Intraocular cetuximab: Safety and effect on axial elongation in young Guinea pigs with lens-induced myopization.

This study aimed to examine the intraocular tolerability of the epidermal growth factor receptor antibody cetuximab, when applied intravitreally, and its effect on axial elongation. Guinea pigs aged 2-3 weeks were subjected to bilateral plano glasses and bilateral lens-induced myopization (LIM) as a single procedure for group I (n = 8) and group II (n = 8), respectively. In the animals of group III (n = 8), group IV (n = 8), and group V (n = 8), the right eyes of the animals, in addition to LIM, received four weekly intravitreal injections of cetuximab (Erbitux®) in doses of 6.25 µg, 12.5 µg, and 25 µg, respectively. As controls, the left eyes, in addition to LIM, received corresponding intraocular injections of phosphate-buffered saline. The animals underwent regular ophthalmoscopic examinations and biometry for axial length measurements. With increasing doses of cetuximab, the inter-eye difference in axial elongation (at study end, left eyes minus right eyes) were significantly the smallest in group I (0.00 ± 0.02 mm) and group II (-0.01 ± 0.02 mm), they were larger in group III (0.04 ± 0.04 mm) and group IV (0.10 ± 0.03 mm), and they were the largest in group V (0.11 ± 0.01 mm). The inter-eye difference in axial elongation enlarged (P < 0.001) with the number of injections applied. Retinal thickness at the posterior pole (right eyes) was significantly thicker in group V than in group II (P < 0.01). The density of apoptotic cells (visualized by TUNEL-staining) did not vary significantly between any of the groups (all P > 0.05). The results suggest that intravitreal injections of cetuximab in young guinea pigs with LIM resulted in a reduction in axial elongation in a dose-dependent and number of treatment-dependent manner. Intraocular toxic effects, such as intraocular inflammation, retinal thinning, or an increased density of apoptotic cells in the retina, were not observed in association with the intravitreally applied cetuximab.

The impact of SARS-Cov-2 infection on the periocular injection pain and hypersensitive reaction to botulinum toxin type A: results from clinical questionnaires.

Background: The COVID-19 pandemic has brought about significant changes in the medical field, yet the use of botulinum toxin type A has remained uninterrupted. Plastic surgeons must carefully consider the timing of administering botulinum toxin type A to patients who have recovered from COVID-19. Methods: A questionnaire survey was conducted among patients who had contracted and recovered from SARS-CoV-2 within a month. The survey aimed to investigate various indicators in patients who had received botulinum toxin A injections at the same site before and after their infection, including pain scores and allergic reactions and the occurrence of complications. Results: The pain scores of patients who contracted SARS-CoV-2 infection between 14-21 days post-infection exhibited significant variation from previous injections. However, patients who contracted the infection between 22-28 days post-infection did not exhibit significant variation from previous injections. Furthermore, the incidence of allergic reactions and complications following botulinum toxin injection within one month after contracting the infection did not significantly differ from that observed prior to infection. Conclusion: Administering botulinum toxin type A three weeks after COVID-19 recovery is a justifiable and comparatively secure approach.

Periocular methotrexate versus periocular triamcinolone injections for active thyroid-associated orbitopathy: a randomized clinical trial.

PURPOSE: To assess the efficacy and safety of periocular injections of methotrexate versus triamcinolone in the management of active thyroid-associated orbitopathy. STUDY DESIGN: Prospective, double-masked, randomized clinical trial. METHODS: Participants with bilateral active, moderate-to-severe thyroid-associated orbitopathy were randomly assigned to receive three periocular injections of 7.5 mg methotrexate in one orbit and three periocular injections of 20 mg triamcinolone in the contralateral orbit. RESULTS: Among the enrolled 25 patients, 18 patients completed the study. A statistically significant reduction of the mean clinical activity score was detected in both arms (from 5.2 ± 0.89 at baseline to 0.9 ± 1.7 at study endpoint, p-value < 0.001 in the methotrexate arm, and from 5.1 ± 0.9 at baseline to 1 ± 1.7 at study endpoint, p-value < 0.001 in the triamcinolone arm), mean proptosis also decreased in both arms (from 25.2 ± 3.4 mm at baseline to 23.8 ± 3.7 mm at study endpoint, p-value = 0.01 in the methotrexate arm, and from 24.2 ± 3.06 mm at baseline to 23.2 ± 3.3 mm at study endpoint, p-value = 0.049 in the triamcinolone arm). Lid aperture and soft tissue signs improved significantly in both arms in comparison to baseline. A statistically significant reduction in the intraocular pressure was observed in the methotrexate arm but not in the triamcinolone arm. 88.9% of patients in both arms were overall responders at 6 months. There was no significant difference in mean CAS, proptosis, lid aperture or rate of responders between the two arms at any visit. Both drugs were found to be safe with minimal local and systemic complications. CONCLUSION: Periocular injections of methotrexate represent an effective and safe alternative option for the management of active, moderate-to-severe thyroid-associated orbitopathy. Although no serious complications occurred during the 6-month follow-up, the possibility of late complications such as orbital fat atrophy cannot be ruled out.

Displacement of Submacular Hemorrhage With Vitrectomy Combined With Subretinal Balanced Salt Solution and Air.

PURPOSE: To describe a technique of displacement of submacular hemorrhage (SMH) using subretinal injection of balanced salt solution and filtered air. METHODS: Patients presenting within 2 weeks of massive SMH (>4 disk diameter) were prospectively included. All patients underwent 25-gauge pars plana vitrectomy, posterior vitreous detachment, injection of subretinal balanced salt solution and filtered air followed by partial fluid air exchange, 20% sulfur hexafluoride tamponade, and heads-up positioning postoperatively. Degree of displacement of SMH was assessed at 1 month and change in best-corrected visual acuity was assessed at 3 months. RESULTS: Ten patients with massive SMH who underwent the aforementioned procedure were included. Complete displacement of bleed from the macula was achieved in nine (90%) of 10 eyes at 1 month. There was significant improvement in best-corrected visual acuity from baseline at 1 month ( P = 0.015) and 3 months ( P = 0.043). CONCLUSION: Pars plana vitrectomy with injection of subretinal balanced salt solution and filtered air was well-tolerated and efficacious in displacing large and thick SMH in patients operated within 2 weeks of onset of symptoms.

Modified-dropless protocol (nil intraocular) for micro-incision vitrectomy surgery (MIVS): a retrospective pilot study.

BACKGROUND: Perioperative infection and inflammation prophylaxis after ocular surgery has evolved over the years along with improvements in surgical equipment and a growing interest in alternatives to the standard topical eye drops. The purpose of this study is to evaluate the outcomes of a novel, modified-dropless protocol for 23-gauge (23-G), 25-gauge (25-G) and 27-gauge (27-G) micro-incision vitrectomy surgery (MIVS) that omits any intraocular injections of antibiotics or steroids. METHODS: This Institutional Review Board-approved, single-surgeon retrospective study reviewed MIVS post-surgical outcomes in patients who received a modified-dropless protocol from February 2020 to March 2021. A total of 158 charts were reviewed, of which 150 eyes met the eligibility criteria. After each case, patients were administered a 0.5 cc subconjunctival injection of a 1:1 Cefazolin (50 mg/cc):Dexamethasone (10 mg/cc) in the inferior fornix and 0.5 cc of posterior Sub-Tenon's Kenalog (STK). No intravitreal injections were administered, and no pre- or postoperative antibiotic or steroid eye drops were prescribed. For patients allergic to penicillin, separate subconjunctival injections of 0.25 cc each of Vancomycin (10 mg/cc) and Dexamethasone (10 mg/cc) were administered. The primary safety parameter was postoperative cases of endophthalmitis. Secondary endpoints consisted of Best-Corrected Distance Visual Acuity (BCVA), intraocular pressure (IOP), and postoperative complications (retinal detachments, inflammation, need for additional surgery) within three months of surgery. Statistical analysis was performed using chi-square (χ²) tests for categorical values, and a Student's t-test to compare continuous outcomes. RESULTS: The majority of surgeries (96%) were performed with the 27G MIVS platform. There were no cases of postoperative endophthalmitis. Mean logMAR BCVA improved from 0.71 (± 0.67) to 0.61 (± 0.60) post-operatively (p = 0.02). Excluding patients who had silicone oil tamponade, postoperative BCVA improved from 0.67 (± 0.66) to 0.54 (± 0.55) (p = 0.003). Mean IOP increased from 14.6 (± 3.8) to 15.3 (± 4.1) (p = 0.05). Ten patients required further medication therapy for an increase in IOP, one had inflammatory signs, and 14 required a second surgical intervention mostly due to recurrences of initial surgical indication. CONCLUSION: A modified-dropless postoperative protocol involving subconjunctival and posterior sub-Tenon's injections only may be a safe and convenient alternative to topical eye drops for patients undergoing MIVS, but additional and larger studies are needed.

Recent advances and future prospects: Current status and challenges of the intraocular injection of drugs for vitreoretinal diseases.

Effective drug therapy for vitreoretinal disease is a major challenge in the field of ophthalmology; various protective systems, including anatomical and physiological barriers, complicate drug delivery to precise targets. However, as the eye is a closed cavity, it is an ideal target for local administration. Various types of drug delivery systems have been investigated that take advantage of this aspect of the eye, enhancing ocular permeability and optimizing local drug concentrations. Many drugs, mainly anti-VEGF drugs, have been evaluated in clinical trials and have provided clinical benefit to many patients. In the near future, innovative drug delivery systems will be developed to avoid frequent intravitreal administration of drugs and maintain effective drug concentrations for a long period of time. Here, we review the published literature on various drugs and administration routes and current clinical applications. Recent advances in drug delivery systems are discussed along with future prospects.

Effects of the periocular botulinum toxin on the ocular surface and anterior chamber: a prospective study in patients with hemifacial spasm and blepharospasm.

PURPOSE: To analyze using Pentacam®, the corneal and anterior chamber changes following periocular botulinum toxin injection in patients with facial dystonia. METHODS: Prospective study that included patients with facial dystonia that were going to receive a periocular botulinum toxin injection for the first time or six months or more after the previous injection. A Pentacam® examination was carried out in all patients before and 4 weeks after the injection. RESULTS: Thirty-one eyes were included. Twenty-two had a diagnosis of blepharospasm and nine of hemifacial spasm. Analysis of corneal and anterior chamber parameters revealed a significant decrease in iridocorneal angle after botulinum toxin injection (from 35 ± 10º to 33.8 ± 9.7º, p = 0.022). No other corneal or anterior chamber parameters changed significantly after the injection. CONCLUSIONS: Periocular botulinum toxin injection causes narrowing of the iridocorneal angle.

A novel recombinant human microplasminogen induced complete posterior vitreous detachment without morphological change of retina in juvenile rabbits.

Vitreomacular traction syndrome results from persistent vitreoretinal adhesions in the setting of partial posterior vitreous detachment (PVD). Vitrectomy and reattachment of retina is an effective therapeutic approach. The adhesion between vitreous cortex and internal limiting membrane (ILM) of the retina is stronger in youth, which brings difficulties to induce PVD in vitrectomy. Several clinical investigations demonstrated that intravitreous injection of plasmin before vitrectomy could reduce the risk of detachment. In our study, a novel recombinant human microplasminogen (rhµPlg) was expressed by Pichia pastoris. Molecular docking showed that the binding of rhµPlg with tissue plasminogen activator (t-PA) was similar to plasminogen, suggesting rh µPlg could be activated by t-PA to generate microplasmin (µPlm). Moreover, rhµPlg had higher catalytic activity than plasminogen in amidolytic assays. Complete PVD was found at vitreous posterior pole of 125 µg rhµPlg-treated eyes without morphological change of retina in juvenile rabbits via intraocular injection. Our results demonstrate that rhµPlg has a potential value in the treatment of vitreoretinopathy.

In Situ Formation of Injectable Gelatin Methacryloyl (GelMA) Hydrogels for Effective Intraocular Delivery of Triamcinolone Acetonide.

A novel drug delivery system designed for intraocular injection, gelatin methacryloyl (GelMA), has attracted much attention due to its sustained-release character and low cytotoxicity. We aimed to explore the sustained drug effect of GelMA hydrogels coupled with triamcinolone acetonide (TA) after injection into the vitreous cavity. The GelMA hydrogel formulations were characterized using scanning electron microscopy, swelling measurements, biodegradation, and release studies. The biological safety effect of GelMA on human retinal pigment epithelial cells and retinal conditions was verified by in vitro and in vivo experiments. The hydrogel exhibited a low swelling ratio, resistance to enzymatic degradation, and excellent biocompatibility. The swelling properties and in vitro biodegradation characteristics were related to the gel concentration. Rapid gel formation was observed after injection, and the in vitro release study confirmed that TA-hydrogels have slower and more prolonged release kinetics than TA suspensions. In vivo fundus imaging, optical coherence tomography measurements of retinal and choroid thickness, and immunohistochemistry did not reveal any apparent abnormalities of retinal or anterior chamber angle, and ERG indicated that the hydrogel had no impact on retinal function. The GelMA hydrogel implantable intraocular device exhibited an extended duration, in situ polymerization, and support cell viability, making it an attractive, safe, and well-controlled platform for treating the posterior segment diseases of the eye.

Generating Widespread and Scalable Retinal Lesions in Adult Zebrafish by Intraocular Injection of Ouabain.

Zebrafish regenerate functional retinal neurons after injury. Regeneration takes place following photic, chemical, mechanical, surgical, or cryogenic lesions, as well as after lesions that selectively target specific neuronal cell populations. An advantage of chemical retinal lesion for studying the process of regeneration is that the lesion is topographically widespread. This results in the loss of visual function as well as a regenerative response that engages nearly all stem cells (Müller glia). Such lesions can therefore be used to further our understanding of the process and mechanisms underlying re-establishment of neuronal wiring patterns, retinal function, and visually mediated behaviors. Widespread chemical lesions also permit the quantitative analysis of gene expression throughout the retina during the period of initial damage and over the duration of regeneration, as well as the study of growth and targeting of axons of regenerated retinal ganglion cells. The neurotoxic Na+/K+ ATPase inhibitor ouabain specifically offers a further advantage over other types of chemical lesions in that it is scalable; the extent of damage can be targeted to include only inner retinal neurons, or all retinal neurons, simply by adjusting the intraocular concentration of ouabain that is used. Here we describe the procedure through which these "selective" vs. "extensive" retinal lesions can be generated.

RETINAL TOXICITY FOLLOWING PRESUMED INADVERTENT INTRAOCULAR INJECTION OF MITOMYCIN C DURING TRABECULECTOMY.

PURPOSE: To describe a case of postoperative retinal toxicity following the use of mitomycin C during a routine trabeculectomy. METHODS: Case report of a single patient who underwent complete ophthalmic examination and multimodal imaging, including color fundus photos, optical coherence tomography, fundus autofluorescence, and fluorescein angiography. The study was declared exempt by the Institutional Review Board of Northwestern University. This research followed the tenets of the Declaration of Helsinki. RESULTS: The patient developed profound vision loss and retinal damage during the postoperative course. Posterior segment findings include loss of vascular perfusion, diffuse loss of the outer, then inner, retinal layers, and subsequent total retinal detachment. CONCLUSION: Although mitomycin C is commonly used in glaucoma filtering surgeries, reports of postoperative posterior segment toxicity are rare. The etiology of postoperative toxicity in this case is probable inadvertent intraocular injection of mitomycin C.

Sigma-1 receptor agonist, (+)-pentazocine, is neuroprotective in a Brown Norway rat microbead model of glaucoma.

PURPOSE: Glaucoma is a worldwide leading cause of irreversible blindness. Standard treatments lower intraocular pressure (IOP). Novel treatments to prevent optic nerve (ON) degeneration are needed. Here, we investigate the hypothesis that sigma-1 receptor (S1R) agonist (+)-pentazocine (PTZ) is neuroprotective in a Brown Norway (BN) rat, microbead model of glaucoma. METHODS: BN rats (9-11 weeks, male and female) were treated by intraperitoneal injection, 3 times per week with (+)-PTZ (2 mg/kg) or vehicle (VEH) alone. Treatment started 1 week prior to intraocular injection of polystyrene microbeads to elevate IOP. IOP was measured 2-3 times per week. Five weeks post microbead injection, rats were euthanized. ONs were removed, then fixed and processed for 63x oil, light microscope imaging of toluidine blue stained ON cross sections. To facilitate comparison of ON morphology from VEH and (+)-PTZ treated rats with similar ocular hypertensive insults, rats were assigned to low (IOP ≤15.8 mmHg), moderate (15.8 < IOP <28.0 mmHg), and high (IOP ≥28.0 mmHg) groups based on average IOP in the microbead injected eye. Axon numbers, axon density, axonal and glial areas, axon loss, and axon size distributions of naïve, bead, and contralateral ONs were assessed using QuPath program for automated image analysis. RESULTS: (+)-PTZ treatment of BN rats protected ONs from damage caused by moderate IOP elevation. Treatment with (+)-PTZ significantly reduced axon loss and glial areas, and increased axon density and axonal areas compared to ONs from VEH treated rats with moderate IOP. (+)-PTZ-mediated neuroprotection was independent of IOP lowering effects. At average IOP ≥28.0 mmHg, (+)-PTZ treatment did not provide measurable neuroprotection. ONs from contralateral eyes exhibited subtle, complex changes in response to conditions in the bead eyes. CONCLUSIONS: S1R agonist (+)-PTZ shows promise as a neuroprotective treatment for glaucoma. Future studies to understand the complex molecular mechanisms by which (+)-PTZ provides this neuroprotection are needed.

INADVERTENT GLOBE PENETRATION AND SUBRETINAL INJECTION OF BOTULINUM TOXIN IN A PATIENT WITH OCULOCUTANEOUS ALBINISM.

PURPOSE: To present a case of localized retinal detachment and mild vitreous hemorrhage in a patient with oculocutaneous albinism after accidental intraocular injection of botulinum toxin A. METHODS: Botulinum toxin A injection was administered to a 5-year-old patient with oculocutaneous albinism with esotropia and resulted in an ocular penetration. Dilated fundus examination indicated a nasal retinal tear causing a mild vitreous hemorrhage and a localized retinal detachment. RESULTS: No treatment was required for the retinal detachment, and we observed the patient at regular intervals. On Day 1, the detachment resolved spontaneously without sequelae. On follow-up, scarring at the lesion site was detected at one month after the incidence, and the patient's vision was stable. CONCLUSION: In this instance, observation was sufficient for our patient with complete resolution of retinal detachment and no long-term complication. Botulinum toxin A did not seem toxic to intraocular tissues. However, intramuscular botulinum toxin A injection should be administered carefully. Oculocutaneous albinism did not seem to affect the final outcome in our case.

Alzheimer PHF-tau aggregates do not spread tau pathology to the brain via the Retino-tectal projection after intraocular injection in male mouse models.

Neurofibrillary tangles (NFT), a neuronal lesion found in Alzheimer's disease (AD), are composed of fibrillary aggregates of modified forms of tau proteins. The propagation of NFT follows neuroanatomical pathways suggesting that synaptically connected neurons could transmit tau pathology by the recruitment of normal tau in a prion-like manner. Moreover, the intracerebral injection of pathological tau from AD brains induces the seeding of normal tau in mouse brain. Creutzfeldt-Jacob disease has been transmitted after ocular transplants of cornea or sclera and the scrapie agent can spread across the retino-tectal pathway after intraocular injection of scrapie mouse brain homogenates. In AD, a tau pathology has been detected in the retina. To investigate the potential risk of tau pathology transmission during eye surgery using AD tissue material, we have analysed the development of tau pathology in the visual pathway of mice models expressing murine tau, wild-type or mutant human tau after intraocular injection of pathological tau proteins from AD brains. Although these pathological tau proteins were internalized in retinal ganglion cells, they did not induce aggregation of endogenous tau nor propagation of a tau pathology in the retino-tectal pathway after a 6-month incubation period. These results suggest that retinal ganglion cells exhibit a resistance to develop a tau pathology, and that eye surgery is not a major iatrogenic risk of transmission of tau pathology, contrary to what has been observed for transmission of infectious prions in prion diseases.

Eficacia de la hialuronidasa retrobulbar en el tratamiento de la ceguera provocada por rellenos cosméticos. Revisión sistemática / Effectiveness of retrobulbar hyaluronidase in the treatment of visual loss caused by periocular hyaluronic acid injection. A systematic review

Introducción La pérdida visual relacionada con la inyección periocular de rellenos con fines cosméticos es infrecuente pero muy grave. Como recomendaciones protocolizadas ante la pérdida visual por inyección intravascular inadvertida de ácido hialurónico se encuentran, entre otras, la inyección de hialorunidasa en el espacio retroocular. Es de esperar que, dada la creciente demanda de tratamientos de rellenos estéticos y la gran heterogeneidad de profesionales que pueden administrarlos, el número de casos y complicaciones relacionadas con estos procedimientos se incremente de manera sustancial. Objetivo Evaluar si existe evidencia científica para recomendar la inyección retroocular de hialuronidasa en el tratamiento de pérdidas visuales relacionadas con la inyección periocular de ácido hialurónico cosmético. Material y métodos Hemos realizado una búsqueda de artículos publicados en inglés y español siguiendo la declaración PRISMA sobre el uso de hialuronidasa retrobulbar para revertir la pérdida de visión producida por los rellenos de ácido hialurónico. Los artículos revisados incluyeron los casos clínicos y las investigaciones experimentales. Identificamos a un total de 13 pacientes en esta revisión siguiendo unos criterios de inclusión y exclusión definidos. Finalmente, incluimos 15 artículos en el estudio, 13 de ellos fueron casos/series de casos. Los 2artículos restantes son estudios experimentales en animales con grupo control, en los que, tras provocar una oclusión selectiva de la arteria oftálmica, se administran inyecciones seriadas de hialuronidasa retroocular con control de la función visual. Resultados De los 15 artículos incluidos en el estudio, recogimos los datos de un total de 17 pacientes que, tras inyección de ácido hialurónico facial por motivos estéticos, presentaron una disminución brusca de la visión y en los que se inyectaron dosis variables de hialuronidasa retroocular (AU)

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 2remaining 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 (AU)

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.

Voriconazole-impregnated multilayered AMT and intracorneal plus intracameral injection in recalcitrant fungal corneal ulcer.

We describe the management of a referred man in his 50s with corneal ulcer in the left eye. Slit-lamp biomicroscopy revealed an infiltrate (4.5×3.5 mm), involving full corneal thickness, corneal melt less than one-third corneal thickness and hypopyon (3.0 mm). Branched septate hypha on direct microscopy and Aspergillus flavus in Sabaraud's dextrose agar confirmed the clinical diagnosis of fungal corneal ulcer. We used natamycin 5% suspension 1 hourly, voriconazole 1% 1 hourly, gatifloxacin 0.5% three times and atropine 1% three times per day, for 2 weeks. However, there was no improvement and the corneal melt increased. We used intracameral plus intracorneal voriconazole injection with voriconazole-impregnated amniotic membrane transplant. We observed a significant decrease in conjunctival congestion, size/depth of infiltrate and hypopyon at the first week of antifungal therapy. Subsequently, at 6 weeks, corneal infiltrate had decreased and superficial corneal vascularisation appeared. Later, at 12 weeks, the patient developed corneal opacity.

Arm-to-retina time predicts visual outcome of anti-vascular endothelial growth factor treatment for macular edema due to central retinal vein occlusion.

To explore the factors associated with best-corrected visual acuity (BCVA) after anti-vascular endothelial growth factor (anti-VEGF) treatment for macular edema secondary to central retinal vein occlusion (CRVO). We retrospectively reviewed the medical charts of 22 eyes of 22 treatment-naïve patients with CRVO diagnosed between September 2014 and December 2020. They received anti-VEGF treatment and follow-up for > 12 months. Mean patient age was 64.3 years; 13 (59.1%) were men. Eyes with baseline arm-to-retina (AR) time ≥ 16 s had better BCVA at 12 months (adjusted for baseline BCVA and age; B, - 0.658; 95% confidence interval - 1.058 to - 0.257; P = 0.003), greater mean BCVA change (P = 0.006), lower frequency of residual macular edema at 12 months (P = 0.026) and recurrent and/or unresolved macular edema during 12 months (P = 0.046), and higher frequency of reduction in central retinal thickness ≥ 150 µm at 1 and 12 months (both P = 0.046). Delayed AR time was associated with a better visual outcome and macular edema improvement in CRVO after anti-VEGF treatment regardless of initial BCVA and age. Our results may help understand the pathogenesis and predict the visual prognosis of patients before anti-VEGF therapy initiation.

Bacteriostatic preserved saline for pain-free periocular injections: review.

We review evidence regarding the use of 0.9% benzyl alcohol in 0.9% sodium chloride solution for periocular injections ('preserved saline') including botulinum toxin A injections and local anaesthesia. A literature search was undertaken using search terms 'bacteriostatic saline', 'benzyl-alcohol saline', 'benzyl alcohol sodium chloride' and 'preserved saline'. Bibliographies identified further sources. There have been 62 studies published on the subject of preserved-saline since 1928. Significantly lower injection-associated pain levels for periocular/facial botulinum toxin injections reconstituted with preserved-saline rather than preservative-free saline are reported by 5 studies. Significantly lower injection-associated pain with preserved-saline diluted lidocaine and epinephrine solution for eyelid anaesthesia compared with unmodified or buffered lidocaine with epinephrine, and adequate anaesthesia, was reported by one study. Thirty-one studies have explored preserved-saline for anaesthetic and seven for bacteriostatic properties, with very low infection rates after periocular botulinum toxin injections, and reduced rates of infection in indwelling catheters when preserved saline is used to flush. A meta-analysis concluded that lidocaine-containing solutions are more effective at reducing pain from insertion of intravenous catheters. Patient-perceived pain related to periorbital injections of local anaesthesia is reduced when the anaesthetic is diluted with benzyl alcohol-preserved saline compared with other dilution or buffering options. Pain is similarly reduced for periocular botulinum toxin injections reconstituted with preserved saline compared with unpreserved saline. Benzyl-alcohol preserved-saline is inexpensive but costlier than unpreserved-saline, with minimal reported complications, particularly with periocular administration, and offers the opportunity to improve the patient experience.

Comparative Assessment of Pain during Infiltration by a Two-stage Infiltration Technique: A Double-blind Clinical Trial.

AIM: The aim of this study was to assess and compare the pain during infiltration by a modified two-stage local anesthetic infiltration technique under topical anesthesia (TA). MATERIALS AND METHODS: In this cross-over double-blind study, 30 volunteers participated, where two groups were given single-stage infiltration and the other two had two-stage infiltrations. Depending upon the infiltration technique (one- or two-stage) and the use of TA, the patients were randomly divided into four groups. Local anesthesia (LA) was administered by infiltration into the mucobuccal fold of the maxillary central incisor, and the pain perceived during the infiltration in each group was recorded. The volunteers were recalled after 24 hours to assess the tenderness at the injection site. The volunteers were recalled 2 weeks after infiltration for the subsequent groups to assess the pain for this cross-over study. RESULTS: A statistically significant difference was observed in the pain perceived when TA was used and when the infiltration was done in two stages. Regarding the pain at the site of injection after 24 hours, no significant difference was observed among the volunteers. CONCLUSION: Topical anesthesia was effective in reducing the pain of injection when compared to placebo. The pain of injection is further reduced with a two-stage infiltration technique after TA application. CLINICAL SIGNIFICANCE: Topical anesthesia can be used routinely before infiltration, and LA infiltration injections are less painful if administered in two stages.