Visual outcome of various dose of glucocorticoids treatment in nonarteritic anterior ischemic optic neuropathy- a retrospective analysis.

BACKGROUND AND PURPOSE: The objective of this investigation was to assess the therapeutic efficacy of distinct glucocorticoid therapy dosages in the management of acute nonarteritic anterior ischemic optic neuropathy (NAION). MATERIALS AND METHODS: This retrospective, unmasked, and non-randomized study included a total of 85 patients. The patients were categorized into four groups: Group 1 (control) consisted of 15 patients who did not receive glucocorticoids, Group 2 included 16 patients administered with oral prednisone at a dosage of 1 mg/kg/d for 14 days, Group 3 comprised 30 patients who received 250 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days, and Group 4 encompassed 24 patients who received 500 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days. The best-corrected visual acuity (BCVA) was assessed at baseline and the final follow-up (> 7 days post-treatment). The changes in visual acuity between baseline and the 7-14 day follow-up, as well as between baseline and the concluding appraisal, were employed as metrics for assessing the extent of visual enhancement. RESULTS: No significant differences were noted in the final visual outcomes or in the changes between final visual acuity and baseline across the four groups. In Group 1 (control), the best-corrected visual acuity (BCVA) remained unchanged during final follow-ups compared to baseline. Conversely, the intervention groups exhibited statistically significant enhancements in BCVA during final follow-up (p = 0.012, p = 0.03, and p = 0.009 for Group 2, Group 3, and Group 4, respectively) when compared to baseline. During the 7-14 day follow-up, there was a significant difference in the changes between baseline BCVA and follow-up BCVA across the groups (p = 0.035). Go a step further by Bonferroni correction for multiple comparisons, group 4 showed a greater change in vision compared with group1 (p = 0.045). CONCLUSION: Our study on acute nonarteritic anterior ischemic optic neuropathy (NAION) showed no significant final visual outcome differences. Nevertheless, Groups 2, 3, and 4 demonstrated improved best-corrected visual acuity (BCVA) during the final follow-up. Notably, a 500-unit dose of methylprednisolone resulted in short-term BCVA enhancement. This suggests potential consideration of 500 units of methylprednisolone for short-term NAION vision improvement, despite its limited long-term impact.

A Successfully Treated Case of Posterior Ischemic Optic Neuropathy That Developed during Antihypertensive Therapy for Hypertensive Emergency.

A 33-year-old woman developed hypertensive emergency (268/168 mmHg) with renal failure and hypertensive retinopathy. Four hours after the initiation of antihypertensive therapy with the continuous infusion of nicardipine, her blood pressure (BP) decreased to 168/84 mmHg; however, the patient developed blindness. She was diagnosed with posterior ischemic optic neuropathy (PION). Her BP was maintained at approximately 175/90 mmHg until her vision improved. Olmesartan was initiated on day 13, and her BP decreased to approximately 135/95 mmHg without the re-exacerbation of vision loss. Although the prognosis of PION is poor, its early diagnosis and gradual antihypertensive therapy may help preserve the patient's vision.

Protective effects of compound M01 on retinal ganglion cells in experimental anterior ischemic optic neuropathy by inhibiting TXNIP/NLRP3 inflammasome pathway.

Apoptotic death of retinal ganglion cells (RGCs) is a common pathologic feature in different types of optic neuropathy, including ischemic optic neuropathy and glaucoma, ultimately leading to irreversible visual function loss. Potent and effective protection against RGC death is determinative in developing a successful treatment for these optic neuropathies. This study evaluated the neuroprotective effect of a HECT domain-E3 ubiquitin ligase inhibitor, M01, on retinal ganglion cells after ischemic injury. Experimental anterior ischemic optic neuropathy (AION) was induced by photothrombotic occlusion of microvessels supplying optic nerve in rats. M01 was administered (100 mg/Kg and 200 mg/Kg) subcutaneously for three consecutive days after AION induction. Administration of M01 (100 mg/Kg) significantly increased RGC survival and preserved visual function after AION induction. The number of TUNEL-positive cells and ED1-positive cells was significantly decreased, and optic disc edema was reduced considerably after ischemic infarction with M01 treatment. Moreover, M01 effectively ameliorated optic nerve demyelination and enhanced M2 microglial polarization after AION induction. M01 enhanced the expression of nuclear factor erythroid 2-related factor (Nrf2); subsequently, downregulated Thioredoxin interacting protein (TXNIP) expression, inhibited NLR family pyrin domain containing 3 (NLRP3) activation, and further decreased inflammatory factors, interleukin (IL)-1ß and IL-6 in the retina after ischemic injury. These findings suggested that M01 has therapeutic potential by modulating Nrf2 and TXNIP/NLRP3 inflammasome pathways in the retina and optic nerve ischemic damage-related diseases.

Immune Checkpoint Inhibitors and Optic Neuropathy: A Systematic Review.

INTRODUCTION: Immune checkpoint inhibitors are a class of monoclonal antibodies that are used as a mainstay of immunotherapy for multiple solid organ malignancies. With the recent increase in popularity of these agents, immune-related adverse events including optic neuropathy are becoming more frequently reported. This review aims to explore the association between immune checkpoint inhibitors and optic neuropathy through analysis of incidence, clinical features, investigations, treatment, and patient outcomes. METHOD: A systematic search of the databases PubMed/MEDLINE, Embase, and CENTRAL was performed from inception to September 2022. Data collection and risk of bias analysis was subsequently conducted in accordance with the PRISMA guidelines. RESULTS: Eleven articles fulfilled the inclusion criteria. The results showed an increased incidence of optic neuropathy among patients receiving immune checkpoint inhibitor therapy compared to the general population. Presentation with painless reduced visual acuity and optic disc swelling was most common. Investigation findings were poorly documented. The only two patients who achieved full resolution of symptoms were treated with oral prednisolone. CONCLUSION: There is a strong association between immune checkpoint inhibitor therapy and development of optic neuropathy. Although it remains uncommon, the incidence of optic neuropathy in this population exceeds that of the general population. Future research is needed to further characterise the risk profiles of patients who are most likely to develop ICI-associated optic neuropathy, and treatment pathways for these patients.

The Controversy of Chronotherapy: Emerging Evidence regarding Bedtime Dosing of Antihypertensive Medications in Non-Arteritic Anterior Ischemic Optic Neuropathy.

"Blindness upon awakening" occurs in a significant proportion of patients with non-arteritic anterior ischemic optic neuropathy (NAION). This observation has led to a notion that nocturnal hypotension is a significant contributor and, perhaps, the final insult in a multifactorial process leading to the development of NAION, as has been proposed in other ischemic events like strokes, myocardial infarction, and ischemic rest pain. An extension of this concept has led to the recommendation that patients who have experienced NAION avoid taking blood pressure medications at bedtime. However, mounting evidence in the cardiology literature suggests that nocturnal hypertension is associated with increased risk of cardiovascular morbidity. In two prospective blood pressure monitoring studies in 1994 and 1999, Hayreh observed an extreme dipping pattern in nocturnal systolic blood pressure in NAION patients compared to reported normal values. Yet, two subsequent ambulatory blood pressure studies found either normal or non-dipping patterns in NAION patients. The majority of clinical trials published since 1976 that have studied nocturnal administration of antihypertensives have reported enhanced blood pressure control and reduced cardiovascular risk. Most notably, the large, prospective 2020 Hygia Chronotherapy Trial reported a statistically-significant beneficial effect of nocturnal antihypertensive dosing on cardiovascular outcomes and mortality. The controversy regarding nocturnal hypotension and NAION is of increasing relevance as there is new evidence to suggest a beneficial effect of nocturnal antihypertensive dosing in cardiovascular risk. This new information should prompt a re-evaluation of the relevant risk-to-benefit of reducing the risk of NAION on one hand, and the potential increase of cardiovascular risk on the other. Definitive resolution of this question would require a prospective, randomized control study with input from both cardiology and ophthalmology.

Treatment of nonarteritic anterior ischemic optic neuropathy with an endothelin antagonist: ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy)-a multicentre randomised controlled trial protocol.

BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAAION) is a major cause of blindness in individuals over 50 years of age, with no available effective treatment. The oral dual endothelin receptor antagonist, bosentan, increases retinal optic nerve head blood flow in healthy humans and glaucoma patients. The objective of this trial is to assess the efficacy of bosentan administered at the acute stage in improving outcomes in NAAION patients. METHODS: ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy) is a phase III, interventional, prospective, multicentre, placebo-controlled randomised double-blind clinical trial. The primary outcome is change in the visual field mean deviation (MD) at 3 months (Humphrey 30-2 SITA standard programme). Secondary outcomes include MD and visual acuity changes up to 24 months, changes in peripapillary retinal nerve fibre and macular ganglion cell layer thickness in the affected eye, as measured by optical coherence tomography, rate of NAAION bilateralisation at 2 years, and quality-of-life. Patients over 50 years of age presenting with typical NAAION of recent onset (less than 21 days) are randomly assigned to either 125 mg oral bosentan or placebo, twice a day, during 8 weeks. Besides visits during the treatment phase, patients attend follow-up visits at 2, 3, 6, 12 and 24 months. The inclusion of patients began in August 2015 at five French University hospital ophthalmology departments and two specialised ophthalmology centres. It is planned to include 86 patients in this trial. To date we have included 72 patients and 49 have completed the full follow-up process. DISCUSSION: An endothelin receptor antagonist is a potential approach to improving the anatomical and functional prognosis of patients with NAAION. This multicentre double-blind randomised controlled trial is an opportunity to assess (1) the effect of bosentan on the structure and function of the optic nerve in NAAION, at 3 months, (2) the effect of bosentan on the bilateralisation rate at 24 months and (3) the tolerance profile of bosentan in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02377271 . Registered on March 3, 2015.

Erythropoietin in Optic Neuropathies: Current Future Strategies for Optic Nerve Protection and Repair.

Erythropoietin (EPO) is known as a hormone for erythropoiesis in response to anemia and hypoxia. However, the effect of EPO is not only limited to hematopoietic tissue. Several studies have highlighted the neuroprotective function of EPO in extra-hematopoietic tissues, especially the retina. EPO could interact with its heterodimer receptor (EPOR/ßcR) to exert its anti-apoptosis, anti-inflammation and anti-oxidation effects in preventing retinal ganglion cells death through different intracellular signaling pathways. In this review, we summarized the available pre-clinical studies of EPO in treating glaucomatous optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy and traumatic optic neuropathy. In addition, we explore the future strategies of EPO for optic nerve protection and repair, including advances in EPO derivates, and EPO deliveries. These strategies will lead to a new chapter in the treatment of optic neuropathy.

Vision loss in giant cell arteritis: case-based review.

Prompt initiation of pulse glucocorticoid treatment is recommended in case of visual symptoms and suspected or proven giant cell arteritis (GCA). Pulse treatment in most cases prevents involvement of an initially unaffected fellow eye. We present the case of a biopsy-proven GCA in a 79-year-old man, complicated by sequential bilateral blindness. Initial unilateral vision loss was treated by 1 g methylprednisolone intravenously for 3 days, followed by 1 g/kg prednisone daily. Despite treatment, the second eye went completely blind 11 days after the initial vision loss. We performed a systematic search on Medline and Scopus aiming at identifying all cases of GCA complicated with loss of vision in a previously unaffected eye under pulse treatment for initially monocular vision loss. We identified 11 articles reporting 21 patients that met our inclusion criteria. Contralateral vision loss occurred 1-12 days following treatment initiation, with a median of 2 days. Treatment initiation was delayed up to 8 days since the initial vision loss, with a median delay of 2 days. Anterior ischemic optic neuropathy was the dominant mechanism of vision loss. Sequential involvement of the fellow eye in case of unilateral vision loss in GCA is rare. With 12-day interval being the longest reported, we conclude that even though the first 2 days are the most critical for the visual outcome, blindness in the initially unaffected eye may rarely occur later. Nonetheless, immediate initiation of pulse treatment remains of vital importance to preserve vision in the contralateral eye.

The Efficacy of Glucocorticoids in the Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis.

Background: To evaluate the clinical effects and safety of glucocorticoids for patients with nonarteritic anterior ischemic optic neuropathy (NAION). Methods: The databases MEDLINE, Embase, PubMed, Cochrane Database, and Web of Science were used to search for the relevant studies, and full-text articles that reported on the evaluation of glucocorticoids vs. no-treatment or placebo for patients with NAION. Review Manager 5.4 was used to estimate the pooled effects of the results among selected studies. Forest plots, funnel plots, and Begg's rank correlation were also performed on the included articles. Results: A total of 983 patients were contained in the 9 studies that satisfied the eligibility criteria. The meta-analysis showed that, compared with the control group, the glucocorticoid group had significantly improved the VA (MD: -0.25, 95% CI [-0.45, -0.05], P = 0.02), VF (MD: -0.50, 95% CI [-0.94, -0.07], P = 0.02), and RNFL (MD: -14.10, 95% CI [-26.41, -1.79], P = 0.02) in NAION patients and had a high improvement rate of VA (RR 1.31, 95% CI [1.12, 1.52], P = 0.0005). No significant publication bias was observed in our study. Discussion. Our research preliminarily confirmed the effectiveness of glucocorticoids for NAION treatment, but more high-quality RCTs focusing on the hormone adverse reactions should be performed to verify our conclusions.

Efficacy of Treatments in Nonarteritic Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis.

BACKGROUND: Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) is the second most common cause of optic nerve-related permanent visual loss in adults. AIM: We aimed to analyze the efficacy of the noninvasive and minimally invasive therapeutic options of NAION. METHODS: We performed a systematic literature search in MEDLINE, EMBASE, and CENTRAL from inception to 10 June 2019 to identify the studies that report on the effect of different therapies on visual acuity (VA) and visual field (VF). Weighted mean difference (WMD) with 95% confidence interval (CI) was calculated for these outcomes. The efficacy of steroids was investigated in quantitative, oxygen, steroid plus erythropoietin (EPO), levodopa/carbidopa, memantine, and heparin-induced extracorporeal LDL/fibrinogen precipitation (HELP) therapies and other therapeutic modalities in qualitative synthesis. RESULTS: Thirty-two studies were found to be eligible. We found that steroid therapy compared to control did not improve VA (p = 0.182, WMD = 0.14, 95% CI: -0.07, 0.35) or VF (p = 0.853, WMD = 0.16, 95% CI: -1.54, 1.86). Qualitative analysis could be performed for oxygen, steroid plus EPO, and HELP as well, however, none of them showed VA and VF benefit. Two individual studies found memantine and levodopa beneficial regarding VA. CONCLUSION: Our systematic review did not reveal any effective treatment. Further investigations are needed to find therapy for NAION.

Heterozygous factor V Leiden mutation manifesting with combined central retinal vein occlusion, cilioretinal artery occlusion, branch retinal artery occlusion, and anterior ischaemic optic neuropathy: a case report.

BACKGROUND: Our purpose was to describe a patient who developed combined central retinal vein occlusion (CRVO), cilioretinal artery occlusion, branch retinal artery occlusion (BRAO), and anterior ischaemic optic neuropathy (AION) followed by CRVO in the second eye because of the heterozygous factor V Leiden (FVL) mutation. CASE PRESENTATION: A 39-year-old female with a history of recurrent pregnancy losses presented with acute blurred vision in the right eye (RE), with visual acuity limited to counting fingers. She was diagnosed with combined impending CRVO, cilioretinal artery occlusion, BRAO, and AION. The results of thrombophilia testing, not including the FVL mutation, were negative. Retinal atrophy with vascular attenuation and optic disc pallor developed after resolution of acute retinal findings. Nine months after initial presentation, the patient developed an impending CRVO in the left eye (LE), with a secondary progression to a complete CRVO causing a decrease in best corrected visual acuity (BCVA) to 20/40. The patient was determined to be heterozygous for the FVL mutation. She subsequently was treated with acenocoumarol. At the last follow-up visit, the BCVA was 20/400 in the RE and 20/20 in the LE, and there was a complete resolution of the acute CRVO findings in the LE. CONCLUSION: Our case shows that the heterozygous FVL mutation may manifest with combined retinal vascular occlusion involving multiple sites in both eyes. Early recognition of such an inherited thrombophilic disorder is important because it implies the need for long-term anticoagulative therapy to reduce the patient's risk of recurrent, sight-threatening and life-threatening thrombotic events.

The Protective Effects of n-Butylidenephthalide on Retinal Ganglion Cells during Ischemic Injury.

Clinically, acute ischemic symptoms in the eyes are one of the main causes of vision loss, with the associated inflammatory response and oxidative stress being the key factors that cause injury. Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common type of ischemic optic neuropathy (ION); however, there are still no effective or safe treatment options to date. In this study, we investigated the neuroprotective effects of n-butylidenephthalide (BP) treatment in an experimental NAION rodent model (rAION). BP (10 mg/kg) or PBS (control group) were administered on seven consecutive days in the rAION model. Rats were evaluated for visual function by flash visual evoked potentials (FVEPs) at 4 weeks after NAION induction. The retina and optic nerve were removed for histological examination after the rats were euthanized. The molecular machinery of BP treatment in the rAION model was analyzed using Western blotting. We discovered that BP effectively improves retinal ganglion cell survival rates by preventing apoptotic processes after AION induction and reducing the inflammatory response through which blood-borne macrophages infiltrate the optic nerve. In addition, BP significantly preserved the integrity of the myelin sheath in the rAION model, demonstrating that BP can prevent the development of demyelination. Our immunoblotting results revealed the molecular mechanism through which BP mitigates the neuroinflammatory response through inhibition of the NF-κB signaling pathway. Taken together, these results demonstrate that BP can be used as an exceptional neuroprotective agent for ischemic injury.

Combination Therapy with Intravitreal Triamcinolone Acetonide and Oral Levodopa for the Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy: A Pilot Study.

Purpose: To determine the clinical effectiveness of combination therapy with intravitreal injection of triamcinolone acetonide (IVITA) and oral levodopa in eyes affected by nonarteritic anterior ischemic optic neuropathy (NAION). Methods: Longitudinal study involving 45 eyes of 45 patients with NAION who were evaluated within 14 days of NAION onset. The treatment group received an IVITA 4 mg/0.1 mL followed by 25 mg carbidopa/100 mg levodopa (Sinemet 25-100) 3 times daily for 12 weeks and the control group was untreated. Best-corrected visual acuity (BCVA) converted to logarithmic minimum angle of resolution (logMAR), visual field (VF) grades based on automated or Goldman perimetry, and mean retinal nerve fiber layer (RNFL) thickness measured on optical coherence tomography were assessed at the initial visit, 1, 3, and 6 months after NAION attack. Results: At the first visit and 6 months after NAION onset, the mean logMAR BCVA in the treatment group was significantly better than the control group (P < 0.05). BCVA was not significantly different between onset and the 6-month visit for both the control and the treatment group; however, the change in BCVA after 6 months was significantly greater in the treatment group compared with the control group (P = 0.007). Concomitant systemic disease, the changes in VF grades, and RNFL thickness from initial to 6 months after NAION onset were not significantly different between 2 groups. Conclusions: Combination therapy with IVITA and oral levodopa/carbidopa appears to be effective in the treatment of recent-onset NAION.

Visual Recovery with Iloprost Added to Corticosteroids in a Case of Giant Cell Arteritis.

INTRODUCTION: To date, corticosteroids remain the cornerstone treatment of ocular involvement of GCA, and no other treatment has proven to be effective in this setting. We herein report on a unique case of GCA with ocular involvement worsening despite high dose corticosteroids and recovering with intravenous iloprost. CASE REPORT: A 70-year-old man presented with acute vision loss in his left eye related to anterior ischemic optic neuropathy. The diagnosis of giant-cell arteritis was confirmed by a temporal artery biopsy. Despite intravenous pulse methylprednisolone for 3 days then oral prednisone at 60 mg/day, the patient developed from day 5 fluctuating vision loss in the right eye, related to ocular ischemia by occlusion of the ophthalmic artery, and responsive to hyperhydration. Iloprost, an analog of prostacyclin PGI2, was then administered intravenously for 5 days and resulted in a stable improvement in visual acuity in the right eye. CONCLUSION: This case highlights the potential role of vasodilatator agents in giant cell arteritis with ocular involvement.

Protective Effect of Pioglitazone on Retinal Ganglion Cells in an Experimental Mouse Model of Ischemic Optic Neuropathy.

The aim was to assess the protective effect of pioglitazone (PGZ) on retinal ganglion cells (RGCs) after anterior ischemic optic neuropathy (AION) in diabetic and non-diabetic mice. Adult C57BL/6 mice with induced diabetes were divided into three groups: group 1: oral PGZ (20 mg/kg) in 0.1% dimethyl sulfoxide (DMSO) for 4 weeks; group 2: oral PGZ (10 mg/kg) in 0.1% DMSO for 4 weeks; and group 3: oral DMSO only for 4 weeks (control group). Two weeks after treatment, AION was induced through photochemical thrombosis. For non-diabetic mice, adult C57BL/6 mice were divided into four groups after AION was induced: group 1: oral DMSO for 4 weeks; group 2: oral PGZ (20 mg/kg) in 0.1% DMSO for 4 weeks; group 3: oral PGZ (20 mg/kg) in 0.1% DMSO + peritoneal injection of GW9662 (one kind of PPAR-γ inhibitor) (1 mg/kg) for 4 weeks; group 4: peritoneal injection of GW9662 (1 mg/kg) for 4 weeks; One week after the induction of AION in diabetic mice, apoptosis in RGCs was much lower in group 1 (8.0 ± 4.9 cells/field) than in group 2 (24.0 ± 11.5 cells/field) and 3 (25.0 ± 7.7 cells/field). Furthermore, microglial cell infiltration in the retina (group 1: 2.0 ± 2.6 cells/field; group 2: 15.6 ± 3.5 cells/field; and group 3: 14.8 ± 7.5 cells/field) and retinal thinning (group 1: 6.7 ± 5.7 µm; group 2: 12.8 ± 6.1 µm; and group 3: 15.8 ± 5.8 µm) were also lower in group 1 than in the other two groups. In non-diabetic mice, preserved Brn3A+ cells were significantly greater in group 2 (2382 ± 140 Brn3A+ cells/mm2, n = 7) than in group 1 (1920 ± 228 Brn3A+ cells/mm2; p = 0.03, n = 4), group 3 (1938 ± 213 Brn3A+ cells/mm2; p = 0.002, n = 4), and group 4 (2138 ± 126 Brn3A+ cells/mm2; p = 0.03, n = 4), respectively; PGZ confers protection to RGCs from damage caused by ischemic optic neuropathy in diabetic and non-diabetic mice.

Simultaneous Bilateral Primary Occlusion of the Ophthalmic Artery due to Florid Giant Cell Arteritis.

PURPOSE: To report a case of simultaneous bilateral ophthalmic artery occlusion in diagnosed giant cell arteritis (GCA). OBSERVATIONS: A 77-year-old male patient presented to the emergency department with simultaneous vision loss in both eyes for 3 hours. Headache at both temples and jaw claudication had been present for 3 weeks. Laboratory values demonstrated an initially increased C-reactive protein (CRP) of 202.0 mg/L and an erythrocyte sedimentation rate (ESR) of 100 mm within the first 20 minutes. Duplex sonography of the right and left temporal arteries revealed a "halo sign." A case of GCA was suspected, and intravenous high-dose methylprednisolone therapy was immediately administered. The clinical examination revealed a bilateral central retinal artery occlusion and fluorescein angiography showed a hot optic disc in the right eye and patchy choroidal hypoperfusion in both eyes. Biopsy of the left temporal artery was performed, which confirmed a florid temporal arteritis with complete thrombotic occlusion of the vascular lumen. Despite a good response to the administered therapy (CRP 17.0 mg/L 1 week after initiation), the visual prognosis was significantly limited through retinal and optic nerve involvement. By the follow-up examination 8 weeks later, the near visual acuity was 20/400 in the right and left eye at a distance of 16 inches. CONCLUSION AND IMPORTANCE: We hereby present a simultaneous bilateral ophthalmic artery occlusion as a rare complication of GCA. The combination of central retinal artery occlusion, arteritic anterior ischemic optic neuropathy, and choroidal hypoperfusion suggests an acute inflammatory involvement of the ophthalmic artery. In cases of the slightest suspicion of giant cell arteritis, an immediate high-dose steroid therapy initiation is of utmost importance.

[Ischemic optic neuropathy despite pulse methylprednisolone therapy in a giant cell arteritis patient with perineural optic nerve enhancement].

A 76-year-old woman with a 1-month history of headache, jaw claudication, scalp tenderness, and blurred vision was admitted to our hospital. Erythrocyte sedimentation rate was highly elevated. Brain MRI showed marked perineural optic nerve enhancement and superficial temporal artery enhancement bilaterally. Neuro-ophthalmic examination detected left dominant decline in critical fusion frequency whereas visual acuity, visual fields, and ophthalmoscopy were normal. Intravenous pulse methylprednisolone was administered for 3 days to treat suspected giant cell arteritis (GCA); however, visual acuity in the left eye declined and horizontal hemianopia developed. Ophthalmoscopy revealed pallid optic disc edema on the left. Histopathologic examination of a right temporal artery biopsy specimen showed intimal thickening, mild mural inflammation consisting predominantly of lymphocytes with occasional giant cells, and focal disruption of the internal elastic lamina, consistent with GCA. Perineural optic nerve enhancement on contrast-enhanced MRI may be a valuable clue for diagnosing ischemic optic neuropathy and may indicate the need for urgent treatment.

Approaches to Potentiated Neuroprotective Treatment in the Rodent Model of Ischemic Optic Neuropathy.

Nonarteritic anterior ischemic optic neuropathy (NAION) commonly causes sudden optic nerve (ON)-related vision loss. The rodent NAION model (rAION) closely resembles NAION in presentation and physiological responses. We identified early rAION-associated optic nerve head (ONH) inflammatory gene expression responses and the anti-inflammatory prostaglandin PGJ2's effects on those responses. We hypothesized that blocking pro-inflammatory prostaglandin (PGE2) production by inhibiting monoacylglycerol lipase or cyclooxygenase activity and co-administering PGJ2 would potentiate RGC survival following ischemic neuropathy. Deep sequencing was performed on vehicle- and PGJ2-treated ONHs 3d post-rAION induction. Results were compared against responses from a retinal ischemia model. Animals were treated with PGJ2 and MAGL inhibitor KML29, or PGJ2 + COX inhibitor meloxicam. RGC survival was quantified by stereology. Tissue PG levels were quantified by ELISA. Gene expression was confirmed by qPCR. PGJ2 treatment nonselectively reduced inflammatory gene expression post-rAION. KML29 did not reduce PGE2 1d post-induction and KML29 alone increased RGC loss after rAION. Combined treatments did not improve ONH edema and RGC survival better than reported with PGJ2 alone. KML29's failure to suppress PGE2 ocular synthesis, despite its purported effects in other CNS tissues may result from alternative PG synthesis pathways. Neither KML29 nor meloxicam treatment significantly improved RGC survival compared with vehicle. While exogenous PGJ2 has been shown to be neuroprotective, treatments combining PGJ2 with these PG synthesis inhibitors do not enhance PGJ2's neuroprotection.

Intravitreal triamcinolone injections in non-arteritic anterior ischemic optic neuropathy - A retrospective report.

BACKGROUND: Non-arteritic anterior ischemic optic neuropathy (NAION) is a common cause of vision loss but no treatment has demonstrated its efficiency. A preliminary study showed an improvement on the visual acuity (VA) in a group of patients who received intravitreal administration of triamcinolone acetonide (IVTA) versus a non-treated group. In the present series, the visual outcome of IVTA in NAION was evaluated on a larger group of patients. METHODS: This retrospective, unmasked and non-randomized study took place at Reims University Hospital between 2009 and 2017. The data of consecutive patients presenting with isolated optic disc edema characteristic of recent NAION (<1month of visual acuity loss) were included. After informed consent, a single intravitreal injection of filtrated 4mg/0.1mL triamcinolone acetonide were administered. Twenty-seven control patients chose not to be injected and therefore served as controls. LogMar visual acuity (VA), VA rating (VAR) (1 line=0.1LogMAR=5 VAR letters), retinal nerve fiber layer thickness assessed by OCT and static visual field were evaluated at presentation, after 7days, after 3months and after 6months. RESULTS: Sixty-eight patients with NAION were evaluated. Forty-one received IVTA, 29 were injected within 15days after the onset of symptoms and 12 after 15days. There was a higher proportion of patients improving VA of 2 lines or more (10 or more VAR letters) in the injected group (49%) compared with the non-injected group (11%, P=0.019). Among the patients injected before 15days, the proportion improving for 2 lines or more (55% vs. 11%, respectively, P=0.013) and for 3 lines or more (45% vs. 11%, respectively, P=0.035) were significantly higher than in the non-injected group. Also, comparing the VA at presentation with the VA after 6months in the injected eyes, it improved significantly (P=0.003) and also in the subgroup injected within 15days (P=0.0007) but not in the injected group after 15days (P=0.801). Visual field improvement was only observed in the subgroup of patients injected within 15days with a significant improvement of the mean deviation (dB) within 6months (P=0.015). CONCLUSIONS: This follow-up study confirms the results of the previous series displaying an apparent benefit of intravitreal steroids injected in the acute phase of NAION. Only patients receiving IVTA within 15days from onset of NAION have a significant improvement of VA and visual field during the follow-up period of 6months.

Inhibition of Retinal Ganglion Cell Loss By a Novel ROCK Inhibitor (E212) in Ischemic Optic Nerve Injury Via Antioxidative and Anti-Inflammatory Actions.

Purpose: This study investigated the neuroprotective effects of administration of ROCK inhibitor E212 on ischemic optic neuropathy. Methods: Rats received an intravitreal injection of either E212 or PBS immediately after optic nerve infarct. The oxidative stress in the retina was detected by performing superoxide dismutase activity and CellROX assays. The integrity of retinal pigment epithelium was determined by staining of zona occludens 1. The visual function, retinal ganglion cell (RGC) density, and RGC apoptosis were determined by using flash visual-evoked potential analysis, retrograde FluoroGold labeling, and TdT-dUTP nick end-labeling assay. Macrophage infiltration was detected by staining for ED1. The protein levels of TNF-α, p-CRMP, p-AKT1, p-STAT3, and CD206 were evaluated using Western blotting. Results: Administration of E212 resulted in a 1.23-fold increase in the superoxide dismutase activity of the retina and 2.28-fold decrease in RGC-produced reactive oxygen species as compared to the levels observed upon treatment with PBS (P < 0.05). Moreover, E212 prevented the disruption of the blood-retinal barrier (BRB) in contrast to PBS. The P1-N2 amplitude and RGC density in the E212-treated group were 1.75- and 2.05-fold higher, respectively, than those in the PBS-treated group (P < 0.05). The numbers of apoptotic RGCs and macrophages were reduced by 2.93- and 2.54-fold, respectively, in the E212-treated group compared with those in the PBS-treated group (P < 0.05). The levels of p-AKT1, p-STAT3, and CD206 were increased, whereas those of p-PTEN, p-CRMP2, and TNF-α were decreased after treatment with E212 (P < 0.05). Conclusions: Treatment with E212 suppresses oxidative stress, BRB disruption, and neuroinflammation to protect the visual function in ischemic optic neuropathy.