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Background: With the global increase in the use of injectable fillers, more cases with serious adverse events such vision loss are being reported. This article aims to review the cases of hyaluronic acid (HA) filler-related vision loss and to discuss the potential efficacy of hyaluronidase (HYASE) treatment via different given methods., Methods: A total of 29 articles presenting 144 cases of HA filler-related vision loss were included in this study., Results: Most cases of HA filler-related vision impairment were reported from China, followed by Korea. The majority of cases were seen in women. The nose, forehead and glabella were the most commonly injection sites. All cases had vision impairment and nearly all cases were unilateral with immediate onset of visual signs and symptoms. Ophthalmic artery occlusion (OAO) and central retinal artery occlusion (CRAO) were the two most commonly involved arterial obstruction patterns featured with a very poor prognosis followed by branch retinal artery occlusion (BRAO), the most favorable involved arterial pattern for a better prognosis. HYASE given subcutaneously and intra-arterially helped with visual recovery to different degrees, while retrobulbar HYASE seemed to be less helpful., Conclusion: Complications after HA-based filler injection are extremely rare but can cause disastrous visual impairment. HYASE given subcutaneously and intra-arterially helped with visual recovery to different extents, and the efficacy might be reinforced when performed together, while retrobulbar HYASE seemed to be less helpful. However, to accurately access the efficacy of HYASE via different administration methods, further randomized controlled trials are needed., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Aims: We present the clinical spectrum, the initial clinical presentation with management trends in treating 14 Vogt-Koyanagi-Harada (VKH) disease cases in a tertiary center in the Northern part of Malaysia., Case Series: There were 14 cases of Vogt-Koyanagi-Harada (VKH) disease retrospectively reviewed over five years (from 2015 to 2020). The mean age at presentation was 37.7 years (range 21-64 years), with female predominance (85.7%). All cases presented with acute uveitic stage and bilateral eye involvement. Of them, 11 (78.6%) were probable VKH, and three (21.4%) were incomplete VKH. All patients attended with acute panuveitis at first presentation. The main posterior segment involvement was disc edema in 57.1% (16 out of 28 eyes) and exudative retinal detachment (ERD) in 35.7% (10 out of 28 eyes). Most of them presented with blindness (3/60 and worse) and moderate visual impair- ment (6/18-6/60); 35.71% each, followed by mild visual impairment (6/12-6/18), and severe visual impairment (6/60-3/60); 7.1% each. Ten patients (71.4%) required combination second-line immunomodulatory treatment during subsequent visits, and only four patients (28.6%) responded well to corticosteroid therapy. Most of the cases achieved no visual impairment (64.3%), followed by mild visual impairment (21.4%) and moderate visual impairment (14.3%), and none were severe or blind at the end of follow-up., Conclusion: VKH is a potentially blinding illness if there is inadequate control of the disease in the acute stage. Most of our patients achieved good visual outcomes with early immunomodulatory treatment and systemic corticosteroids.

Introduction: Hyaluronic acid injections are becoming increasingly common among both the general public and the medical community, but they are not without risks. The occurrence of blindness, although rare, is a tragic event for both the patient and the practitioner. One of the treatments proposed in the literature is to inject hyaluronidase as close as possible to the site of ischemia, retrobulbarly. The aim of our study is to evaluate the effectiveness and potential benefits of retrobulbar hyaluronidase injections., Materials and Methods: A literature review was conducted using the PubMed database. Only articles addressing retrobulbar hyaluronidase injections for the treatment of blindness following hyaluronic acid injections were included., Results: We identified 12 case reports or series, comprising a total of 16 patients. Among these 16 patients, 3 regained their vision. Hyaluronidase was injected between 20minutes and 7days after the onset of the complication, with injected doses ranging from 3×150IU to 3×1500IU., Discussion: Literature reveals only 3 cases of successful treatment out of the 16 reported injections. The time interval before retrobulbar injection, as well as the dose and the experience of the injecting practitioner, may influence the success rate of this treatment. Other treatments, such as intravascular hyaluronidase injections, remain to be explored., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: The clinical manifestation following methanol toxicity accounts for a life-threatening problem that contributes to metabolic disorders, neurological complications, blindness, and even death. There is no completely effective treatment to retain the patient's vision. Herein, we apply a new therapeutic strategy for the recovery of bilateral blindness in a patient who had ingested methanol., Case Presentation: A 27-year-old Iranian man with complete bilateral blindness was referred 3 days after accidental ingestion of methanol to the poisoning center at Jalil Hospital, Yasuj, Iran, in 2022. After taking his medical history, performing neurologic and ophthalmologic examinations, and routine laboratory tests, ordinary management was undertaken and counterpoisons were given for 4-5 days; however, the blindness did not reverse. Following the 4-5 days of unsuccessful standard management, he was given ten doses of subcutaneous erythropoietin 10,000 IU/12 hours twice daily, folinic acid 50 mg/12 hours, and methylprednisolone 250 mg/6 hours for 5 days. After five days, vision of both eyes recovered, reaching 1/10 in the left and 7/10 in the right eye. He remained under daily supervision until his release from the hospital, and he was discharged from the hospital 15 days post admission. In outpatient follow-up, his visual acuity was improved without having any side effects at 2 weeks after discharge., Conclusion: A combination of erythropoietin and a high dose of methylprednisolone were useful for relieving the critical optic neuropathy and improved the optical neurological disorder following methanol toxicity., (© 2023. The Author(s).)

Purpose: To report a case of posterior scleritis following COVID-19 vaccination., Study Design: Case report., Results: A 78-year-old female presented with headache and right-sided visual loss 10 days after the second dose of COVID-19 vaccine. 'Examination showed disc oedema and a serous retinal detachment. B-scan ultrasound showed thickening of the posterior sclera with retroscleral fluid. CT head with venogram excluded venous sinus thrombosis. The patient's condition improved rapidly with oral corticosteroids with restoration of vision and resolution of disc swelling and serous detachment by 4 weeks., Conclusions: Posterior scleritis should be considered in patients presenting with headaches and blurred vision following vaccination. Timely diagnosis and treatment with corticosteroids can prevent permanent visual loss.

Objectives: Hypertensive emergency is well recognised in human medicine, yet there is limited veterinary evidence. This study aimed to determine the presentation, treatment and outcome in dogs and cats with hypertensive emergency., Materials and Methods: A retrospective case series of dogs and cats with hypertensive emergency identified as follows: acute history with non-invasive Doppler systolic blood pressure greater than 180 mmHg and target organ damage including acute onset seizures, altered mentation with or without lateral recumbency or blindness. Data collected included signalment, history, physical examination and clinicopathological findings, systolic blood pressure, antihypertensive treatment and outcome., Results: Seven dogs and eight cats were included presenting with seizures (n=9), blindness (n=4), altered mentation with (n=2) or without (n=2) lateral recumbency. Median age was 9 years (range 1 to 15) and duration of clinical signs before presentation was 1.5 days (range 1 to 15). Median systolic blood pressure on presentation was 230 mmHg (range 190 to 300). Amlodipine was the most common first-line agent (n=10), followed by hydralazine (n=4) and hypertonic saline (n=1). Aetiology of hypertensive emergency was acute kidney injury (n=9), idiopathic hypertension (n=3), hyperthyroidism (n=1), lymphoma (n=1) and suspected cutaneous and renal glomerular vasculopathy (n=1). Five cats and three dogs survived to discharge with an overall survival of 53.3%., Clinical Significance: Hypertensive emergencies had various presenting signs in this series. AKI was considered to be the cause of hypertension in the majority of patients. Further evaluation of treatment for hypertensive emergencies is warranted, considering almost half of the cases did not survive to discharge., (© 2022 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

Introduction: Blindness after periocular cosmetic filler injection is a rare but devastating complication. Complication management protocols recommend injecting retrobulbar hyaluronidase if visual loss related to accidental intravascular injection of hyaluronic acid occurs. Given the dramatic increase in cosmetic filler injections and the variety of professionals that can deliver them, it is reasonable to assume that the incidence of complications will rise significantly., Objective: To evaluate if there is evidence-based efficacy of retrobulbar hyaluronidase injection in visual loss secondary to periocular cosmetic filler injection., Material and Methods: The authors performed a search of English and Spanish language articles following the PRISMA statement published on the use of retrobulbar hyaluronidase to reverse vision loss precipitated by hyaluronic acid gel fillers. Articles reviewed included case reports/series and experimental investigations. We identified a total of 13 patients in this review following defined inclusion and exclusion criteria. Finally, we included 15 articles in the study, 12 of them were cases / case series. The 2 remaining articles are experimental studies in animals with a control group, in which after causing selective occlusion of the ophthalmic artery, serial injections of retroocular hyaluronidase are administered with control of visual function., Results: Of the 15 articles included in the study, we studied 17 patients treated with retrobulbar hyaluronidase for hyaluronic acid-induced blindness. Improvement was demonstrated in 3 cases. Animal studies demonstrate variable data are provided regarding the recovery of visual acuity., Conclusions: There is no confirmed evidence of retrobulbar hyaluronidase injection effectiveness in treating visual loss due to accidental intravascular injection of hyaluronic acid. More studies are needed to show the efficacy of hyaluronidase as a treatment for blindness caused by hyaluronic acid., (Copyright © 2022 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Mass drug administration (MDA) programs are a critical component of efforts to treat and eliminate trachoma, a leading cause of blindness worldwide. Despite the importance of these programs for individual and community health, pregnant and breastfeeding women have historically been excluded from treatment in these programs. Countries with active MDA programs also tend to have high fertility rates, and thus women may be left untreated for years at a time. Not only do these women suffer from the symptoms of disease (pain and eventual blindness), but also failure to include the entire population in drug administration programs leaves pockets of infection in the community, risking outright failure of eradication efforts. The medication used most commonly, azithromycin, appears to be safe for use in pregnancy and breastfeeding. The time has come to include pregnant and breastfeeding women in MDA programs, not just for them, but also for their communities.

Retinopathy of prematurity (ROP) is a rare proliferative ocular disorder in preterm infants. Because of the advancements in neonatal care, the incidence of ROP has increased gradually. Now, ROP is one of the leading causes of blindness in children. Preterm infants with immature retinal development are exposed to supplemental oxygen inside an incubator until their cardiopulmonary system is adequately developed. Once they are returned to room air, the relatively low oxygen level stimulates various angiogenesis factors initiating retinal neovascularization. If patients with ROP are not offered adequate and timely treatment, they can experience vision loss that may ultimately lead to permanent blindness. Although laser therapy and anti-vascular endothelial growth factor agents are widely used to treat ROP, they have limitations. Thus, it is important to identify novel therapeutics with minimal adverse effects for the treatment of ROP. To date, various pharmacologic and non-pharmacologic therapies have been assessed as treatments for ROP. In this review, the major molecular factors involved in the pathogenesis of ROP, currently offered therapies, therapies under investigation, and emerging novel therapeutics of ROP are discussed.

Aim: To present an outline of acquired atypical forms of ocular toxoplasmosis (OT) in childhood, with reference to the 100th anniversary of the discovery of this etiology by Professor Janků from Czechoslovakia, who was first to describe the clinical congenital picture of OT characterised by macular scar., Material and Methods: Symptoms of intraocular bilateral neuritis appeared in a 6-year-old girl, with visual acuity (VA) bilaterally 0.1. Toxoplasmic etiology was demonstrated in laboratory tests, and the patient was immunocompetent. Following treatment with macrolide antibiotic and parabulbar application of corticosteroid, the condition was normalised stably at VA 1.0 in both eyes. Bilateral retinal vasculitis was determined in an 8-year-old boy, with VA of 0.25 in the right eye and 0.25 in the left, with a medical history of strabismus detected after suffering from varicella. The examination for toxoplasmosis was negative, but pronounced general hypogammaglobulinaemia classes IgG, IgM and IgA was detected. Immunosuppressive and immunomodulatory therapy did not produce the desired effect, and the condition progressed to retinochoroiditis. Due to blindness and dolorous glaucoma, enucleation of the right eye was performed at the age of 15 years. Histologically toxoplasmic cysts with bradyzoites were detected, a subsequent laboratory test demonstrated toxoplasmic etiology upon a background of persistent regressing hypogammaglobulinaemia. General anti-toxoplasma and subsequent immunosuppressive treatment did not produce the desired effect, and at the age of 22 years the patient lost his sight also in the left eye., Conclusion: Atypical form of OT intraocular neuritis in an immunocompetent patient had a favourable course, whereas retinal vasculitis with retinochoroiditis in a temporarily immunocompromised patient ended in bilateral blindness.

BACKGROUND Metformin-associated lactic acidosis (MALA) is a relatively rare adverse effect of metformin therapy. It usually occurs in patients with metformin overdose or in those with underlying acute and/or chronic conditions resulting in impaired lactate metabolism. Among these, patients with acute kidney injury, heart failure, sepsis, and cirrhosis are the most vulnerable to MALA, even in the setting of appropriate therapy. The most common symptoms of MALA include nausea, vomiting, diarrhea, encephalopathy, hypothermia, respiratory failure, and hypotension. Blindness is a dramatic symptom that has been rarely reported with MALA. CASE REPORT We report a case of 78-year-old woman with history of type 2 diabetes mellitus with nephropathy for which she was treated with metformin and insulin. She developed nausea, non-bloody emesis, and watery diarrhea, which led to dehydration, anion gap metabolic acidosis due to hyperlactatemia, and acute kidney injury (AKI). She was hospitalized for i.v. hydration and further management when she suddenly developed blindness. The diagnostic work-up ruled out central causes and her symptoms resolved briefly after continuous renal replacement therapy (CRRT) was initiated, confirming the diagnosis of MALA. CONCLUSIONS By reporting this case, we wish to increase awareness about MALA symptoms, its diagnosis, and the importance of early recognition and initiation of treatment among clinicians involved in the care of patients with chronic kidney disease (CKD) who take metformin for diabetes mellitus. Although rare, this metformin adverse effect can present dramatically and can be distressing for both patient and treating team.

Human onchocerciasis is a devastating neglected tropical disease caused by infection of the filarial nematode Onchocerca volvulus . The infection can cause irreversible visual impairment or blindness and stigmatizing dermatitis. More than 32 million people were estimated to be infected with O. volvulus in Africa, and 385,000 suffered from blindness. Even though the implementation of mass drug administration (MDA) with ivermectin has reduced the global prevalence of onchocerciasis, O. volvulus infection remains challenging to control because MDA with ivermectin cannot be implemented in endemic areas co-endemic with loiasis due to the risk of severe adverse events. There is also emerging drug resistance to ivermectin that further complicates the elimination of onchocerciasis. Thus, the development of a vaccine that would induce protective immunity and reduce infection burden is essential. Efforts to develop prophylactic and/or therapeutic vaccines for onchocerciasis have been explored since the late 1980s by many researchers and entities, and here we summarize the recent advances made in the development of vaccines against the infection of O. volvulus and onchocerciasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhan, Bottazzi, Hotez and Lustigman.)

Background: To study the visual outcomes of neovascular AMD (nAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs at national level., Methods: Multicenter national database of nAMD eyes treated with anti-VEGF intravitreal injections (ranibizumab, aflibercept, bevacizumab) in fixed bimonthly (FB) or treat-and-extend (TAE) regimens. Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) ETDRS letters at baseline and subsequent visits, number of injections and visits data were collected using a validated web-based tool (Fight Retinal Blindness!)., Results: 1273 eyes (1014 patients) were included, 971 treatment naïve (TN) and 302 previously treated (PT). Baseline VA (mean ± SD) was 57.5 (±19.5) and 62.2 (±17) (p > 0.001), and 24 months final VA was 60.4 (±21.2) and 58.8 (±21.1) (p = 0.326), respectively. Mean VA change at 12/24 months was +4.2/+2.9 letters in TN eyes and +0.1/-3.4 letters in PT eyes (p < 0.001/p < 0.001). The percentage of ≥15 letters gainers/losers at 24 months was 24.8%/14.5% in TN, and 10.3%/15.7% in PT eyes. The median number of injections/visits at 12 months was 7/9 in TN and 6/8 in PT (p = 0.002/p < 0.001) and at 24 months was 11/16 in TN and 11/14 in PT (p = 0.329/p < 0.001). Study drugs included ranibizumab (39.5%), aflibercept (41.2%) and bevacizumab (19.3%)., Conclusion: Independent, large-scale national audits are feasible if committed health care professionals are provided with efficient information technology systems to do them. The results described here represent an adequate measurement of the quality of care delivered nationwide and benchmark the clinical management of nAMD at a country level compared to other real-world international cohorts., (© 2022 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

Anti-vascular endothelial growth factor eye injections have become the most accepted and effective treatment for some of the leading causes of blindness. Aflibercept (Eylea; Bayer) is the most expensive item on the Pharmaceutical Benefits Scheme, (PBS) with ranibizumab (Lucentis; Roche/Novartis) ranked eighth. In 2011 the pharmaceutical cost for these treatments was A$237 million - now the figure is A$665 million and climbing. Bevacizumab (Avastin; Roche) is part of the original molecular lineage for a group of biologic agents, which were originally designed for cancer therapy. It is now administered worldwide on an off-label basis and in very large numbers for retinal vascular disease. It has a proven efficacy and safety profile. Bevacizumab is thirty times cheaper than the Therapeutic Goods Administration (TGA)-approved alternatives and its use could reduce PBS costs by hundreds of millions of dollars. Should the TGA be the sole arbiter in the approval of drugs, or should alternative bodies have some say in the approval of off-label usage under such compelling circumstances? Legislation for this approach has been approved in France, the UK, and Italy. Only by eliminating the legal risk to authorising bodies and physicians, and the financial disincentive to the patient associated with off-label use, will drugs such as bevacizumab be more widely adopted.

Purpose: To evaluate the impact of the COVID-19 pandemic lockdowns on the outcomes of eyes treated for neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion in eight countries., Methods: A multicenter international database study of 5,782 eyes (4,708 patients) receiving intravitreal antivascular endothelial growth factor injections before, during, and after national lockdowns. The baseline visit was defined as the last visit within 3 months before lockdown, and prelockdown and postlockdown periods were defined as 6 months before and after the lockdown date., Results: Eyes with neovascular age-related macular degeneration (n = 4,649) lost vision in all countries in proportion to the reduced number of injections. The mean visual acuity change postlockdown ranged from -0.4 to -3.8 logarithm of the minimum angle of resolution letters, and the median number of injections/visits decreased from 4-5/4-7 to 2-4/2-4 postlockdown. The diabetic macular edema (n = 654) and retinal vein occlusion (n = 479) eyes' mean visual acuity change ranged from -2.8 to +1.7 letters and -1.6 to +0.1 letters, and the median number of injections/visits decreased from 2.5-5/4-6 to 1-3/2-4 and from 3-5.5/4-5 to 1-3.5/2-3.5, respectively. The 6-month dropout rates postlockdown were 20% for neovascular age-related macular degeneration, 27% for diabetic macular edema, and 28% for retinal vein occlusion., Conclusion: This international study provides estimates of the impact of COVID-19 pandemic lockdown on intravitreal therapy and suggests that prioritizing neovascular age-related macular degeneration eyes seems appropriate.

Background: The rise of cosmetic injectables has involved new clinical scenarios related to complications. The scenario of hyaluronic acid (HA) aesthetic interventional-induced visual loss has become more recognized. Although this complication is rare, there can be delayed recognition and treatment, with limited opportunity to evaluate potential treatments and establish best practice guidelines., Objectives: The authors report a case of documented visual recovery with extra-orbital and intra-orbital hyaluronidase. Central retinal artery occlusion is an ischemic event requiring urgent intervention. The authors hope to assist protocols being developed for HA aesthetic interventional-induced visual loss., Methods: Following loss of vision, 675 international units (IU) of hyaluronidase was given immediately to the injection site and extra-orbital area. Within 4 hours, 3000 IU intra-orbital and 1500 IU extra-orbital hyaluronidase were given., Results: Visual loss in a 38-year-old female, following ipsilateral nasal injection of 0.15 mL of HA filler Juvéderm Voluma via the nasal tip, was documented at no perception of light with afferent pupil defect, central retinal artery occlusion, and fundoscopy showing a cherry red spot. This was associated with cerebral irritation and magnetic resonance imaging ischemia. Hyaluronidase was injected as described above. The following day, visual acuity (VA) in the affected eye recovered to 6/18 with a relative superior visual field scotoma. The VA improved to 6/6 at 1 month., Conclusions: The authors believe immediate injection followed by high dose intra-orbital and extra-orbital injection of hyaluronidase had a positive effect in this case. Recovery of vision was remarkable, from no perception of light to 6/6, documented at a tertiary referral eye hospital., (© 2021 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

Pressure waves from explosions or other traumatic events can damage the neurons of the eye and visual centers of the brain, leading to functional loss of vision. There are currently few treatments for such injuries that can be deployed rapidly to mitigate damage. Brain-derived neurotrophic factor (BDNF) and activation of its receptor tropomycin-related kinase B (TrkB) have neuroprotective effects in a number of degeneration models. Small molecule activators of TrkB, such as N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC), cross the blood-brain and blood-retina barriers after systemic administration. We characterize the effects of blast-induced ocular trauma on retinal and visual function. We show that systemic administration of HIOC, a potent small molecule activator of the BDNF/TrkB receptor, preserves visual function in mice exposed to ocular blast injury. The HIOC treatment for one week preserves visual function for at least four months. The HIOC treatment effectively protected vision when the initial dose was administered up to 3 h after blast, but not if the initial treatment was delayed for 24 h. We provide evidence that the therapeutic effect of HIOC is mediated by activation of BDNF/TrkB receptors. The results indicate that HIOC may be useful for managing ocular blast injury and other forms of traumatic optic neuropathy.

Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide. We conducted an observational study of 262 consecutive individuals (n = 344 eyes) with ocular toxoplasmosis who were followed over a 34-month period. Most subjects were T. gondii IgG + /IgM- (n = 242; 92.4%; 317 eyes), and 140 eyes (40.7%) had active lesions. For eyes in which retinal lesions were active at recruitment and best-corrected visual acuity (BCVA) could be measured (n = 133), 21.0% (n = 28) remained blind (BCVA below 20/400) after inflammation resolved. In these eyes, atypical ocular toxoplasmosis (OR 4.99; 95% CI 1.14-22.85; p = 0.0330), macular lesion (OR 9.95; 95% CI 2.45-47.15; p = 0.0019) and any complication (OR 10.26; 95% CI 3.82-30.67; p < 0.0001) were associated with BCVA below 20/200. For eyes with only inactive lesions at recruitment and BCVA measured (n = 178), 28.1% (n = 50) were blind. In these eyes, having at least one lesion larger than one disc-diameter (OR 6.30; 95% CI 2.28-22.46; p = 0.0013) and macular lesion (OR 5.69; 95% CI 2.53-13.54; p < 0.0001) were associated with BCVA below 20/200. Older age (OR 1.02; 95% CI 1.00-1.05; p = 0.0493) and active disease at presentation (OR 4.74; 95% CI 1.95-12.91; p = 0.0011) were associated with recurrences. Additional clinical attention should be directed towards patients with risk factors for poor visual outcome.

Wolfram syndrome (WS) is a monogenic progressive neurodegenerative disease and is characterized by various neurological symptoms, such as optic nerve atrophy, loss of vision, cognitive decline, memory impairment, and learning difficulties. GLP1 receptor agonist liraglutide and BDNF mimetic 7,8-dihydroxyflavone (7,8-DHF) have had protective effect to visual pathway and to learning and memory in different rat models of neurodegenerative disorders. Although synergistic co-treatment effect has not been reported before and therefore the aim of the current study was to investigate liraglutide, 7,8-DHF and most importantly for the first time their co-treatment effect on degenerative processes in WS rat model. We took 9 months old WS rats and their wild-type (WT) control animals and treated them daily with liraglutide, 7,8-DHF or with the combination of liraglutide and 7,8-DHF up to the age of 12.5 months (n = 47, 5-8 per group). We found that liraglutide, 7,8-DHF and their co-treatment all prevented lateral ventricle enlargement, improved learning in Morris Water maze, reduced neuronal inflammation, delayed the progression of optic nerve atrophy, had remyelinating effect on optic nerve and thereby improved visual acuity in WS rats compared to WT controls. Thus, the use of the liraglutide, 7,8-DHF and their co-treatment could potentially be used as a therapeutic intervention to induce neuroprotection or even neuronal regeneration.

Competing Interests: None

Traumatic optic neuropathy is sinister sequelae of craniofacial trauma leading to vision loss. The decision between early medical or surgical intervention is usually individualised. Visual evoked potentials may guide the treatment plan. We describe a young male presenting 5 days after a road traffic accident with no perception of light vision in the right eye. He was managed medically with high dose of intravenous steroids. At the 3-month follow-up, he reported a reversal of vision loss with return of visual acuity to 3/60, which improved to 6/36 at 5 months and remained stable at 8 months., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Antitumour necrosis factor alpha agents are important treatments in many inflammatory conditions including rheumatoid arthritis, psoriatic arthritis and the inflammatory bowel diseases. However, there have been case reports of optic neuritis and other demyelinating diseases as complications of these agents. This case report presents a patient with ulcerative colitis on infliximab who presented with sudden onset mono-ocular visual field loss and highlights the diagnosis and management of infliximab-induced optic neuritis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Diffuse leptomeningeal glioneuronal tumor with the first symptom of acute rapid blindness in both eyes are rare in adolescents. We present a case of an adolescent female without a history of cancer who developed a dramatic loss of vision and eventually blindness, and was diagnosed as diffuse leptomeningeal glioneuronal tumor by cerebrospinal fluid cytology and enhanced MRI. In order to save vision, under the condition of ineffective dehydration treatment, timely emergency surgery to implant Ommaya sac drainage cerebrospinal fluid. According to the pathophysiological mechanism of cerebral edema, we added Edaravone to scavenge oxygen free radicals, Alprostadil to improve microcirculation, Monosialotetrahexosylganglioside nutrient nerve, Butylphthalide to promote collateral circulation, combined with hyperbaric oxygen and acupoint injection of Anisodine. Finally, the patient's vision returned to normal. Conclusion: when dehydration treatment is ineffective, timely surgery to reduce intracranial pressure, combined with comprehensive treatment, can effectively save vision.

Introduction: To describe the one-year functional outcomes of treatment-naïve neovascular age-related macular degeneration (nAMD) treated with anti-VEGF agents at the Dijon University Hospital Ophthalmology Department., Methods: Real-life interventional study including all treatment-naïve nAMD patients from January 2016 to December 2018 in the Ophthalmology Department of Dijon University Hospital. Data were retrospectively collected from the Fight Retinal Blindness! (FRB!) registry. At baseline, medical history, visual acuity (VA), type of lesion and activity on angiography and optical coherence tomography (OCT), and treatment were recorded. On follow-up, VA, lesion activity and treatment were recorded., Results: Three-hundred twenty eyes of 259 patients were included, of which 65.6% were female and with a mean age of 80.1±11.1 years. Mean VA (standard deviation, SD) at baseline was 53.2 ETDRS letters (25.3). All patients received anti-VEGF injections, of which 164 eyes (51.2%), 152 eyes (47.5%) and 4 eyes (1.2%) were treated with aflibercept, ranibizumab and bevacizumab, respectively. A total of 198 eyes of 169 patients completed the 12-month follow-up, with a median (first quartile, third quartile) of 12 visits (10, 13). At one year (n=198), the overall mean VA gain [95% CI] was +3.3 ETDRS letters [0.7, 5.9] and 173 (87.4%) of the treated eyes did not lose 15 or more letters. We found no statistically significant difference in mean VA gain between aflibercept and ranibizumab., Conclusion: This real-world study confirmed the efficacy of anti-VEGF agents in nAMD and the feasibility of analyzing data in an international registry., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Neisseria gonorrhoeae bacteria are acknowledged as an urgent threat to human health because this species has developed resistances to all of the antibiotics used clinically to treat its infections. N. gonorrhoeae causes the sexually transmitted disease gonorrhoea, but also causes blindness when the bacteria infect the eyes. Infants are particularly susceptible, acquiring the infection from their mothers at birth. We have shown that the monoglyceride monocaprin rapidly kills N. gonorrhoeae and other bacterial species and is non-irritating in ocular assays. Here we show that the physical and chemical properties of monocaprin make it ideal for use in a thickened eye drop formulation to combat eye infections. Monocaprin-containing formulations were assessed using analytical techniques and for antimicrobial activity in vitro and in ex vivo infections. Monocaprin-containing formulations retained activity after three years and are non-irritating, unlike preparations of povidone iodine in our assays. A recommended formulation for further development and investigation is 0.25% monocaprin in 1% HPMC with 1% polysorbate 20.

A 53-year-old immunocompromised woman developed acute left eye blindness and paraparesis suspected to be due to neuromyelitis optica (NMO). During treatment for NMO, right eye blindness and progressive multiple cranial neuropathies developed. Cerebrospinal fluid polymerase chain reaction (PCR) revealed Varicella zoster virus (VZV). This case emphasizes the importance of considering VZV in individuals, particularly the immunocompromised, presenting with a constellation of neurological signs and symptoms, even in the absence of rash.

Importance: There are limited data on real-world outcomes of cataract surgery in eyes receiving intravitreal treatments for diabetic macular oedema (DMO)., Background: Cataract surgery may exacerbate oedema in some eyes with DMO resulting in inferior outcomes., Design: Matched, case-controlled retrospective study of observational data in routine clinical practice., Participants: Eyes receiving intravitreal treatments for DMO tracked in the Fight Retinal Blindness! Registry., Methods: Eyes that underwent cataract surgery were identified and matched 1:1 with phakic controls also receiving intravitreal injections for DMO. We also assessed potential factors that were associated with better visual acuity (VA) outcomes., Main Outcome Measures: Change in VA 6 months after cataract surgery., Results: Cataract surgery was identified in 208 eyes of 156 patients of which 147 eyes had 6 months of observations before and after surgery. The mean VA 6 months after surgery improved by 10.6 letters and was similar to their matched phakic controls (68.8 vs 69.2 letters; P = 0.8). Mean CST both 6 months before (341 μm) and after (360 μm) surgery were similar (P = 0.08). However, these eyes had thicker maculae and they received more injections than their matched phakic controls both before and after surgery. Eyes with worse VA before surgery and those that had received intravitreal treatment in the 4 weeks preceding surgery were more likely to gain vision., Conclusions and Relevance: Visual outcomes of cataract surgery in eyes receiving intravitreal therapy for DMO were reasonably better. Their maculae were thicker and required more injections in the 6 months before and after surgery than their phakic controls., (© 2019 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To provide a systematic review of the literature concerning retrobulbar hyaluronidase injections as a treatment for hyaluronic acid gel filler-induced blindness and evaluate the level of evidence for this proposed therapy., Methods: The authors performed a search of English language articles published on the use of retrobulbar hyaluronidase to reverse vision loss precipitated by hyaluronic acid gel fillers. Articles reviewed included case reports/series, experimental investigations, expert opinion commentaries, and major reviews. To date, there have been no case-control, cohort, or randomized control studies to evaluate this treatment. Five anecdotal descriptions of hyaluronic acid gel filler blindness treated specifically with retrobulbar hyaluronidase were identified, for a total of 9 patients. One hundred twelve articles in total on this treatment and related topics, including filler-induced blindness and alternative treatments, were identified and reviewed., Results: Of the 9 documented cases of patients treated with retrobulbar hyaluronidase for hyaluronic acid-induced blindness, visual improvement was demonstrated in 2 cases. The successes, however, are undermined by inconsistent pretreatment ophthalmic assessment and documentation. Animal studies demonstrate mixed results. Laboratory studies document the inability of hyaluronidase to cross the optic nerve sheath., Conclusions: There is not currently enough evidence to support retrobulbar hyaluronidase as a treatment for filler-induced blindness. Additional studies are needed to further evaluate its efficacy and explore alternative treatments.

Background: With an increase in recent years in the number of people receiving cosmetic facial injection treatments of hyaluronic acid, the incidence of hyaluronic acid embolism has also increased commensurately. Hyaluronic acid embolism leads to serious complications, including blindness, eye and eyelid movement disorders, skin necrosis, and cerebral embolism. However, there is a lack of robust clinical evidence regarding the benefits of treatment for hyaluronic acid embolism by intraarterial thrombolysis therapy., Methods: This study included 24 patients with a decrease in visual acuity and other complications induced by facial hyaluronic acid injection. Patients underwent emergency intraarterial thrombolysis therapy by injection of hyaluronidase (500 to 1500 units) alone or hyaluronidase (750 to 1500 units) combined with urokinase (100,000 to 250,000 units), followed in both cases by a general symptomatic treatment and nutritional therapy., Results: Ten (42 percent) of 24 patients ultimately had improvements to visual acuity, even when the clinical application of the thrombolytic treatments had passed the recommended window for optimal treatment. In all cases, patients' facial skin necrosis was restored to nearly normal appearance. In addition, the authors found that hyaluronidase combined with urokinase was a more effective therapy than hyaluronidase alone., Conclusions: The authors' results indicate that intraarterial thrombolysis therapy is beneficial to patients suffering from blindness induced by hyaluronic acid embolism. The therapy was shown to be worthy of clinical application because it alleviated the impairment to patients' vision and was also beneficial in the recovery from other serious complications, including eye movement disorder, eye edema, headaches, and skin necrosis., Clinical Question/level of Evidence: Therapeutic, IV.

Background: Retrobulbar injection of hyaluronidase is a proposed but unproven treatment for blindness induced by hyaluronic acid gel fillers. This study examines the viability of this treatment by determining whether hyaluronidase can diffuse through the dural sheath of the optic nerve to clear a filler-mediated occlusion of the central retinal artery., Methods: Six human cadaveric optic nerves were studied in vitro. One optic nerve was selected as a control and maintained at physiologic temperature, without any exposure to hyaluronic acid gel or hyaluronidase. Another optic nerve was randomly selected to simulate the filler-induced central retinal artery occlusion with subsequent retrobulbar hyaluronidase injection. To simulate a central retinal artery occlusion, this experimental nerve and additional controls were injected with hyaluronic acid gel. These hyaluronic acid gel-injected nerves were then either injected directly with hyaluronidase to establish a control for intraneural hyaluronidase exposure, or immersed in undiluted hyaluronidase to simulate retrobulbar hyaluronidase injection. To control for passive diffusion of hyaluronic acid gel from neural parenchyma, one nerve was immersed in saline. Following fixation, the nerves were grossly and microscopically assessed for the quantity and distribution of hyaluronic acid., Results: Intact hyaluronic acid gel was observed grossly and microscopically in the control optic nerves injected directly with filler and not with hyaluronidase. The control optic nerve injected with intraneural hyaluronidase exhibited partial digestion of the filler. Immersion in undiluted hyaluronidase led to no apparent gross or microscopic digestion of injected intraneural hyaluronic acid gel., Conclusion: Hyaluronidase does not demonstrate the ability to cross the dural sheath of the optic nerve, suggesting that retrobulbar hyaluronidase injection is unlikely to alleviate hyaluronic acid gel-mediated central retinal artery occlusion and blindness.

While blindness after hyaluronic acid gel filler injection occurs only very rarely, it represents a devastating complication for the patient and the surgeon. Retrobulbar injection with hyaluronidase is the only known potential means of reversing this adverse event. However, positive outcomes remain anecdotal. We have attempted to review the current literature regarding possible efficacy and detail the indications and technique to be utilized, if hyaluronidase retrobulbar injection is to be attempted. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Blindness and vision impairment are major global health problems. Effective ophthalmic drug delivery poses a significant challenge because of protective physiological barriers and various biological clearance mechanisms that result in extremely low ocular bioavailability. Over the past several decades, several safe and effective ophthalmic drug delivery approaches have been promoted to combat these problems and to improve ocular bioavailability. Among these approaches, the stimulus-responsive hydrogel for topical drug delivery has gained increasing attention because of its prolonged drug retention at the local site and enhanced ocular bioavailability. This review summarizes and presents recent advances and perspectives of a stimulus-responsive hydrogel for ophthalmic drug delivery., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

BACKGROUND Systemic lupus erythematosus (SLE) causes sight-threatening, ophthalmologic problems that are frequently challenging to manage. Optic neuropathy is a rare ophthalmological complication of SLE that can progress to total bilateral vision loss if not identified and treated rapidly. We describe a patient with SLE who presented with an acute, painless unilateral optic neuropathy who subsequently experienced partial recovery of vision when treated with high-dose intravenous corticosteroids. CASE REPORT A 44-year-old female with known SLE presented with 4 days of painless, complete, and gradual vision loss in the right eye. Initial ophthalmologic examination revealed no light perception, afferent pupil defect, 4+ optic disc swelling, and 1+ venous tortuosity of the right eye. No hemorrhage or exudates were noted. Diagnostic workup revealed a lupus flare with elevated inflammatory markers including elevated anti-nuclear antibody, anti-ds-DNA antibody, anti-Sm antibody, and anti-phospholipid IgG antibody. The diagnosis of optic neuropathy was clinically established, and the patient was treated with high-dose intravenous corticosteroids. Her vision improved, and she was transitioned to oral corticosteroids with eventual significant improvement in her vision. CONCLUSIONS Optic neuropathy is a rare and devastating ophthalmologic complication of SLE. The diagnosis can be made by linking key clinical findings on ophthalmologic examination with positive serological studies. If treated rapidly with immunosuppressive therapy, the vision loss can be reversed, and permanent blindness avoided. Although this rare complication is generally bilateral in nature, clinician must also be aware of unilateral disease and treat patients accordingly.

Biliopancreatic diversion is a surgical procedure that causes weight loss via volume restriction and malabsorption. It is now rarely performed due to the risk of severe nutritional deficiencies including vitamin A. We report a case of severe vitamin A deficiency due to malabsorption from a biliopancreatic diversion procedure for weight loss. By the time the patient presented to our department, she had developed blindness refractory to parenteral vitamin A treatment. A unique feature of her case is the development of a rash with vitamin A injections. This reaction has only been reported in one case series of 3 patients in the published literature. Her case highlights the importance of vitamin deficiency screening in patients after bariatric surgery, and her skin reaction to the injections is a unique side effect that is not frequently observed.

Purpose: Hyaluronic acid gel filler-associated blindness is an uncommon but devastating complication. Hyaluronidase can potentially dissolve intravascular filler and improve perfusion; however, its role in filler-associated blindness has yet to be determined. The purpose of this study is to determine the effect of retrobulbar hyaluronidase on hyaluronic acid gel-induced ophthalmic artery occlusion in a rabbit model., Methods: New Zealand red rabbits were used to simulate hyaluronic acid gel filler-associated vascular occlusive blindness. Ophthalmic artery occlusion and subsequent ischemia were confirmed by both retinal fundus photography and electroretinogram changes. Retrobulbar hyaluronidase 1,000 IU was injected 30 minutes after occlusion. Fundus photography and electroretinogram changes were recorded at 30, 60, 90, and 120 after administration of retrobulbar hyaluronidase., Results: A total of 6 rabbits were used, for a total of 12 eyes. Four eyes were used as controls. Of the 8 experimental eyes, 2 eyes had recorded partial occlusion and 6 eyes had fully occluded ophthalmic arteries by angiographic evaluation. One of the partially occluded eyes demonstrated some improvement in perfusion 60 minutes after injection of retrobulbar hyaluronidase; however, electroretinogram readings remained flat over the 120-minute period of observation. Six eyes with completely occluded ophthalmic arteries showed no improvement in retinal perfusion with corresponding flat electroretinogram readings at 120 minutes following retrobulbar hyaluronidase injection., Conclusions: In this rabbit model, 1,000 IU of retrobulbar hyaluronidase administered 30 minutes after occlusion failed to reverse obstruction or restore function following hyaluronic acid gel occlusion of the ophthalmic artery.

A 51-year-old woman presented with no light perception vision of the right eye 12 hours after another provider injected calcium hydroxylapatite into the glabella and dorsum of the nose. Exam and fluorescein angiography demonstrated optic nerve edema and choroidal hypoperfusion consistent with ischemia of the posterior ciliary circulation. The central retinal circulation appeared intact. One thousand two hundred units of retrobulbar hyaluronidase were injected urgently in several boluses. Oral prednisone and aspirin also were administered. Ocular massage was also initiated. One day later, visual acuity improved to light perception that remained stable at 3 months. Retrobulbar hyaluronidase injection, ocular massage, prednisone, and aspirin were correlated to recovery of light perception vision in this case of calcium hydroxylapatite filler embolization to the choroidal circulation. The mechanism for the recovery of some vision and the role of hyaluronidase and other medications remain uncertain. Further research in treatments for ophthalmic complications of facial fillers is warranted.

Oculomeningovascular amyloidosis is a variant of transthyretin (TTR) amyloidotic polyneuropathy, which is associated with blindness and brain ischemia, microhemorrages, and siderosis due to prominent production of the abnormal TTR in the eye and in the choroid plexuses. Tafamidis is a TTR stabilizer that is orally administered and, by interfering with amyloid fibril formation and deposition, is capable of slowing progression of TTR polyneuropathy and of early-stage cardiomyopathy. However, the ocular manifestations of amyloid deposition progressed despite tafamidis therapy in Val30Met TTR amyloidosis, and the effects of tafamidis on meningovascular amyloidosis are unknown. We observed failure of tafamidis to halt progression of oculomeningovascular amyloid deposition in a patient with familial Ala36Pro TTR amyloidosis. She received molecular diagnosis at age 24 and presented at age 26 with paresthesias of the lower limbs and bowel dysfunction. Echography showed minimal amyloid opacities in the corpus vitreum. Treatment with tafamidis meglumine was started. Sixteen months later, she complained of severe headache followed by left hemiparesthesias and numbness lasting 20 minutes. Magnetic resonance imaging showed multiple focal and diffuse hemosiderin deposits compatible with microbleeds and early siderosis. Echography showed a marked increase of "vitreal opacities." Our observation confirms that tafamidis fails in halting increase of vitreal amyloid deposits and indicates that it is presumably ineffective in preventing clinical onset due to progression of meningovascular amyloidosis. These failures may be due to the incapability of tafamidis to cross the blood-retina and blood-brain barriers. Therapeutic options targeting oculomeningovascular TTR amyloidoses in humans are required., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Ciliopathies are clinically overlapping genetic disorders involving structural and functional abnormalities of cilia. Currently, there are no small-molecule drugs available to treat ciliary defects in ciliopathies. Our phenotype-based screen identified the flavonoid eupatilin and its analogs as lead compounds for developing ciliopathy medication. CEP290, a gene mutated in several ciliopathies, encodes a protein that forms a complex with NPHP5 to support the function of the ciliary transition zone. Eupatilin relieved ciliogenesis and ciliary receptor delivery defects resulting from deletion of CEP290. In rd16 mice harboring a blinding Cep290 in-frame deletion, eupatilin treatment improved both opsin transport to the photoreceptor outer segment and electrophysiological responses of the retina to light stimulation. The rescue effect was due to eupatilin-mediated inhibition of calmodulin binding to NPHP5, which promoted NPHP5 recruitment to the ciliary base. Our results suggest that deficiency of a ciliopathy protein could be mitigated by small-molecule compounds that target other ciliary components that interact with the ciliopathy protein.

A 25-year-old male patient presented to the emergency department with the chief complaint of sudden blindness and was found to have suffered bilateral central retinal artery occlusion (CRAO). This process is most commonly the result of a thrombus or embolus that occludes the retinal artery, and normally presents in a single eye in patients older than 65 who are predisposed to vascular disease. Diagnosis relies most heavily upon funduscopic exam. Potential treatments involve ocular massage, acetazolamide, anterior chamber paracentesis and systemic or local fibrinolysis. Despite these interventions vision is often significantly and permanently impaired. This case underscores the importance of the emergency physician's ability to promptly perform and interpret the funduscopic exam in order to diagnose and evaluate CRAO., (Copyright © 2018. Published by Elsevier Inc.)

Background: We describe a 75-year-old woman who experienced vision loss in her left eye due to biopsy-proven giant cell arteritis (GCA). She subsequently developed pachymeningitis causing refractory headaches and bilateral optic neuropathy and maculopathy., Methods: Case report with literature review., Results: Eighteen months after the initial diagnosis of GCA, imaging studies in our patient demonstrated pachymeningeal enhancement, and meningeal biopsy confirmed lymphoplasmacytic tissue infiltrates with low frequencies of IgG4+ plasma cells. Laboratory investigation revealed the presence of 3 antiretinal antibodies and antimyeloperoxidase antibodies, consistent with autoimmune retinopathy. Treatment with B-cell-depleting anti-CD20 antibodies suppressed meningeal inflammation and prevented further vision loss., Conclusions: This case illustrates that bilateral vision loss and chronic headaches in patients with GCA may result from retina-directed autoimmunity and pachymeningitis.

Purtscher-like retinopathy, a rare manifestation of systemic thrombotic microangiopathy, is a potentially visually debilitating condition with no effective proven treatment. Distinct pathogenic pathways have been proposed as etiological factors. We revisit the etiology of Purtscher-like retinopathy based on the rapid response and profound visual improvement after initiation of systemic intravenous eculizumab, an inhibitor of the complement cascade, in a patient with Purtscher-like retinopathy secondary to familial atypical hemolytic uremic syndrome (aHUS) due to a mutation in complement factor H. We hypothesize that the efficacy of eculizumab in this patient provides evidence for pathogenic events in the retina similar to those encountered in the renal microvasculature of aHUS patients, namely complement-mediated thromboembolization as a result of activation of the complement cascade in endothelial cells with release of tissue factor and development and amplification of a procoagulant state. To the best of our knowledge, this is the first report in the literature of eculizumab as an effective therapeutic strategy in Purtscher-like retinopathy.

Purpose: To present our experience in the management of superior ophthalmic vein thrombosis (SOVT), which is a rare, but extremely serious condition if not recognized and managed promptly and appropriately., Methods: Two patients with septic and aseptic SOVT are presented. Clinical characteristics, radiographic features, management techniques, and outcomes are described., Results: In the first case thrombosis occurred as a complication of functional endoscopic sinus surgery. In the second case thrombosis occurred as a complication of untreated inflammatory bowel disease: ulcerative colitis. Both cases resulted with permanent unilateral blindness., Conclusion: SOVT is a rare entity. There are no guidelines, just recommendations for disease management. Based on our experience, broad-spectrum intravenous antibiotic, anticoagulation, and steroid therapy should be promptly introduced and if needed surgical intervention. SOVT can lead to devastating complications which include permanent loss of vision and in some cases a fatal outcome.