A, B, C's of Trk Receptors and Their Ligands in Ocular Repair.

Neurotrophins are a family of closely related secreted proteins that promote differentiation, development, and survival of neurons, which include nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4. All neurotrophins signal through tropomyosin receptor kinases (TrkA, TrkB, and TrkC) which are more selective to NGF, brain-derived neurotrophic factor, and neurotrophin-3, respectively. NGF is the most studied neurotrophin in the ocular surface and a human recombinant NGF has reached clinics, having been approved to treat neurotrophic keratitis. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are less studied neurotrophins in the ocular surface, even though brain-derived neurotrophic factor is well characterized in glaucoma, retina, and neuroscience. Recently, neurotrophin analogs with panTrk activity and TrkC selectivity have shown promise as novel drugs for treating dry eye disease. In this review, we discuss the biology of the neurotrophin family, its role in corneal homeostasis, and its use in treating ocular surface diseases. There is an unmet need to investigate parenteral neurotrophins and its analogs that activate TrkB and TrkC selectively.

Intravitreal Injection of PACAP Attenuates Acute Ocular Hypertension-Induced Retinal Injury Via Anti-Apoptosis and Anti-Inflammation in Mice.

Purpose: Pituitary adenylate cyclase-activating polypeptide (PACAP) has shown potent neuroprotective effects in central nervous system and retina disorders. However, whether PACAP can attenuate retinal neurodegeneration induced by acute ocular hypertension (AOH) and the underlying mechanisms remain unknown. In this study, we aimed to investigate the effects of PACAP on the survival and function of retinal ganglion cells (RGCs), apoptosis, and inflammation in a mouse model of AOH injury. Methods: PACAP was injected into the vitreous body immediately after inducing AOH injury. Hematoxylin and eosin staining and optical coherence tomography were used to evaluate the loss of retina tissue. Pattern electroretinogram was used to evaluate the function of RGCs. TUNEL assay was used to detect apoptosis. Immunofluorescence and western blot were employed to evaluate protein expression levels. Results: PACAP treatment significantly reduced the losses of whole retina and inner retina thicknesses, Tuj1-positive RGCs, and the amplitudes of pattern electroretinograms induced by AOH injury. Additionally, PACAP treatment remarkably reduced the number of TUNEL-positive cells and inhibited the upregulation of Bim, Bax, and cleaved caspase-3 and downregulation of Bcl-xL after AOH injury. Moreover, PACAP markedly inhibited retinal reactive gliosis and vascular inflammation, as demonstrated by the downregulation of GFAP, Iba1, CD68, and CD45 in PACAP-treated mice. Furthermore, upregulated expression of NF-κB and phosphorylated NF-κB induced by AOH injury was attenuated by PACAP treatment. Conclusions: PACAP could prevent the loss of retinal tissue and improve the survival and function of RGCs. The neuroprotective effect of PACAP is probably associated with its potent anti-apoptotic and anti-inflammatory effects.

The Therapeutic Roles of Recombinant Hsp90α on Cornea Epithelial Injury.

Purpose: The purpose of this study was to explore the therapeutic role of heat shock protein 90 (Hsp90) in wound healing of injury cornea epithelium. Methods: The right eye of C57BL/6N male mice were performed the debridement wounds in the center of the cornea using an algerbrush II blade. The injured area was determined by staining the cornea with fluorescein sodium and measured with image-J. Immunoblotting, ELISA and immunochemistry were used for determining protein expression. The quantitation PCR was performed to measure mRNA expression. Results: Hsp90α is upregulated at both the mRNA and protein levels, and is secreted extracellularly into the corneal stroma and tear film during the healing process after corneal injury in mice. This upregulation is associated with activation of HSF1. Administration of recombinant exogenous Hsp90α (eHsp90α) speeds up wound healing of injured corneal epithelium. The eHsp90α binds to low-density lipoprotein (LDL)-related protein-1 (LRP-1) on the corneal epithelial cells and increases phosphorylation of AKT at S473, which is associated with proliferation and migration corneal epithelial cells in vitro or vivo. Inhibition of AKT by its inhibitor LY294002 abolishes eHsp90α-induced migration and proliferation of corneal epithelial cells. Conclusion: Hsp90α is upregulated and secreted after corneal injury and acts to promote the healing process. Recombinant Hsp90α may be a promising therapeutic drug candidate for corneal injury.

Global Current Practice Patterns for the Management of Exogenous Endophthalmitis: A Survey by the American Society of Ophthalmic Trauma.

OBJECTIVE: To investigate the global practice patterns for the management of exogenous endophthalmitis. METHODS: This cross-sectional study was conducted to assess global practice patterns for the management of exogenous endophthalmitis. An online survey comprised of questions regarding the management of exogenous endophthalmitis was distributed to institutions who are members of International Globe and Adnexal Trauma Epidemiology Study Group (IGATES) or invited affiliates of the American Society of Ophthalmic Trauma and the Asia Pacific Ophthalmic Trauma Society. Responses were gathered from August 2020 to January 2021. RESULTS: Of 42 institutions, 36 responses were received (86% response rate), of which 33 (79%) were included in the analysis. Included centers were from Asia (36%), North America (36%), South America (12%), Africa (9%), Europe (3%), and Australia (3%). Oral antibiotics were administered in 19 (58%) institutions, with moxifloxacin as the preferred agent (n = 9, 27%). The preferred method for obtaining cultures was vitreous tap (n = 25, 76%). Most institutions (n = 26, 79%) routinely administered intravitreal vancomycin and ceftazidime, while intravitreal steroids were routinely administered at 11 centers (33%). Indications for performing vitrectomy included; decreased visual acuity (n = 14, 39%); all cases of exogenous endophthalmitis (n = 4, 12%); non-response to medical therapy (n = 4, 12%); or no view of the fundus (n = 4, 12%), indicating significant variation in surgical indications. More than half (n = 17, 52%) of responding institutions routinely admitted patients with exogenous endophthalmitis to the hospital. Institutions in the United States were less likely to administer oral antibiotics (27% vs. 73%, P = .024) and to admit patients (9% vs. 73%, P < .001) compared to other countries. CONCLUSIONS: This study highlights the global variations in the management of exogenous endophthalmitis, especially as it pertains to surgical indications. Further establishment of evidence-based guidelines may be beneficial to provide more uniform guidance to optimize outcomes.

Controlled release of triamcinolone from an episcleral micro film delivery system for open-globe eye injuries and proliferative vitreoretinopathy.

Open globe trauma is the major cause for single eye blindness that stem from subsequent proliferative vitreoretinopathy (PVR). Though biomaterials and tissue engineering have significantly advanced drug delivery and management of human diseases, currently there is no effective drug formulation or device to pharmacologically mitigate PVR formation after open-globe eye trauma. This highlighted the challenge we are facing to bring the technology from bench to bedside. The current study reported an engineered episcleral drug film using biodegradable material, Poly(L-lactide)-co-poly(ɛ-caprolactone), and triamcinolone acetonide (TA) as a model drug. The film can be conveniently sized into any shape to fit the configuration of the eye globe trauma and easily installed onto the ruptured sclera during primary trauma repair surgery. The film allows therapeutic TA to slow release for at least 6 months without toxicity and demonstrated a significant benefit to reduce the odds of developing severe PVR by 5.7 times when compared with a no-drug film control on a rabbit trauma PVR model. Our results suggested this micro episcleral drug film as promising drug delivery carrier for the targeted treatment of various unwanted retinal proliferation diseases.

Traumatic hyphema in a patient with severe hemophilia A: Clinical features and management.

PURPOSE: To describe a case of traumatic hyphema in a patient with severe hemophilia A. CASE: We present a case of a 16-year-old boy with severe hemophilia A who presented to our ophthalmology department with total hyphema and elevated intraocular pressure 3 days after a history of blunt ocular trauma on his right eye. Due to the persistent intraocular pressure elevation and total hyphema despite medical intervention, an early anterior chamber washout was performed with the replacement of factor VIII preoperatively and postoperatively. Re-bleeding or any other complications were not experienced during surgery or postoperatively. At the first postoperative week, 20/20 visual acuity and a normal intraocular pressure without antiglaucoma medication was retained and remained stable during the 6-month follow-up. CONCLUSION: In such cases with hemophilia A, traumatic hyphema, and intraocular pressure elevation despite medical intervention, an early surgical clot removal under intense factor VIII replacement could be performed. In the early postoperative period, factor replacement should be resumed in order to avoid re-bleeding.

Insulina tópica en el tratamiento de úlcera corneal refractaria en un paciente no diabético: a propósito de un caso / Insulin eye drops for treating corneal ulcer in a non-diabetic patient: regarding a case

Las úlceras corneales se incluyen dentro de un grupo heterogéneo de lesiones oculares, las cuales pueden ser de gravedad variable. Cuando los pacientes no responden al tratamiento, incluyendo incluso el trasplante corneal, se crea la necesidad de explorar otras alternativas. Presentamos el caso de un paciente que sufrió una salpicadura ocular del contenido de una batería de automóvil por accidente. Esta lesión corneal, fue refractaria al tratamiento farmacológico e incluso quirúrgico. Tras cuatro años de persistencia de la úlcera corneal, se inició un tratamiento tópico con insulina 50 UI/ml. Se observó mejoría de forma evidente y actualmente el paciente ha recuperado completamente el epitelio corneal. Hoy en día, las evidencias disponibles del uso tópico de la insulina para el tratamiento de las úlceras corneales se centran en pacientes diabéticos. En los pacientes no diabéticos, la evidencia se limita a una serie de casos de úlceras neurotróficas corneales y al caso de un paciente que presentó un defecto epitelial persistente después de la resección de un neurinoma. Este caso, presenta la experiencia de uso de una formulación magistral de insulina oftálmica con eficacia y ausencia de toxicidad en un paciente no diabético con una úlcera corneal post-cáustica resistente al resto de tratamientos

Corneal ulcers are included in a heterogeneous group of eye injuries. When patients do not respond to treatment, including even corneal transplant, other alternatives need to be explored.We present a case of a patient who suffered an accidental spillage from the contents of a car battery. This corneal lesion was refractory to both surgical and pharmacological treatment. After four years of a persistent ulcer, insulin topical treatment 50 IU/mL was started. Improvement began to be observed and currently the patient has completely recovered the corneal epithelium. Nowadays, evidence of the topical insulin use for the treatment of corneal ulcers is higher in diabetic patients. In non-diabetic patients, evidence is restricted to a series of cases of neurotrophic corneal ulcers and a case report of a patient who presented a persistent epithelial defect after resection of a neurinoma. This case presents the experience of using an insulin drop formulation with effectiveness and absence of toxicity in a patient non-diabetic with a post-caustic corneal ulcer

A rare case of Colletotrichum truncatum keratitis in a young boy with complete healing after medical treatment.

Colletotrichum is a rare fungal pathogen, which is known to cause anthracnose in plants and keratitis or subcutaneous infections in humans. Among the seven Colletotrichum species reported in eye infections, truncatum species is usually virulent with poor visual prognosis even after surgical treatment. Here we report a case of Colletotrichum truncatum keratitis in a young boy with thorn injury that completely resolved with topical natamycin and voriconazole.

Fungal keratitis caused by a rare pathogen, Colletotrichum gloeosporioides, in an east coast city of China.

BACKGROUND: To report a case of fungal keratitis caused by Colletotrichum gloeosporioides in an east coast city of China, which are rare pathogens that cause fungal keratitis in humans. METHODS: A 52-year-old man whose right eye was injured by a branch of an apple tree during farm work was referred to our Hospital. He was examined by Slit-lamp and the HRT II-RCM confocal scanning microscope, thus suggesting filamentous. Orneal scrapings were acquired and then inoculated into Sabouraud medium incubated at 28°C and 37°C. In vitro antifungal susceptibility tests were performed following the CLSI M38-A2 for Filamentous Fungi. Surgical intervention was advised because the abscess in the anterior chamber of the right eye was not completely absorbed. RESULTS: The Colletotrichum gloeosporioides isolate was identified by MALDI-TOF mass spectrometry and the BLAST after DNA sequencing of the amplified internal transcribed spacer (ITS) in rRNA. The patient's eye condition is under control and the patient's vision remains at the level of light perception (LP). CONCLUSIONS: We report the rare keratitis caused by C. gloeosporioides in eastern China, which has not been published. Suddenly ocular trauma and old surgical intervention may be the risk factors associated with Colletotrichum keratitis.

TRAUMATIC MACULAR HOLE CLOSURE AND VISUAL IMPROVEMENT AFTER TOPICAL NONSTEROIDAL ANTIINFLAMMATORY DRUG TREATMENT.

PURPOSE: To report a case of pediatric traumatic macular hole that closed with visual improvement after treatment with topical ketorolac. METHODS: Retrospective case report. RESULTS: A 15-year-old girl presented with persistent left blurred vision after being hit with a soccer ball 2 months before. Visual acuity was 20/40 with a full-thickness macular hole with cystoid macular edema. After treatment with ketorolac 0.4% four times a day for a month, the hole closed with resolution of the cystoid macular edema but some remaining subretinal fluid. The ketorolac was tapered over the following month, and the subretinal fluid resolved during the subsequent months. At 10 months after initial presentation, patient's vision was 20/20 with a normal foveal contour, no subretinal fluid, and minimal ellipsoid zone disruption. CONCLUSION: Topical nonsteroidal antiinflammatory drug treatment may play a role in the resolution of traumatic macular holes with cystoid macular edema.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS IN A CASE OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO TRAUMATIC CHOROIDAL RUPTURE.

BACKGROUND/PURPOSE: To document by optical coherence tomography angiography, the onset of a choroidal neovascularization (CNV) secondary to traumatic choroidal rupture and describe its changes after an intravitreal injection of bevacizumab. METHODS: Case report. RESULTS: A 20-year-old woman presented referring vision loss after a blunt ocular trauma in her left eye. The patient underwent a complete ophthalmic examination. Best-corrected visual acuity was 20/200. Fundus examination, fluorescein angiography, indocyanine green angiography, and optical coherence tomography displayed a choroidal rupture with no evidence of CNV. Optical coherence tomography angiography showed the choroidal rupture as a line of choriocapillaris rarefaction because of the mechanical damage. Six months later, best-corrected visual acuity decreased to 20/300; optical coherence tomography angiography displayed the growth of a CNV, characterized by a tangled vascular network. After one intravitreal injection of bevacizumab, optical coherence tomography angiography documented a contraction of the CNV. CONCLUSION: Optical coherence tomography angiography is a useful imaging technique for the diagnosis and follow-up of patients with choroidal ruptures. Anti-vascular endothelial growth factor agents represent an effective therapy for the treatment of CNVs secondary to this affection.

Long-term treatment with 3, 4-methylenedioxymethamphetamine caused retina damage in C57BL/6 mice / Tratamento a longo prazo com 3, 4-metilenedioximetanfetamina causando dano na retina em camundongos C57BL/6

ABSTRACT Purpose: As a class of psychostimulant drugs, amphetamines are widely abused for their stimulant, euphoric, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Following the onset of these effects, 3,4 methylenedioxymethamphetamine produces persistent damage to dopamine and serotonin nerve terminals, resulting in long-lasting neurotoxicity. The purpose of this investigation was to assess the effects of treatment with low dose of methylenedioxymethamphetamine on retinal function of C57BL/6 mice and its underlying mechanisms. Methods: C57BL/6 mice were divided randomly into two groups (n=10): one group was treated with phosphate buffered saline by intraperitoneal injection daily; the other group was treated with 1 mg/kg methylenedioxymethamphetamine by intraperitoneal injection daily for three months. Electroretinography was used to test retinal function every month. H&E staining and terminal deoxynucleotidyl transferase assay were used to evaluate the retinal morphology and histology. Enzyme-linked immunosorbent assay assays were used to measure markers of oxidative stress and inflammatory factors. Gene and protein expression was detected by real-time PCR and western blot. Results: Three-month treatment with methylenedioxymethamphetamine induced significant retinal dysfunction via photoreceptor cell apoptosis by oxidative stress and inflammatory responses. Conclusions: These results suggest that long-term treatment with methylenedioxymethamphetamine increases inflammatory responses in photoreceptor cells resulting in retinal dysfunction in C57BL/6 mice. Thus, this investigation provides preclinical rationale for the retina damage caused by the methylenedioxymethamphetamine abuse.

RESUMO Objetivos: Como uma classe de drogas psicoesti mulantes, as anfetaminas são amplamente usadas por suas propriedades estimulantes, eufóricas e alucinógenas. Muitos desses efeitos resultam de aumentos agudos na neurotransmissão da dopamina e da serotonina. Após o início desses efeitos, a 3,4-metilenedioximetanfetamina produz danos persistentes nos terminais nervosos de dopamina e serotonina, resultando em neurotoxicidade duradoura. O objetivo desta investigação foi avaliar os efeitos do tratamento baixa dose de metilenedioximetanfetamina na função da retina em camundongos C57BL/6 e seus mecanismos subjacentes. Métodos: Camundongos C57BL/6 foram divididos aleatoriamente em dois grupos (n=10): um grupo foi tratado com solução salina tamponada de fosfato por injeção intraperitoneal diária; o outro grupo foi tratado com 1 mg/kg de metilenedioximetanfetamina por injeção intraperitoneal diária durante 3 meses. Eletroretinografia foi utilizada para testar a função da retina a cada mês. A coloração H&E e análise com deoxinucleotidil terminal transferase foram utilizados para avaliar a morfologia e histologia da retina. Testes de imunoabsorção enzimática foram utilizados para medir marcadores de estresse oxidativo e fatores inflamatórios. A expressão de genes e proteínas foi detectada por PCR em tempo real e western blot. Resultados: O tratamento de três meses com metilenedioximetanfetamina induziu disfunção de retina significativa por apoptose de células fotorreceptoras por estresse oxidativo e resposta inflamatória. Conclusões: Estes resultados sugerem que o tratamento a longo prazo com metilenedioximetanfetamina aumenta as respostas inflamatórias em células fotorreceptoras, resultando em disfunção de retina em camundongos C57BL/6. Assim, a investigação foence uma justificação pré-clínica para os danos na retina causados pelo abuso de metilenedioximetanfetamina.

Long-term treatment with 3,4-methylenedioxymethamphetamine caused retina damage in C57BL/6 mice.

PURPOSE: As a class of psychostimulant drugs, amphetamines are widely abused for their stimulant, euphoric, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Following the onset of these effects, 3,4 methylenedioxymethamphetamine produces persistent damage to dopamine and serotonin nerve terminals, resulting in long-lasting neurotoxicity. The purpose of this investigation was to assess the effects of treatment with low dose of methylenedioxymethamphetamine on retinal function of C57BL/6 mice and its underlying mechanisms. METHODS: C57BL/6 mice were divided randomly into two groups (n=10): one group was treated with phosphate buffered saline by intraperitoneal injection daily; the other group was treated with 1 mg/kg methylenedioxymethamphetamine by intraperitoneal injection daily for three months. Electroretinography was used to test retinal function every month. H&E staining and terminal deoxynucleotidyl transferase assay were used to evaluate the retinal morphology and histology. Enzyme-linked immunosorbent assay assays were used to measure markers of oxidative stress and inflammatory factors. Gene and protein expression was detected by real-time PCR and western blot. RESULTS: Three-month treatment with methylenedioxymethamphetamine induced significant retinal dysfunction via photoreceptor cell apoptosis by oxidative stress and inflammatory responses. CONCLUSIONS: These results suggest that long-term treatment with methylenedioxymethamphetamine increases inflammatory responses in photoreceptor cells resulting in retinal dysfunction in C57BL/6 mice. Thus, this investigation provides preclinical rationale for the retina damage caused by the methylenedioxymethamphetamine abuse.

Evaluation of Traumatic Uveitis in the Emergency Department.

Eye trauma is a common presenting complaint in the emergency department. Correctly identifying the underlying pathology in eye trauma is critical to developing appropriate treatment plans that reduce the risk of long-term sequelae, and reduce or eliminate threats to vision. The clinical evaluation and diagnosis can be complex, and the presentation of serious eye conditions can be similar to that of more benign conditions. This article focuses on traumatic uveitis. It addresses the elements of history and examination that should suggest uveitis as the cause of pain and redness following trauma to the eye. It also outlines specific findings that can help differentiate uveitis from other causes of eye pain and redness following trauma. Included is a brief description of the pathophysiology of uveitis and the mechanism by which this inflammatory condition can result in loss of vision. Discussion includes recommended treatment. It offers a straightforward approach to making the diagnosis of traumatic uveitis.

Therapeutic effects of proanthocyanidin and coenzyme Q10 on nitrogen mustard-induced ocular injury.

PURPOSE: Nitrogen mustard (NM) is a devastating casualty agent in chemical warfare. There is no effective antidote to treat NM-induced ocular injury. We aimed to assess the effects of proanthocyanidin (PAC) and coenzyme Q10 (CoQ10) on NM-induced ocular injury. METHODS: Eighteen male rats were divided into the following 4 groups: NM, NM + PAC, NM + CoQ10, and control. The 3 NM groups received a single dose of NM (0.02 mg/µL) on the right eye to induce ocular injury. The control group received saline only. Thirty minutes after the application of NM, the NM + PAC group received PAC (100 mg/kg) via gastric gavage, while the NM + CoQ10 group received CoQ10 (10 mg/kg) via intraperitoneal injection. PAC and CoQ10 were administered once a day for 5 consecutive days. The rats were then sacrificed. Macroscopic images of the eyes were examined and eye tissues were collected for histology. RESULTS: The treatment groups were compared to the control group with regard to both corneal opacity and lid injury scores. The findings were not significantly different for both the NM + PAC and NM + CoQ10 groups. In both the NM + PAC and NM + CoQ10 groups, the histological changes seen in the NM group demonstrated improvement. CONCLUSIONS: Our results indicate that PAC and CoQ10 treatments have therapeutic effects on NM-induced ocular injury in a rat model. PAC and CoQ10 may be novel options in patients with NM-induced ocular injury.