Lirentelimab for severe and chronic forms of allergic conjunctivitis.

BACKGROUND: Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells. OBJECTIVE: We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study. METHODS: Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed. RESULTS: Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (-61%; 95% CI, -75% to -48%) and Ocular Symptom Scores (-53%; 95% CI, -76% to -31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with -55% (95% CI, -78% to -31%), -50% (95% CI, -82% to -19%), and -63% (95% CI, -87% and -38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions. CONCLUSIONS: Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.

Late Onset Uveitis-glaucoma-hyphema Syndrome with Out-the-bag Placement of Intraocular Lens.

Aim: To report a case of uveitis-glaucoma-hyphema (UGH) syndrome secondary to a tilted toric intraocular lens (IOL). Background: Over the past few decades, upgrades in lens design, surgical techniques, and posterior chamber IOLs have drastically decreased the incidence of UGH syndrome. We present a rare case of UGH syndrome developing 2 years after a seemingly uneventful cataract surgery and its subsequent management. Case description: A 69-year-old female presented with episodes of sudden visual disturbance in her right eye 2 years after a seemingly uneventful cataract surgery with placement of a toric IOL. Workup included ultrasound biomicroscopy (UBM), which revealed a tilted IOL and confirmed haptic-induced iris transillumination defects consistent with the diagnosis of UGH syndrome. The patient underwent surgical repositioning of the IOL, which led to the resolution of UGH. Conclusion: Uuveitis-glaucoma-hyphema developed from a tilted toric IOL inducing posterior iris chaffing. Careful examination and UBM revealed the IOL and haptic out of the bag position, which was critical in determining the underlying UGH mechanism. The surgical intervention led to the resolution of UGH syndrome. Clinical significance: In patients with a history of uneventful cataract surgery who develop UGH-like symptoms, continued examination of implant orientation and haptic position is critical in preventing the need for future procedures. How to cite this article: Zhou B, Bekerman VP, Chu DS, et al. Late Onset Uveitis-glaucoma-hyphema Syndrome with Out-the-bag Placement of Intraocular Lens. J Curr Glaucoma Pract 2022;16(3):205-207.

Repository Corticotropin Injection as an Alternative Treatment for Refractory Ocular Mucous Membrane Pemphigoid.

PURPOSE: The purpose of this study was to report the clinical course and outcome of patients with refractory ocular mucous membrane pemphigoid (MMP) treated by repository corticotropin injection (RCI). METHODS: Patients with biopsy-proven ocular MMP treated with RCI from 3 tertiary medical centers were evaluated. Medical records between January 2013 and January 2021 were reviewed and deidentified to retrieve relevant disease-related data. Primary outcome measures included conjunctival inflammatory activity, change in Foster clinical conjunctival scarring staging after RCI treatment, and the development of ocular and systemic complications. RESULTS: Included were 15 patients (10 women and 5 men; 36-95 yrs of age) with a mean follow-up of 4.5 years. Most of the patients (80%) had Foster stage 3 at presentation, and all patients had active MMP. Each patient had failed to respond to at least 1 immunomodulatory drug during the follow-up, and 9 (60%) patients had treatment failure of at least 2 other agents before the use of RCI. The mean duration of RCI treatment was 21 months (range, 3-54 mo). Foster stage did not change in any of the 15 patients at the last follow-up. Nine patients continued RCI therapy at the last follow-up, and in all of them, the disease activity of MMP was well controlled. No serious adverse events because of RCI were documented during the follow-up in any treated patient. CONCLUSIONS: RCI may serve as an alternative or an adjunctive treatment in patients with severe and refractory ocular MMP. Treatment with RCI seems to be safe and well-tolerated.

A Novel Virtual Wet Lab-Using a Smartphone Camera Adapter and a Video Conference Platform to Provide Real-Time Surgical Instruction.

PURPOSE: Proctored surgical instruction has traditionally been taught through in-person interactions in either the operating room or an improvised wet lab. Because of the COVID-19 pandemic, live in-person instruction was not feasible owing to social distancing protocols, so a virtual wet lab (VWL) was proposed and implemented. The purpose of this article is to describe our experience with a VWL as a Descemet membrane endothelial keratoplasty (DMEK) skills-transfer course. This is the first time that a VWL environment has been described for the instruction of ophthalmic surgery. METHODS: Thirteen participant surgeons took part in VWLs designed for DMEK skills transfer in September and October 2020. A smartphone camera adapter and a video conference software platform were the unique media for the VWL. After a didactic session, participants were divided into breakout rooms where their surgical scope view was broadcast live, allowing instructors to virtually proctor their participants in real time. Participants were surveyed to assess their satisfaction with the course. RESULTS: All (100%) participants successfully injected and unfolded their DMEK grafts. Ten of the 13 participants completed the survey. Respondents rated the experience highly favorably. CONCLUSIONS: With the use of readily available technology, VWLs can be successfully implemented in lieu of in-person skills-transfer courses. Further development catering to the needs of the participant might allow VWLs to serve as a viable option of surgical education, currently limited by geographical and social distancing boundaries.

Cicatrizing conjunctivitis as an uncommon manifestation of primary Sjögren's syndrome.

PURPOSE: To report occurrence of cicatrizing conjunctivitis as an extraglandular ocular manifestation of primary Sjögren's syndrome (SS). METHODS: Medical charts of all patients with SS evaluated at two tertiary ophthalmological referral centers were reviewed. Patients who demonstrated clinical findings of cicatrizing conjunctivitis were included in this review. Patient and disease-related data including ocular complications, therapies and outcomes were collected. RESULTS: Eight patients with a diagnosisis of SS were noted to have cicatrizing conjunctivitis findings over a period of 11 years (between 2009 and 2020). Mean age of patients was 79. All patients had a negative immunoreactant deposition in conjunctival biopsy. Mean follow-up time was 6 years (range, 18-197 months). Three patients had progression of conjunctival scarring. Worsening of vision occurred in 4 patients due to corneal complications, including ulceration, perforation and scarring. CONCLUSIONS: SS is an under-recognized etiology of severe progressive cicatrizing conjunctivitis that can lead to ocular morbidity and loss of vision without appropriate management.

Use of Adrenocorticotropic Hormone in Ophthalmology.

The ability of the adrenocorticotropic hormone (ACTH) to induce steroidogenesis and upregulate anti-inflammatory processes has long been known. More recently, however, extrasteroidal mechanisms, through which ACTH exerts anti-inflammatory processes, have been described. This has renewed hope that ACTH can combat inflammatory conditions even when resistant to steroids. This review article summarizes the literature on the use of ACTH in ocular disease. Unfortunately, much of the data regarding the clinical utility of ACTH are outdated, with many studies published in the 1950s and 1960s. Many of these older studies are inconsistent or incomplete with their reporting, making it difficult to ascertain the meaning of the outcomes. Despite the limitations, 2 important trends are evident. First, when used to treat an inflammatory disease, ACTH can be effective at decreasing or eliminating ocular inflammation, even in a refractory disease resistant to multiple treatment modalities. Second, adverse effects of ACTH are rare and are most likely to be reported with relatively high doses of ACTH therapy. Taken as a whole, these studies offer initial promising data that ACTH may be a safe and effective alternative in refractory ocular inflammatory disease. However, they highlight an important lack of prospective data to more rigorously understand the true safety and efficacy of this therapy.

Refractive surgery for the patient with autoimmune diseases.

PURPOSE OF REVIEW: Autoimmune and immune-mediated diseases are considered contraindications for laser refractive surgeries according to the US Food and Drug Administration's guideline. This guideline, however, is based on limited case reports or complications reported during other intraocular procedures. There have been only a handful of new clinical studies that evaluate the efficacy and safety of refractive surgery in this specific patient population. The aim of this article is to review currently available research and offer updated recommendations for the evaluation and management of laser refractive surgery (LRS) in patients with autoimmune diseases. RECENT FINDINGS: More recent retrospective studies have reported good refractive outcomes in patients with well controlled autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, seronegative spondyloarthropathy, among others. No severe sight-threatening complications have been reported in these reports. Although postoperative complications occur, the risk of refractive surgery is comparable with those without autoimmune diseases. SUMMARY: With the exception of primary Sjogren's syndrome, patients with autoimmune diseases may be good candidates for LRS if diseases are well controlled and have minimal ophthalmic manifestation. Patients should be made aware of the potential surgical complications and be informed of the currently available data. More multicenter and larger prospective studies are needed to compare the refractive outcomes and surgical complications in patients with and without autoimmune diseases. This will help patients make better informed medical decisions.

Certolizumab pegol - Tumor necrosis factor inhibitor for refractory uveitis.

PURPOSE: The purpose of our study is to report our experience with the use of certolizumab pegol in patients with refractory non-infectious uveitis. OBSERVATIONS: We present a case series of three patients with non-infectious uveitis, treated with twice-monthly subcutaneous certolizumab pegol. All of our patients had different types of uveitis and different underlying etiologies. All of our patients had previously failed various immunomodulatory therapies and/or were intolerant to at least one tumor necrosis factor (TNF) inhibitor agent. Following initiation of therapy with certolizumab pegol, all three patients showed significant clinical improvement of their ocular inflammation. No adverse events from treatment with certolizumab pegol were observed. CONCLUSIONS AND IMPORTANCE AND IMPORTANCE: We observed positive outcomes using the TNF inhibitor certolizumab pegol for the treatment of patients with refractory, non-infectious uveitis, in whom therapy with other TNF inhibitors was inadequate or in which there were tolerance issues. Patients who have failed other TNF inhibitors may benefit from treatment with certolizumab pegol.

Adrenocorticotropic hormone analogue as novel treatment regimen in ocular cicatricial pemphigoid.

PURPOSE: To report the clinical outcome of a patient with ocular cicatricial pemphigoid, treated with adrenocorticotropic hormone gel. OBSERVATIONS: A 75-year-old female with a biopsy proven ocular cicatricial pemphigoid (OCP) presented with bilateral conjunctival inflammation, fornix shortening, subepithelial fibrosis and corneal scarring. The patient was previously treated with topical steroids, topical cyclosporine and lubricating drops, and had undergone several amniotic membrane transplants due to recurrent corneal erosions. Once OCP diagnosis was established, the patient was started on oral corticosteroids (60 mg daily). In order to wean the patient off from systemic steroids, other immunomodulatory agents had been tried, including mycophenolate mofetil (1000 mg twice daily) and methotrexate (up to 25 mg weekly). However, none of these agents adequately controlled the ocular surface inflammation, and the patient experienced bilateral progressive cicatrization and corneal decompensation, as well as the development of side effects from the systemic corticosteroids, methotrexate and mycophenolate mofetil therapies. Treatment with twice weekly subcutaneous adrenocorticotropic hormone (ACTH) gel was initiated, along with tapering of systemic corticosteroids. During the 19 months treatment period, the patient demonstrated significant improvement in the ocular surface inflammation, visual acuity was stable and no significant adverse effects were observed. Systemic corticosteroids dosage was successfully reduced from 10 mg/day to none at last follow up. CONCLUSIONS AND IMPORTANCE: ACTH gel has shown to be an effective and safe treatment option for chronic, refractory and progressive ocular inflammatory disease. To the best of our knowledge, this is the first case report of a patient with OCP, treated successfully with ACTH gel. This case report may encourage ophthalmologists to employ ACTH gel in the management of OCP.

INFECTIOUS KERATITIS-ASSOCIATED ENDOPHTHALMITIS: A 14-Year Study.

PURPOSE: To describe the demographics, characteristics, management, and outcomes of eyes with endophthalmitis related to infectious keratitis. METHODS: Retrospective chart review of all patients treated for infectious keratitis-associated infectious endophthalmitis between 2001 and 2014 at University Hospital, Rutgers New Jersey Medical School. RESULTS: Thirty-eight cases with infectious keratitis-associated infectious endophthalmitis were identified (21 men [55%], mean age: 66.2 ± 20.7 years), with average time from the beginning of ulcer symptoms to endophthalmitis of 11.0 days. Associated systemic conditions (diabetes, HIV, immunosuppressive therapy, cirrhosis, or dementia) were present in 57.9%; 60.5% had previous intraocular surgery. Etiology showed gram-positive bacteria in 14 cases (36.9%), gram-negative bacteria in 7 (18.4%), fungi in 4 (10.5%), and no growth/unknown in 12 (31.6%). Nineteen cases (50%) presented with no light perception and were primarily enucleated. The remaining 19 eyes each received intravitreal antibiotics (mean: 1.5 injections); 8 (42.0%) underwent pars plans vitrectomy with vitreous biopsy, whereas 5 (26.3%) received emergency corneal transplantation. Final visual acuity was no light perception in 6 eyes (3 secondarily enucleated), light perception in 2, hand motion in 7, counting fingers in 2, and ≥20/50 in 2. CONCLUSION: Our study of 38 eyes with infectious keratitis-associated infectious endophthalmitis revealed generally poor visual outcomes and a high rate of systemic conditions and previous intraocular surgery.

COMPREHENSIVE REVIEW OF GOLF-RELATED OCULAR INJURIES.

PURPOSE: The authors aimed to analyze the causes and outcomes of golf-related ocular injuries in this retrospective meta-analysis, literature review, and original case series. METHODS: Forty-one articles identified by PubMed search resulted in 11 included studies yielding 102 subjects. Included articles described all ocular golf injuries that presented to an institution during a determined period. Eight factors were analyzed: age, sex, location and mechanism of injury, protective eyewear use, resulting open-globe injury, resulting enucleation, and visual acuity changes. RESULTS: No subjects wore adequate protective eyewear. Significantly more subjects were injured by golf balls (72%) than golf clubs (27%) or foreign body (1%) (P < 0.0001). The ratio of golf ball to club injuries was significantly higher in adults (92%) than in children (23%) (P < 0.0001). Forty-seven of 93 (51%) injuries resulted in an open globe, whereas 27/82 (33%) injuries resulted in enucleation. The mean ± SD logMAR visual acuity improved by -0.641 ± 0.745 after treatment (>6 lines of improvement; P = 0.0001). CONCLUSION: Reported ocular golf injuries occur less frequently than other ocular sports injuries, but may result in devastating outcomes. Supervision of children using golf equipment should be encouraged.

Chronic Non-infectious Uveitis in Patients with Juvenile Idiopathic Arthritis.

PURPOSE: To describe clinical findings and analyze treatment evolution of chronic, non-infectious uveitis in patients with juvenile idiopathic arthritis (JIA). METHODS: A total of 82 patients (147 eyes) with JIA-related uveitis treated for ≥2 months were included (78% females; 79% bilateral uveitis; 74% anterior uveitis). Outcome measures were visual acuity (VA), inflammation control, side-effects, and surgical procedures. RESULTS: Mean ± SD age at diagnosis was 4.9 ± 3.8 years; mean ± SD follow-up time was 8.7 ± 7.8 years. Mean VA did not significantly change throughout the study. Three (2%) eyes resulted in no light perception (NLP) vision. Thirty (37%) patients underwent 69 procedures. In total, 41 (50%) patients achieved inflammation control. TNF-α inhibitors were significantly associated with inflammation control. Seven (8.5%) patients stopped treatment due to side-effects. CONCLUSIONS: JIA is a cause of significant ocular morbidity. TNF-α inhibitor use was associated with inflammation control. Prospective, randomized, double blind clinical trials in this regard are warranted.

The Use of Ozurdex (Dexamethasone Intravitreal Implant) During Anterior Segment Surgery in Patients with Chronic Recurrent Uveitis.

PURPOSE: To describe the outcomes of concurrent Ozurdex implantation during anterior segment surgery in patients with chronic recurrent uveitis. METHODS: Retrospective chart review. Data recorded from preoperative and 1-, 3-, and 6-month postoperative visits included visual acuity, intraocular pressure (IOP), medications, and clinical examination findings of inflammation. RESULTS: Twelve patients (12 eyes) with chronic, recurrent noninfectious uveitis undergoing cataract extraction (n=9) or intraocular lens (IOL) explantation (n=3) were included. Mean duration of follow-up after Ozurdex implantation was 12.9 months. There was a significant reduction (n=10, P=0.02) in the average number of inflammation recurrences 6 months before surgery compared to 6 months after surgery with Ozurdex in affected eyes. IOP remained stable in the postoperative period. One patient undergoing anterior chamber IOL (ACIOL) explantation experienced migration of Ozurdex into the anterior chamber resulting in corneal edema that resolved after 1 month. CONCLUSIONS: Ozurdex safely and effectively controlled postoperative inflammation in eyes with chronic recurrent uveitis when concurrently implanted during anterior segment surgery in our patients. Caution should be exercised in cases of IOL explantation, as Ozurdex use is now contraindicated in eyes with posterior capsule rupture and ACIOLs.

Multivalent display of pendant pro-apoptotic peptides increases cytotoxic activity.

Several cationic antimicrobial peptides have been investigated as potential anti-cancer drugs due to their demonstrated selective toxicity towards cancer cells relative to normal cells. For example, intracellular delivery of KLA, a pro-apoptotic peptide, results in toxicity against a variety of cancer cell lines; however, the relatively low activity and small size lead to rapid renal excretion when applied in vivo, limiting its therapeutic potential. In this work, apoptotic peptide-polymer hybrid materials were developed to increase apoptotic peptide activity via multivalent display. Multivalent peptide materials were prepared with comb-like structure by RAFT copolymerization of peptide macromonomers with N-(2-hydroxypropyl) methacrylamide (HPMA). Polymers displayed a GKRK peptide sequence for targeting p32, a protein often overexpressed on the surface of cancer cells, either fused with or as a comonomer to a KLA macromonomer. In three tested cancer cell lines, apoptotic polymers were significantly more cytotoxic than free peptides as evidenced by an order of magnitude decrease in IC50 values for the polymers compared to free peptide. The uptake efficiency and intracellular trafficking of one polymer construct was determined by radiolabeling and subcellular fractionation. Despite their more potent cytotoxic profile, polymeric KLA constructs have poor cellular uptake efficiency (<1%). A significant fraction (20%) of internalized constructs localize with intact mitochondrial fractions. In an effort to increase cellular uptake, polymer amines were converted to guanidines by reaction with O-methylisourea. Guanidinylated polymers disrupted function of isolated mitochondria more than their lysine-based analogs, but overall toxicity was decreased, likely due to inefficient mitochondrial trafficking. Thus, while multivalent KLA polymers are more potent than KLA peptides, these materials can be substantially improved by designing next generation materials with improved cellular internalization and mitochondrial targeting efficiency.

Lacrimal gland uptake of (67)Ga-gallium citrate correlates with biopsy results in patients with suspected sarcoidosis.

PURPOSE: To investigate whether lacrimal gland uptake on (67)Ga-gallium citrate scintigraphy correlates with histopathologic evidence of sarcoidosis. METHODS: A retrospective, pilot study of 31 patients with suspected sarcoidosis who underwent gallium scintigraphy and lacrimal gland biopsy. Lacrimal gland gallium uptake was assessed by subjective visual scoring (SVS) and lacrimal uptake ratio (LUR). RESULTS: Eleven (36%) patients had lacrimal gland biopsies containing noncaseating granulomas. A statistically significant correlation was found between lacrimal gland gallium uptake and biopsy positivity using SVS (p = 0.03) or LUR (p = 0.01). Using SVS, biopsy positivity rate increased from 0 to 50% in patients with mild to intense uptake. Using LUR, biopsy positivity rate increased linearly as the ratio increased from 13% (LUR < 4) to 100% (LUR > 8). CONCLUSIONS: Lacrimal biopsy positivity rate significantly correlated with gallium uptake on scintigraphy. Both SVS and LUR methods appear to correlate with histologic results and may potentially aid in patient selection for biopsy.

Treatment of chronic, noninfectious, nonnecrotizing scleritis with tumor necrosis factor alpha inhibitors.

PURPOSE: To evaluate the use of TNF-alpha inhibitors for non-infectious, non-necrotizing scleritis. METHODS: We conducted a retrospective chart review of patients with non-infectious, non-necrotizing scleritis treated at our institutions from 2002 to 2012. RESULTS: Seventeen patients (26 eyes) were included. Ten patients were started on infliximab and seven on adalimumab; five patients were treated with both TNF-alpha inhibitors on separate occasions. All patients had an associated autoimmune disease. Control of active inflammation for at least 2 months was achieved in 15 (88%) of 17 patients. Seven out of eight patients successfully tapered concurrent corticosteroid use. Only one patient discontinued TNF-alpha inhibitor use due to an allergic reaction. CONCLUSIONS: TNF-alpha inhibitors appear to have a role in managing non-infectious, non-necrotizing scleritis refractory to initial therapy, mainly by reducing inflammation and decreasing concurrent CS use.

Optimization of Tet1 ligand density in HPMA-co-oligolysine copolymers for targeted neuronal gene delivery.

Targeted gene delivery vectors can enhance cellular specificity and transfection efficiency. We demonstrated previously that conjugation of Tet1, a peptide that binds to the GT1b ganglioside, to polyethylenimine results in preferential transfection of neural progenitor cells in vivo. In this work, we investigate the effect of Tet1 ligand density on gene delivery to neuron-like, differentiated PC-12 cells. A series of statistical, cationic peptide-based polymers containing various amounts (1-5 mol%) of Tet1 were synthesized via one-pot reversible addition-fragmentation chain transfer (RAFT) polymerization by copolymerization of Tet1 and oligo-l-lysine macromonomers with N-(2-hydroxypropyl)methacrylamide (HPMA). When complexed with plasmid DNA, the resulting panel of Tet1-functionalized polymers formed particles with similar particle size as particles formed with untargeted HPMA-oligolysine copolymers. The highest cellular uptake in neuron-like differentiated PC-12 cells was observed using polymers with intermediate Tet1 peptide incorporation. Compared to untargeted polymers, polymers with optimal incorporation of Tet1 increased gene delivery to neuron-like PC-12 cells by over an order of magnitude but had no effect compared to control polymers in transfecting NIH/3T3 control cells.

Melittin-grafted HPMA-oligolysine based copolymers for gene delivery.

Non-viral gene delivery systems capable of transfecting cells in the brain are critical in realizing the potential impact of nucleic acid therapeutics for diseases of the central nervous system. In this study, the membrane-lytic peptide melittin was incorporated into block copolymers synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The first block, designed for melittin conjugation, was composed of N-(2-hydroxypropyl)methacrylamide (HPMA) and pyridyl disulfide methacrylamide (PDSMA) and the second block, designed for DNA binding, was composed of oligo-l-lysine (K10) and HPMA. Melittin modified with cysteine at the C-terminus was conjugated to the polymers through the pyridyl disulfide pendent groups via disulfide exchange. The resulting pHgMelbHK10 copolymers are more membrane-lytic than melittin-free control polymers, and efficiently condensed plasmid DNA into salt-stable particles (~100-200 nm). The melittin-modified polymers transfected both HeLa and neuron-like PC-12 cells more efficiently than melittin-free polymers although toxicity associated with the melittin peptide was observed. Optimized formulations containing the luciferase reporter gene were delivered to mouse brain by intraventricular brain injections. Melittin-containing polyplexes produced about 35-fold higher luciferase activity in the brain compared to polyplexes without melittin. Thus, the melittin-containing block copolymers described in this work are promising materials for gene delivery to the brain.

Haemophilus influenza endophthalmitis after pterygium surgery.

OBJECTIVE: To describe a case of Haemophilus influenza endophthalmitis after pterygium surgery. METHOD: Retrospective case report. RESULTS: A 50-year-old Hispanic male underwent a pterygium excision with amniotic membrane graft (AMG) and 0.02% MMC. He presented 3.5 months later with severe pain, yellow-white discharge, and decreased visual acuity for several days, and conjunctival injection for 3 months. Repair of perforation with a corneal graft was performed. Intravitreal antibiotics were administered. Many ß-lactamase negative H. influenza organisms were cultured from the vitreous aspirate. The vitritis significantly improved and hypopyon resolved over the next week. The patient underwent surgery for a combined tractional and rhegmatogenous RD 9 days later. The endophthalmitis resolved; however, he developed proliferative vitreoretinopathy (PVR) with redetached retina 21 days after the initial RD repair. He underwent subsequent surgery. Six months later, AMG was performed for recurrent corneal erosion with a large epithelial defect. At last follow-up, the vision remains at hand motions, the retina is flat, there is mild corneal decompensation, the eye is soft to palpation, and there are signs of early phthisis. CONCLUSIONS: A prospective study to identify the optimal concentration and period of application for MMC, as well as patient characteristics resulting in the highest clinical benefit-to-risk ratio may be warranted.

Neuron-targeted copolymers with sheddable shielding blocks synthesized using a reducible, RAFT-ATRP double-head agent.

Adaptation of in vitro optimized polymeric gene delivery systems for in vivo use remains a significant challenge. Most in vivo applications require particles that are sterically stabilized, which significantly compromises transfection efficiency of materials shown to be effective in vitro. We present a multifunctional well-defined block copolymer that forms particles useful for cell targeting, reversible shielding, endosomal release, and DNA condensation. We show that targeted and stabilized particles retain transfection efficiencies comparable to the nonstabilized formulations. A novel, double-head agent that combines a reversible addition-fragmentation chain transfer agent and an atom transfer radical polymerization initiator through a disulfide linkage is used to synthesize a well-defined cationic block copolymer containing a hydrophilic oligoethyleneglycol and a tetraethylenepentamine-grafted polycation. This material effectively condenses plasmid DNA into salt-stable particles that deshield under intracellular reducing conditions. In vitro transfection studies show that the reversibly shielded polyplexes afford up to 10-fold higher transfection efficiencies than the analogous stably shielded polymer in four different mammalian cell lines. To compensate for reduced cell uptake caused by the hydrophilic particle shell, a neuron-targeting peptide is further conjugated to the terminus of the block copolymer. Transfection of neuron-like, differentiated PC-12 cells demonstrates that combining both targeting and deshielding in stabilized particles yields formulations that are suitable for in vivo delivery without compromising in vitro transfection efficiency and are thus promising carriers for in vivo gene delivery applications.