ATYPICAL FORMS OF EYE TOXOPLASMOSIS IN CHILDHOOD. CASE REPORTS.

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.

Evaluation of presentation, treatment and outcome in hypertensive emergency in dogs and cats: 15 cases (2003-2019).

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.

Bevacizumab for blinding eye disease – is it time for the PBS to list for off-label use?

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.

Creation of a neovascular age-related macular degeneration national database using a web-based platform: Fight Retinal Blindness Spain. Report 1: Visual outcomes.

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.

Cosmetic Filler Blindness: Recovery After Repeated Hyaluronidase Injections.

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.

INTERNATIONAL IMPACT OF THE COVID-19 PANDEMIC LOCKDOWN ON INTRAVITREAL THERAPY OUTCOMES: Fight Retinal Blindness Registry.

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.

Características clínico-demográficas de pacientes con ceguera irreversible en el Servicio de Oftalmología General de la Clínica Belén, Coronel Oviedo, Paraguay desde febrero del 2018 a febrero del 2019 / Clinical and demographic characteristics of patients with irreversible blindness at the General Ophthalmology Service of the "Clínica Belén", Coronel Oviedo, Paraguay from February 2018 to February 2019

Según la Organización Mundial de la Salud, la ceguera está definida como la agudeza visual inferior a 3/60 (20/400) en el mejor ojo y un campo visual menor a 10° desde el punto central de fijación. El objetivo de este trabajo fue describir las características clínico demográficas de pacientes con diagnóstico de ceguera irreversible atendidos en el Servicio de Oftalmología General de la Clínica Belén - Coronel Oviedo (Paraguay). Estudio observacional, descriptivo y retrospectivo de corte transversal. Se realizó la revisión retrospectiva de las historias clínicas de los pacientes con diagnóstico de ceguera irreversible atendidos en el Servicio de Oftalmología General de la Clínica Belén, entre el 1 de febrero 2018 y el 28 de febrero 2019. Se analizaron la edad, sexo, escolaridad, procedencia, agudeza visual, comorbilidades y etiología de la deficiencia visual. El análisis estadístico fue mediante el cálculo de frecuencias absolutas y relativas para las variables cualitativas, y el promedio y desviación estándar para las cuantitativas. Se estudiaron 78 pacientes, con predominio del sexo masculino (56,4%), edad de 71 a 95 años (43,6%) y primaria incompleta (41%). La hipertensión arterial (55,6%) fue la principal comorbilidad y glaucoma (43,6%) la etiología de ceguera más frecuente. El glaucoma fue más frecuente en varones que en mujeres (59% vs 32%) y en pacientes mayores de 50 años de edad (50%). En esta serie, los pacientes presentaron ceguera irreversible bilateral, en mayor frecuencia en varones, mayores de 50 años de edad, hipertensión como comorbilidad y glaucoma como etiología más frecuente

According to the World Health Organization, blindness is defined as visual acuity less than 3/60 (20/400) in the better eye and a visual field less than 10 ° from the central fixation point. The objective was to describe the clinical demographic characteristics of patients with a diagnosis of irreversible blindness treated at the General Ophthalmology Service of the "Clínica Belén" - "Coronel Oviedo" (Paraguay). This was an observational, descriptive and retrospective cross-sectional study. A retrospective review of the medical records of patients with a diagnosis of irreversible blindness treated at the General Ophthalmology Service of the "Clínica Belén" between February 1, 2018 and February 28, 2019 was carried out. Age, sex, education, origin, visual acuity, comorbidities and etiology of visual impairment were analyzed. The statistical analysis was through the calculation of absolute and relative frequencies, as well as the average and standard deviation. Seventy eight patients were studied, with a slight predominance of males (56.4%), aged 71 to 95 years (43.6%), incomplete primary school (41%) and from "Coronel Oviedo" (25.6 %) and surroundings. Arterial hypertension (55.6%) was the main comorbidity and glaucoma (43.6%) the most frequent blindness etiology. Glaucoma was more common in male patients than female patients (59% and 32%, respectively) and in patients older than 50 years of age (50%). In this series, patients presented bilateral irreversible blindness, more frequent in men, older than 50 years of age, hypertension as comorbidity and glaucoma as the most frequent etiology

Infliximab-induced optic neuritis.

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.

Twelve-month outcomes of intra-vitreal anti-VEGF agents for treatment-naïve neovascular age-related macular degeneration eyes: French data from the fight for retinal blindness!

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.

Vision treatment strategy for acute blindness in adolescent female with diffuse leptomeningeal glioneuronal tumor.

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.

Examining the Role of Retrobulbar Hyaluronidase in Reversing Filler-Induced Blindness: A Systematic Review.

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.

Outcomes of cataract surgery in eyes with diabetic macular oedema: Data from the Fight Retinal Blindness! Registry.

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.

Evaluation of Intraarterial Thrombolysis in Treatment of Cosmetic Facial Filler-Related Ophthalmic Artery Occlusion.

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.

Severe Vitamin A Deficiency After Biliopancreatic Diversion.

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.

Assessing Retrobulbar Hyaluronidase as a Treatment for Filler-Induced Blindness in a Cadaver Model.

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.

Retrobulbar Injection for Hyaluronic Acid Gel Filler-Induced Blindness: A Review of Efficacy and Technique.

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 .

Stimulus-Responsive Hydrogel for Ophthalmic Drug Delivery.

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.

Role of Retrobulbar Hyaluronidase in Filler-Associated Blindness: Evaluation of Fundus Perfusion and Electroretinogram Readings in an Animal Model.

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.

Light Perception Vision Recovery After Treatment for Calcium Hydroxylapatite Cosmetic Filler-Induced Blindness.

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.