[Effectiveness and interest of retrobulbar hyaluronidase injections in the treatment of blindness complicating facial hyaluronic acid injections: A literature review]. / Efficacité et intérêt des injections rétrobulbaires de hyaluronidase dans le traitement des cécités compliquant une injection faciale d'acide hyaluronique : revue de la littérature.

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.

Reversible acute blindness in suspected metformin-associated lactic acidosis: a case report.

BACKGROUND: Metformin is commonly used for the treatment of type 2 diabetes mellitus. Its multiple advantages include low risk of hypoglycemia, weight neutrality, low cost, and cardioprotective and anti-inflammatory effects. Renal insufficiency is one of the contraindications for its use. Inadvertent prescription in patients with renal insufficiency may lead to metformin-associated lactic acidosis, which brings a high risk of mortality. The early recognition and management of metformin-associated lactic acidosis are essential. CASE REPORT: We present the case of a 58-year-old Hui woman with a history of type 2 diabetes mellitus with nephropathy and heart disease for which she was treated with metformin, insulin, and heart medications. She developed nausea, vomiting, anion gap metabolic acidosis due to hyperlactatemia, and acute kidney injury. She was hospitalized to receive intravenous hydration and correction of metabolic acidosis after she suddenly developed blindness. The diagnostic workup ruled out central causes and her symptoms resolved briefly after continuous venovenous hemodialysis was initiated, confirming the diagnosis of metformin-associated lactic acidosis. CONCLUSIONS: Metabolic disruption can cause acute blindness. Metabolic acidosis in a patient with a history of metformin intake should suggest the possibility of metformin-associated lactic acidosis, which must be treated immediately, without waiting for the results of other examinations, especially in patients with sudden blindness. Further study of reversible blindness-associated severe metabolic acidosis is needed.

Steroid-induced glaucoma: an avoidable cause of irreversible blindness.

A man in his 70s on regular follow-up with an ophthalmologist for 10 years presented with blurry vision in his right eye for 4 days. He was diagnosed with elevated intraocular pressure (IOP) bilaterally 18 months earlier and treated with antiglaucoma eye-drops. On direct questioning, he admitted to using fixed combination tobramycin 0.3%/dexamethasone 0.1% eye-drops frequently to relieve ocular redness and discomfort in both eyes for 3.5 years without his ophthalmologist's knowledge. Examination disclosed markedly elevated IOP, advanced optic disc cupping and tunnel vision due to steroid-induced glaucoma bilaterally. After cessation of the eye-drops and 2 weeks of antiglaucoma therapy, his IOP returned to normal and his visual field remained stable for 4 years.Our case highlights the danger of habitual self-treatment of prescription medications containing corticosteroids and the importance of taking a detailed medication history in the diagnosis and management of steroid-induced glaucoma.

Simulation of long-term impact of intravitreal anti-VEGF therapy on patients with severe non-proliferative diabetic retinopathy.

OBJECTIVE: A simulation model was constructed to assess long-term outcomes of proactively treating severe non-proliferative diabetic retinopathy (NPDR) with anti-vascular endothelial growth factor (anti-VEGF) therapy versus delaying treatment until PDR develops. METHODS AND ANALYSIS: Simulated patients were generated using a retrospective real-world cohort of treatment-naive patients identified in an electronic medical records database (IBM Explorys) between 2011 and 2017. Impact of anti-VEGF treatment was derived from clinical trial data for intravitreal aflibercept (PANORAMA) and ranibizumab (RISE/RIDE), averaged by weighted US market share. Real-world risk of PDR progression was modelled using Cox multivariable regression. The Monte Carlo simulation model examined rates of progression to PDR and sustained blindness (visual acuity <20/200) for 2 million patients scaled to US NPDR disease prevalence. Simulated progression rates from severe NPDR to PDR over 5 years and blindness rates over 10 years were compared for delayed versus early-treatment patients. RESULTS: Real-world data from 77 454 patients with mild-to-severe NPDR simulated 2 million NPDR patients, of which 86 680 had severe NPDR. Early treatment of severe NPDR with anti-VEGF therapy led to a 51.7% relative risk reduction in PDR events over 5 years (15 704 early vs 32 488 delayed), with a 19.4% absolute risk reduction (18.1% vs 37.5%). Sustained blindness rates at 10 years were 4.4% for delayed and 1.9% for early treatment of severe NPDR. CONCLUSION: The model suggests treating severe NPDR early with anti-VEGF therapy, rather than delaying treatment until PDR develops, could significantly reduce PDR incidence over 5 years and sustained blindness over 10 years.

Central retinal artery occlusion following facial injection of hyaluronic acid.

A 57-year-old woman with no premorbidities presented with symptoms of sudden painless vision loss in the right eye (RE). Best-corrected visual acuity in the RE was counting fingers to. A relative afferent pupillary defect was observed in the RE. Ocular fundus examination of RE was suggestive of central retinal artery occlusion. Systemic evaluation was normal. The most interesting fact in this case is that a hemorrhagic edema in the right glabellar region was the basis for the diagnostic suspicion. The patient recognized the loss of vision 24 h after hyaluronic acid injection as a facial rejuvenation treatment.

Delayed reversal of methanol-induced blindness in an adult by a combination of erythropoietin and a high dose of methylprednisolone: a case report.

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.

Central Retinal Vein Occlusion 36-Month Outcomes with Anti-VEGF: The Fight Retinal Blindness! Registry.

PURPOSE: To analyze the 3-year outcomes in a broad population of patients starting VEGF inhibitors for central retinal vein occlusion (CRVO) in routine clinical practice. DESIGN: Observational database study. PARTICIPANTS: Overall, 527 treatment-naïve CRVO eyes that commenced VEGF inhibitors between December 1, 2010 and 2018 were tracked in the Fight Retinal Blindness! registry. METHODS: Longitudinal models were used to plot changes in visual acuity (VA) and central subfield thickness (CST). MAIN OUTCOME MEASURES: Mean change in VA from baseline to 36 months, injections, visits, completion, switching, and suspensions of therapy > 180 days at the final review. RESULTS: Overall (527 eyes) mean VA change (95% confidence interval [CI]) was + 10 (7, 12) letters, 37% had final VA ≥ 70 and 30% ≤ 35 letters, mean CST changed -306 µm. Completers (257/527, 49%) had mean 36-month changes in VA and CST of + 12 letters and -324 µm with a median of 18 injections at 26 visits. The adjusted mean VA change was similar to each VEGF inhibitor (mean, + 11.4 letters) despite a greater reduction in CST with aflibercept (-310 µm) versus ranibizumab (-258 µm) versus bevacizumab (-216 µm; P < 0.001). Eyes with baseline VA that was trial-eligible (19-73 letters; 356/527, 68%) gained 7 letters, very poor (< 19 letters; 129/527, 24%) gained 22 letters, or very good (> 73 letters; 42/527, 8%) lost 7 letters. Switching (160/527, 30%) was most often to aflibercept (79 eyes). By using suspensions and discontinuation reasons, we identified similar proportions had ceased therapy (154/527, 29%) and were still receiving it at 36 months (165/527, 31%). Only 62/527 eyes (12%) had resolution of macular edema without treatment for > 6 months. CONCLUSIONS: Patients with CRVO that commenced VEGF inhibitors in routine care for whom follow-up was available had VA improvements of around 12 letters at 3 years, but with > 50% lost to follow-up, the VA outcome for the entire group was likely worse. The choice of VEGF inhibitor influenced CST but not VA outcomes. We estimated that around half of the eyes were still receiving injections after 36 months. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Cilioretinal artery occlusion in antiphospholipid syndrome and the decision to anticoagulate.

A patient in her late 50s with antiphospholipid syndrome presented to general ophthalmology clinic for annual hydroxychloroquine retinopathy screening. She had taken 400 mg hydroxychloroquine daily for over a decade. She denied any visual changes and visual acuity was 20/20. Her examination and fundus photos were normal, but macular optical coherence tomography of the right eye demonstrated inner retinal atrophy and visual field tests revealed a corresponding paracentral scotoma, consistent with a prior cilioretinal artery occlusion. Prior testing from visits with other ophthalmologists revealed that this occlusion had occurred previously, but she had only been informed of not having hydroxychloroquine retinopathy. The possibility of vision loss prompted her to reconsider her prior decision to discontinue anticoagulation. This case demonstrates how anchoring bias may lead clinicians astray, and how the risk of blindness is a strong motivator for patients regarding anticoagulation.

Effectiveness of retrobulbar hyaluronidase in the treatment of visual loss caused by periocular hyaluronic acid injection. A systematic review.

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.

Filler-induced blindness "seen" by ophthalmologists: Case presentation and treatment algorithm.

PURPOSE: Filler-induced blindness (FIB) is the most threatening complication following periocular injection. To date, no standard of care has been established. The goal of this study is to report a new case of FIB with partial visual recovery and present our personalized algorithm for treatment based on fluorescein angiography findings. MATERIALS AND METHODS: Case report with 24 months follow-up and treatment algorithm. RESULTS: Our patient experienced complete vision loss to no light perception following forehead lipofilling. Retinal angiography identified a posterior ciliary artery occlusion. Antiplatelet medication, steroids and intraocular pressure lowering medications were administrated, followed by hyperbaric oxygen treatment (HBOT). Visual acuity improved to +0.8 logMar. The HBOT treatment was monitored by fluorescein angiogram. Based on this case and on the ophthalmic literature on retinal and ciliary artery occlusion, we established a personalized FIB protocol guided by fluorescein angiography. CONCLUSION: Although prevention remains the best treatment, all physicians should be prepared to manage FIB. Prompt management at the office guided by written protocols, as well as emergency kits, are essential. In referral centers, personalized treatment should be undertaken based on fluorescein angiography findings.

Incidence, Risk Factors, and Outcomes of Rhegmatogenous Retinal Detachment after Intravitreal Injections of Anti-VEGF for Retinal Diseases: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To report the estimated incidence, probability, risk factors, and 1-year outcomes of rhegmatogenous retinal detachment (RRD) in eyes receiving intravitreal injections (IVTs) of VEGF inhibitors for various retinal conditions in routine clinical practice. DESIGN: Retrospective analysis of data from a prospectively designed observational outcomes registry: the Fight Retinal Blindness! PARTICIPANTS: Eyes of patients starting IVTs of VEGF inhibitors (ranibizumab, aflibercept, or bevacizumab) for neovascular age-related macular degeneration, diabetic macular edema, or retinal vein occlusion from January 1, 2006, to December 31, 2020. All eyes that developed RRD within 90 days of IVTs were defined as cases with RRD and were matched with control eyes. METHODS: Estimated incidence, probability, and hazard ratios (HRs) of RRD were measured using Poisson regression, Kaplan-Meier survival curve, and Cox proportional hazards models. Locally weighted scatterplot smoothing curves were used to compare visual acuity (VA) between cases and matched controls. MAIN OUTCOME MEASURES: Estimated incidence of RRD. RESULTS: We identified 16 915 eyes of 13 792 patients who collectively received 265 781 IVTs over 14 years. Thirty-six eyes were reported to develop RRD over the study period. The estimated incidence (95% confidence interval [CI]) per year per 1000 patients and per 10 000 injections was 0.77 (0.54-1.07) and 1.36 (0.95-1.89), respectively. The probability of RRD did not significantly increase at each successive injection (P = 0.95) with the time of follow-up. Older patients (HR [95% CI] = 1.81 [1.21-3.62] for every decade increase in age, P < 0.01) were at a higher risk of RRD, whereas patients with good presenting VA (HR [95% CI] = 0.85 [0.70-0.98] for every 10-letter increase in VA, P = 0.02) were at a lower risk. Neither the type of retinal disease (P = 0.52) nor the VEGF inhibitor (P = 0.09) was significantly associated with RRD risk. Cases with RRD lost 3 lines of vision on average compared with the prior RRD VA and had significantly fewer injections than matched controls over the year after the RRD. CONCLUSIONS: Rhegmatogenous retinal detachment is a rare complication of VEGF inhibitor IVT in routine clinical practice with poor visual outcomes at 1 year.

Advancing a Human Onchocerciasis Vaccine From Antigen Discovery to Efficacy Studies Against Natural Infection of Cattle With Onchocerca ochengi.

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.

THREE-YEAR TREATMENT OUTCOMES OF AFLIBERCEPT VERSUS RANIBIZUMAB FOR DIABETIC MACULAR EDEMA: Data from the Fight Retinal Blindness! Registry.

PURPOSE: Compare the 3-year outcomes of ranibizumab versus aflibercept in eyes with diabetic macular edema in daily practice. METHODS: This was a retrospective analysis of naive diabetic macular edema eyes starting intravitreal injections of ranibizumab (0.5 mg) or aflibercept (2 mg) from January 1, 2013 to December 31, 2017 that were collected in the Fight Retinal Blindness! Registry. RESULTS: We identified 534 eyes (ranibizumab-267 and aflibercept-267) of 402 patients. The adjusted mean (95% confidence interval) visual acuity change of +1.3 (-0.1 to 4.2) letters in the ranibizumab group and +2.4 (-0.2 to 5.1) letters (P = 0.001) in the aflibercept group at 3 years was not clinically different. However, the adjusted mean CST change seemed to remain significantly different throughout the 3-year period with higher reductions in favor of aflibercept (-87.8 [-108.3 to -67.4] µm for ranibizumab vs. -114.4 [-134.4 to -94.3] for aflibercept; P < 0.01). When baseline visual impairment was moderate (visual acuity ≤68 Early Treatment Diabetic Retinopathy Study letters), we found a faster improvement in visual acuity in eyes treated with aflibercept up until 18 months of treatment than eyes treated with ranibizumab, which then stayed similar until 36 months of treatment, whereas there was no apparent difference when baseline visual impairment was mild (visual acuity ≥69 Early Treatment Diabetic Retinopathy Study letters). The rate of serious adverse events was low. CONCLUSION: Aflibercept and ranibizumab were both effective and safe for diabetic macular edema over 3 years.

Ocular Complications Post-Cosmetic Periocular Hyaluronic Acid Injections: A Systematic Review.

BACKGROUND: With the global rise in the use of hyaluronic acid (HA) fillers as a minimally invasive cosmetic procedure, significant adverse effects such as vascular compromise and blindness have become common. Hence, we present the first systematic review aimed to investigate ocular complications secondary to a facial HA injection and to understand the presentation, cause, management, and outcome of these complications. METHODS: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used to report this review. A systematic search was performed in July 2021 for published literature using the PubMed, MEDLINE, and Cochrane databases. The following terms were used: facial fillers, facial injections, hyaluronic acid, blindness, ophthalmoplegia, diplopia, ptosis, ophthalmic artery occlusion, posterior ciliary artery occlusion, and ocular ischemic syndrome. RESULTS: A total of 2496 publications were searched, and 34 articles published between January 2000 and July 2021 were included. Twenty-seven case reports and seven case series were evaluated. The nose was the most common site of injection (n = 25; 40.67%). Ocular pain was the most common initial symptom of ocular complications (n = 13, 22.41 %). The most common complication was vision loss (n = 17, 50%). The majority of patients received hyaluronidase, aspirin, and steroids. Regarding the outcome, 15 (45.45%) of the published studies showed no improvement in complications even after management. CONCLUSION: HA is gaining popularity in cosmetic applications. Post-HA ocular complications nearly always have an immediate onset. Proper knowledge of potential adverse events is crucial for clinicians to attempt to decrease complications and improve outcomes. 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.

Facial Injections and Blindness: A Review on Anatomy.

ABSTRACT: With the sudden emergence of new medical aesthetic fillers, the number of fillers injected worldwide has exploded, but there are also worrying risks in the pursuit of beauty. At present, many cases of blindness caused by injection of aesthetic fillers have been reported. Most of the cases are caused by irreversible vascular embolism. This is a rare yet greatly feared complication of using facial cosmetic fillers. This article reviewed and analyzed the literature and summarized the changes in the anatomical structure of facial blood vessels related to blindness during facial injection.

Unexpected amaurosis occurring after peribulbar anesthesia: Exploring the causes in two cases.

Peribulbar anesthesia (PB) is known to be safer than retrobulbar (RB) anesthesia. To our knowledge, no amaurosis has been described after PB. We report here the cases of two patients who underwent PB before membrane peeling. The injections were administered with a 25-gauge, 22-mm bevel disposable needle. The anesthetic used was ropivacaine 1% with a volume of 8 ml and 75 µg of clonidine as an adjuvant (7.5 µg/ml). Given that complete akinesia was not achieved, a second injection of 2 ml was administered in the supero-medial injection site. Thirty minutes after the PB, the first patient experienced amaurosis with no light perception (LP). The ophthalmic examination was normal. Visual acuity recovered after 1 day. Regarding the second patient, the loss of VA was observed 20 min after the PB. IOP was 20 mmHg. The anterior segment and fundus exam were normal. Rubin found the PB technique to be as effective and safer than RB injection, as the needles are not supposed to enter the RB space and Davis and Mandel found no amaurosis after PB. PB is administered via the extraconal injection of an anesthetic agent. These amaurosis might be explained by the fact that some anesthetic may have penetrated the RB space. In cases where two PB injections are administered, the anatomy is expected to change due to the volume effect of the first injection. The second injection is higher risk as it is administered closer to the optic nerve.

Visual loss after aesthetic facial filler injection: a literature review on an ophthalmologic issue.

Dermal filler injection is among facial rejuvenation treatments that have been increasingly used. Despite being a minimally invasive procedure, it can lead to severe complications such as blindness. A review of all cases of filler- -induced visual loss in the world literature was conducted to summarize the mechanisms, anatomical considerations, and clinical ophthalmologic course, current strategies of prevention and management, and trends over the years. We identified 233 cases of filler-induced visual loss, and 172 patients had a severe visual impairment in at least one eye. The typical patients are young women who received injections of hyaluronic acid or autologous fat in the glabella or nose, and the typical presentations were sudden ocular pain, ptosis, and ophthalmoplegia due to vascular occlusion. The findings of this study also suggest an increase in the number of unlicensed professionals performing the procedure. Even though the continued development of dermal fillers has improved the treatment options available, further studies and strategies are necessary to reduce the incidence and minimize the consequences of filler-induced visual loss.