a range of comorbidities. A patient was deemed nonadherent with medical treatment if their purchased quantity of medication was less than 60% of the prescribed annual dosage. Mixed models were used to evaluate exposure differences, and conditional logistic regression was applied, incorporating adjustments for socioeconomic status and ethnicity, to examine the impact of medication nonadherence on NAION risk. Results: A total of 3028 patients were included in the study; 757 patients with the diagnosis of NAION and 2271 in the matched control group. The average age of NAION patients was 69 ± 9 years and 55% were male. After adjustments for socioeconomic status and ethnicity, nonadherence to calcium channel blockers (CCBs) (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.03–1.71) and anti-arrhythmic (OR: 5.67, 95% CI: 1.89–21.2) medications emerged as significant risk factors. Similarly, nonadherence to cardioprotective medications (OR: 1.46, 95% CI: 1.23–1.74) was also identified as a significant risk factor. Conclusions: Nonadherence to treatments for cardiovascular disease, specifically to medications known to improve prognosis, is associated with a higher risk for NAION. Full article

Takayasu arteritis is a chronic inflammatory vasculitis with granulomatous panarteritis particularly impacting large vessels including the aorta and its branches, especially the subclavian arteries, with clinical manifestation dependent on the involved artery. Sequelae of the active disease vary, including stenosis, occlusions, or aneurysmal dilatations of the large vessels. The prevalence of Takayasu arteritis is higher in the Asian population and in Japan, but quite low in the United States, varying from 0.9–8.4 per million people. Ocular manifestations are rare and lead to a delay in diagnosis and appropriate treatment. Ocular manifestations include Takayasu retinopathy, anterior ischemic optic neuropathy (AION), retinal artery occlusion (RAO) and retinal vein occlusion (RVO). We present two cases in which central retinal artery occlusion (CRAO) was associated with Takayasu arteritis. CRAO is an ophthalmic emergency with an incidence of 1.9 per 100,000 person years in the United States; only 5% of cases are arteritic, which can be observed with inflammatory vasculitides secondary to the formation of immune deposits. Full article

Background: To evaluate and review the current evidence regarding the association between ischemic optic neuropathy (ION) and internal carotid artery dissection (ICAD). Methods: We systematically reviewed studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA), searching three databases (Scopus, Pubmed, and Embase) for relevant articles that clearly described the correlation between ION and ICAD. All studies that examined the association between ICAD and the development of ION were synthesized. Quality assessment using the Newcastle–Ottawa Scale (NOS) and Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports and Case Series were conducted. Results: Our search yielded 198 manuscripts published in the English language. Following study screening, fourteen studies were selected. The number of participants with ION following ICAD ranged from one to four, with sixteen patients experiencing either anterior ION, posterior ION, or a combination of both. The anterior or posterior ischemic optic neuropathy (AION and PION) patients’ ages were 48.75 ± 11.75 and 49.62 ± 12.85, respectively. Fourteen out of sixteen patients experienced spontaneous ICAD, whereas the traumatic etiology was ascertained in two patients. Conclusions: Hence, albeit rare, ophthalmologists should consider ICAD a potential cause of ION, especially in young adults with concomitant cephalic pain and vision reduction. Full article

Aim: As a medical condition, pregnancy mandates the simultaneous treatment of both the mother and the fetus, making it a distinctive aspect of clinical medicine. Material and Method: We analyze the physiological changes occurring in the eyes and brain during pregnancy, as well as the neuro-ophthalmological manifestations that can occur during pregnancy. Studies published in both English and other languages, case reports, and reviews from 2011 to 2023 onwards were included. All surveys were acquired by exploring the databases. Results: We found a total of 2135 articles that showcase neuro-ophthalmic changes related to pregnancy: review and research articles (Science Direct 804, Web of Science 923, Scopus 345, and 63 Pub Med). In total, 86 studies were examined after applying the inclusion and exclusion criteria. Bilateral papilledema can be a warning sign for intracranial hypertension or cerebral venous sinus thrombosis. Additionally, when unilateral, it is important to differentially diagnose anterior ischemic optic neuropathy secondary to a hypercoagulant, compressive or inflammatory optic neuropathy, optic neuritis, or even orbital pseudotumor state. Severe eclampsia and preeclampsia can manifest as choroidal infarction, serous retinal detachment, and even cortical blindness. There can also be implications at the level of cranial nerves or transient Horner syndrome. Conclusions: Evaluating and treating a pregnant woman with neuro-ophthalmological manifestations is challenging. The obstetrician closely follows and has a medical relationship with the pregnant woman; hence he/she might be the first to be informed about the general condition of the pregnant woman or might request an ophthalmologic examination tailored to each specific case. Full article

The purpose of this study was to determine if worse visual acuity is associated with an increased risk of incident fall or mortality, independent of other relevant cofounders. This was a single-center retrospective cohort study of 428 new cases of anterior ischemic optic neuropathy (AION). Separate Cox proportional hazards models were constructed to evaluate the relationship between either logMAR visual acuity (VA) or legal blindness (20/200 or worse VA) and survival time to (1) encounter for fall, (2) mortality, and (3) a composite adverse outcome. Multivariable models were adjusted for a priori confounders. In adjusted models, a 1-unit increase in logMAR VA was associated with a significantly greater risk of an incident fall (adjusted HR 1.36, 95% CI (1.06–1.73), p = 0.014) and of mortality (adjusted HR 1.44, 95% CI (1.15–1.82), p = 0.002). Meeting criteria for legal blindness was also significantly associated with a higher risk of incident fall (HR 1.80, 95% CI (1.05–3.07), p = 0.032) and mortality (adjusted HR 2.16, 95% CI (1.29–3.63), p = 0.004). Among patients with AION, worse visual acuity or legal blindness conferred a significantly increased risk of falls and mortality, independent of coexistent comorbidities. Future studies should consider fall reduction interventions for patients with poor vision from severe eye disease such as AION. Full article

We evaluated whether inhibiting sterile alpha and (Toll/interleukin receptor (TIR)) motif-containing 1 (SARM1) activity protects retinal ganglion cells (RGCs) following ischemic axonopathy (rodent nonarteritic anterior ischemic optic neuropathy: rNAION) by itself and combined with ciliary neurotrophic factor (CNTF). Genetically modified SARM1(−) rats were rNAION-induced in one eye and compared against equivalently induced wild-type animals of the same background. Optic nerve (ON) diameters were quantified using optical coherence tomography (SD-OCT). RGCs were quantified 30 d post-induction using retinal stereology for Brn3a(+) nuclei. ON sections were analyzed by TEM and immunohistochemistry. SARM1(−)(−) and WT animals were then bilaterally sequentially rNAION-induced. One eye received intravitreal vehicle injection following induction; the contralateral side received CNTF and was analyzed 30 d post-induction. Inhibiting SARM1 activity suppressed axonal collapse following ischemic axonopathy. SARM1(−) animals significantly reduced RGC loss, compared with WT animals (49.4 ± 6.8% RGC loss in SARM1(−) vs. 63.6 ± 3.2% sem RGC loss in WT; Mann–Whitney one-tailed U-test, (p = 0.049)). IVT-CNTF treatment vs. IVT-vehicle in SARM1(−) animals further reduced RGC loss by 24% at 30 d post-induction, but CNTF did not, by itself, improve long-term RGC survival in WT animals compared with vehicle (Mann–Whitney one-tailed t-test; p = 0.033). While inhibiting SARM1 activity is itself neuroprotective, combining SARM1 inhibition and CNTF treatment generated a long-term, synergistic neuroprotective effect in ischemic neuropathy. Combinatorial treatments for NAION utilizing independent neuroprotective mechanisms may thus provide a greater effect than individual treatment modalities. Full article

Non-arteritic anterior ischemic optic neuropathy (NA-AION) represents one of the most important causes of blindness or severely impaired vision in middle-aged and elderly people. Unilateral optic disc edema and abrupt, painless vision loss are its defining features. It is commonly assumed that NA-AION is caused by an ischemic infarction of the optic nerve head, and, although the exact pathogenesis is still unknown, several risk factors and comorbidities associated with its development have been found. NA-AION occurs generally in patients older than 50 years who have small optic discs and vasculopathy risk factors. Even though numerous treatment options have been proposed, no available effective medical or surgical therapy or prophylactic measure for NA-AION currently exists. The purpose of present-day therapeutic strategies is therefore to identify and possibly control any underlying modifiable risk factors, aiming to prevent the development of new NA-AION episodes in the affected and fellow eye. A thorough assessment of NAION, including its history, epidemiology, etiology, pathophysiology, risk factors, associated comorbidities, clinical findings, diagnostic tests, treatment choices, prognosis, and future research, is the goal of this work. Full article

Geographic atrophy (GA) affects around 5 million individuals worldwide. Genome-wide, histopathologic, in vitro and animal studies have implicated the activation of the complement system and chronic local inflammation in the pathogenesis of GA. Recently, clinical trials have demonstrated that an intravitreal injection of pegcetacoplan, a C3 inhibitor, and avacincaptad pegol, a C5 inhibitor, both statistically significantly reduce the growth of GA up to 20% in a dose-dependent fashion. Furthermore, the protective effect of both pegcetacoplan and avacincaptad appear to increase with time. However, despite these anatomic outcomes, visual function has not improved as these drugs appear to only slow down the degenerative process. Unexpected adverse events included conversion to exudative NV-AMD with both drugs. Occlusive retinal vasculitis and anterior ischemic optic neuropathy have been reported in pegcetacoplan-treated eyes. Full article

Purpose: This study aimed to investigate whether intravitreal aflibercept was safe and effective in patients with acute nonarteritic anterior ischemic optic neuropathy (NAION). Methods: This was a chart study of 25 individuals with acute NAION (25 eyes). An intravitreal injection of 2 mg/0.05 mL of aflibercept was administered to fifteen participants. The remaining ten patients in the control group were given standard care. The researchers measured the initial visual acuity, retinal nerve fiber layer thickness (RNFLT), and automated perimetry. During the follow-up period, the researchers measured the final visual acuity, RNFLT, automated perimetry, and side effects. Results: Visual acuity and visual field assessment were significantly improved in the study group, and optical coherence tomography testing demonstrated significant disc edema resolution. The therapy results differed significantly between the two groups regarding visual outcomes (F = 0.027, p = 0.039) and RNFLT decrease (F = 5.507, p = 0.003). However, the difference in visual field alterations was not significant (F = 0.724, p = 0.387). Conclusions: Intravitreal injection of aflibercept can significantly improve visual acuity and resolve disc edema in patients with acute NAION. Intravitreal aflibercept may be an alternative treatment for acute NAION. However, a large series investigation is needed to assess the long-term therapeutic benefit and safety of intravitreal aflibercept in patients with acute NAION. Full article

Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, an imbalance in the redox status characterized by an excess of reactive oxygen species (ROS), in driving cell death through apoptosis, autophagy, and inflammation. This review provides an overview of ROS-related processes underlying four extensively studied optic nerve diseases: glaucoma, Leber’s hereditary optic neuropathy (LHON), anterior ischemic optic neuropathy (AION), and optic neuritis (ON). Furthermore, we present preclinical findings on antioxidants, with the objective of evaluating the potential therapeutic benefits of targeting oxidative stress in the treatment of optic neuropathies. Full article

The global pandemic impact of the COVID-19 infection included clinical manifestations that affected several organs and systems, with various neuro-ophthalmological manifestations associated with the infection. These are rare and occur either secondary to the presence of the virus or by an autoimmune mechanism secondary to viral antigens. The manifestations are atypical, being present even in the absence of the systemic symptoms typical of a SARS-CoV-2 infection. In this article, we introduce a series of three clinical cases with neuro-ophthalmological manifestations associated with COVID infection that were shown in Ophthalmology Clinic of St. Spiridon Emergency Hospital. Case 1 is that of a 45-year-old male patient with no personal history of general pathology or ophthalmology, with binocular diplopia, painful red eyes, and lacrimal hypersecretion with a sudden onset of about 4 days. Based on the evaluations, a positive diagnosis of orbital cellulitis in both eyes is made. Case 2 is that of a 52-year-old female patient with general PPA (personal pathological antecedents) of SARS-CoV-2 infection 1 month prior to presentation with decreased visual acuity in the right eye and a positive central scotoma, preceded by photopsia and vertigo with balance disorders. The diagnosis is made at the right eye for retrobulbar optic neuritis and post-SARS-CoV-2 infection status. The last clinical case is that of a 55-year-old male patient known to have high blood pressure (HBP) with a sudden, painless decrease in VARE approximately 3 weeks post-SARS-CoV-2 immunization (Pfizer vaccine first dose). The diagnosis is made after consulting all the RE results for central retinal vein thrombosis. Conclusions: Although the cases were quickly and efficiently investigated and the treatment was administered adequately by a multidisciplinary team (cases 1 and 3), the evolution was not favorable in all three situations. Atypical neuro-ophthalmological manifestations can also be present in the absence of systemic symptoms typical of SARS-CoV-2 infection. Full article