Pneumatic Vitreolysis using C3F8 Gas in Treatment Naive Patients with Vitreomacular Traction.

PURPOSE: Evaluation of the effectiveness of pneumatic vitreolysis in disrupting vitreomacular traction in our own cohort of patients. METHODOLOGY: Prospective follow-up of 21 eyes of 18 patients with focal VMT (adhesion width < 1500 µm) who underwent intravitreal injection of 0.3 ml of 100% perfluoropropane between January 2015 and December 2020. The patients were observed for 90 days. RESULTS: Release of VMT was achieved on the 28th day of observation in 15 out of 21 eyes (71.4%), and by the 90th day in 19 out of 21 eyes (90.5%). The average width of adhesion in our patients was 382 µm (±212 µm). Average best corrected visual acuity in our cohort was initially 0.77 (±0.21), after 28 days 0.74 (±0.30), and after 3 months 0.82 (±0.21). At the end of the follow-up period, we did not observe a statistically significant improvement in vision. Macular holes developed in two eyes, but spontaneously closed within 1 month of observation, and no more complications were observed in the cohort. CONCLUSION: Pneumatic vitreolysis by intravitreal injection of C3F8 gas is an effective and inexpensive option for the management of symptomatic vitreomacular traction. The incidence of serious adverse events in our follow-up was significantly lower than in recently published series. The method of management should be selected individually according to the parameters of adhesion, macular hole and associated ocular pathologies.

Dynamic angle closure following pars plana vitrectomy with perfluoropropane gas.

Purpose: To report the clinical course of an aphakic patient who developed positional secondary angle closure glaucoma following pars plana vitrectomy (PPV) with perfluoropropane (C3F8) gas tamponade. Observations: A 23-year-old male presented due to a two-year history of vision loss in the left eye. Best-corrected visual acuity (BCVA) was 20/200 and intraocular pressure (IOP) was 12 mm Hg OS. Exam revealed iridodonesis and aphakia of both eyes, and a total RRD in the left eye. The patient underwent scleral buckle plus PPV with 15 % C3F8 gas and was instructed to maintain face-down positioning for 5 days. On post-operative day 1, IOP was 32 mm Hg and exam revealed significant diffuse corneal edema, a large epithelial defect, and 85 % C3F8 fill of the vitreous cavity. Patient was started on IOP-lowering drops but continued to have elevated IOP and corneal epithelial sloughing over the next 3 weeks. He was taken for a superficial keratectomy, but when placed supine under the microscope, a large new gas bubble was visualized overlying the pupil in a now shallow anterior chamber (AC) and IOP was 52 mm Hg. The patient was positioned back upright and the gas bubble migrated posteriorly out of the AC with return of IOP to 25 mm Hg. The dynamic nature of his IOP raised concerns for intermittent angle closure by C3F8 induced by supine positioning. Thus, a pars plana aspiration of the C3F8 gas was performed and resulted in normalization of the IOP. Conclusions and importance: Dynamic, positional secondary angle closure glaucoma can occur after vitrectomy with C3F8 in the setting of aphakia. This is the first report to capture C3F8 gas migration causing intermittent acute angle closure in real-time. Due to its intermittent nature however, the diagnosis may not be initially apparent at the slit lamp. Thus, we suggest this potential complication should be carefully monitored for and discussed when advising post-vitrectomy positioning in aphakic patients.

Outcomes of short- versus long-acting gas tamponades in vitrectomy for rhegmatogenous retinal detachment.

BACKGROUND: In vitrectomy for rhegmatogenous retinal detachment, long-acting gas tamponades (LGT) such as C3F8 or C2F6 may improve surgical success rate due to their prolonged effect compared to a short-acting gas tamponade (SGT) with SF6. On the other hand, SGT allow a significantly faster visual rehabilitation after surgery and may reduce the risk of gas-related complications. As comparative data in retinal detachment surgery is limited, we assessed the outcomes of vitrectomies using either LGT or SGT. METHODS: We retrospectively analyzed 533 eyes of 524 consecutive patients diagnosed with primary rhegmatogenous retinal detachment not complicated by proliferative vitreoretinopathy (PVR) and treated by vitrectomy at two clinical sites. Depending on the site the patients presented at, they received either preferentially LGT (study site 1) or SGT (study site 2). Retinal re-detachment rates during a period of 6 months following surgery were analyzed. RESULTS: At study site 1, 254 of 278 eyes (91.4%) were treated by LGT (C3F8 72.3%; C2F6 19.1%), whereas at study site 2, 246 of 255 eyes (96.5%) received SGT (SF6). Rates of retinal re-detachment in the LGT- and SGT-treated groups were similar with 23 of 254 eyes (9.1%) and 24 of 246 eyes (9.8%), respectively (p = 0.9). Median time to re-detachment was 5.7 weeks in the LGT-treated group and 4.4 weeks in the SGT-treated group (p = 0.4). CONCLUSION: In rhegmatogenous retinal detachment repair by vitrectomy, the use of SGT results in comparable rates of successful retinal re-attachment as LGT. Given the faster visual rehabilitation with SGT, these results suggest SGT as a sensible alternative to LGT in surgery of retinal detachment without PVR.

Therapeutic efficacy of an alpha-particle emitter labeled anti-GD2 humanized antibody against osteosarcoma-a proof of concept study.

PURPOSE: Current treatments for osteosarcoma (OS) have a poor prognosis, particularly for patients with metastasis and recurrence, underscoring an urgent need for new targeted therapies to improve survival. Targeted alpha-particle therapy selectively delivers cytotoxic payloads to tumors with radiolabeled molecules that recognize tumor-associated antigens. We have recently demonstrated the potential of an FDA approved, humanized anti-GD2 antibody, hu3F8, as a targeted delivery vector for radiopharmaceutical imaging of OS. The current study aims to advance this system for alpha-particle therapy of OS. METHODS: The hu3F8 antibody was radiolabeled with actinium-225, and the safety and therapeutic efficacy of the [225Ac]Ac-DOTA-hu3F8 were evaluated in both orthotopic murine xenografts of OS and spontaneously occurring OS in canines. RESULTS: Significant antitumor activity was proven in both cases, leading to improved overall survival. In the murine xenograft's case, tumor growth was delayed by 16-18 days compared to the untreated cohort as demonstrated by bioluminescence imaging. The results were further validated with magnetic resonance imaging at 33 days after treatment, and microcomputed tomography and planar microradiography post-mortem. Histological evaluations revealed radiation-induced renal toxicity, manifested as epithelial cell karyomegaly and suggestive polyploidy in the kidneys, suggesting rapid recovery of renal function after radiation damage. Treatment of the two canine patients delayed the progression of metastatic spread, with an overall survival time of 211 and 437 days and survival beyond documented metastasis of 111 and 84 days, respectively. CONCLUSION: This study highlights the potential of hu3F8-based alpha-particle therapy as a promising treatment strategy for OS.

Efficacy of pneumatic retinopexy in young adults with rhegmatogenous retinal detachment.

Background: In young adults with rhegmatogenous retinal detachment, pneumatic retinopexy can be a cost-effective and minimally invasive highly effective method in suitable cases. Objectives: To evaluate the role of pneumatic retinopexy in the treatment of young adults with rhegmatogenous retinal detachment (RRD) and the factors that may affect the success of pneumatic retinopexy. Design: Retrospective study. Methods: The study included 67 eyes of 67 patients aged between 21 and 40 who underwent pneumatic retinopexy (PR) between January 2015 and June 2021 for primary RRD. We retrospectively analyzed the prognostic factors that may affect the success of PR, such as preoperative age, best corrected visual acuity, tear site, lens condition, and axial length. Results: PR was successful in 61.2% of the patients, whereas 38.8% required secondary surgery. Between the group that had a single surgery (Group 1) and the group that required secondary surgery (Group 2) the tear location, axial length, and volumes of gases used were statistically different (p = 0.04, p < 0.001, and p = 0.02, respectively). There was a significant difference in visual acuity before and after surgery in the group that was successful with a single surgery (Friedman χ2 = 40.051, p < 0.001). There was no significant difference between the two groups in terms of intraocular pressure (p > 0.05), and glaucoma was not observed in the postoperative period. Conclusion: Since it is a minimally invasive and cost-effective method that provides rapid visual rehabilitation, it can be considered as first-line therapy in young adults who are suitable for PR.

Targeting GD2-positive Refractory/Resistant Neuroblastoma and Osteosarcoma with Anti- CD3 x Anti-GD2 Bispecific Antibody Armed T cells.

Background: Since treatment of neuroblastoma (NB) with anti-GD2 monoclonal antibodies provides a survival benefit in children with minimal residual disease and our preclinical study shows that anti-CD3 x anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs) were highly cytotoxic to GD2+ cell lines, we conducted a phase I/II study in recurrent/refractory patients to establish safety and explore the clinical benefit of GD2BATs. Methods: The 3+3 dose escalation study (NCT02173093) phase I involved 9 evaluable patients with NB (n=5), osteosarcoma (OST) (n=3), and desmoplastic small round cell tumors (DSRCT) (n=1) with twice weekly infusions of GD2BATs at 40, 80, or 160 x 106 GD2BATs/kg/infusion with daily interleukin 2 (300,000 IU/m2) and twice weekly granulocyte-macrophage colony stimulating factor (250 µg/m2). Phase II portion of the trial was conducted in patients with NB at the dose 3 level of 160 x 106 GD2BATs/kg/infusion but failed to enroll the planned number of patients. Results: Nine of 12 patients in the phase I completed therapy. There were no dose limiting toxicities (DLTs). All patients developed mild and manageable cytokine release syndrome (CRS) with grade 2-3 fevers/chills, headaches, and occasional hypotension up to 72 hours after GD2BAT infusions. GD2-antibody associated pain was not significant in this study. The median OS for patients in the Phase I and limited Phase II was 18.0 and 31.2 months, respectively, whereas the combined OS was 21.1 months. There was a complete bone marrow response with overall stable disease in one of the phase I patients with NB. Ten of 12 phase II patients were evaluable for response: 1 had partial response. Three additional patients were deemed to have clinical benefit with prolonged stable disease. More than 50% of evaluable patients showed augmented immune responses to GD2+ targets after GD2BATs as measured by interferon-gamma (IFN-γ) EliSpots, Th1 cytokines, and/or chemokines. Conclusions: Our study demonstrated safety of up to 160 x 106 cells/kg/infusion of GD2BATs. Combined with evidence for the development of post treatment endogenous immune responses, this data supports further investigation of GD2 BATs in larger Phase II clinical trials.

A Short-Time Real-World Study of Two Perfluoropropane Tamponade Methods in Pars Plana Vitrectomy for Retinal Detachment.

INTRODUCTION: This real-world study evaluated the efficacy, safety, and operative parameters of two perfluoropropane (C3F8) tamponade methods combined with pars plana vitrectomy (PPV) for retinal detachment (RD). METHODS: A retrospective study of 132 patients (132 eyes) with RD (pure C3F8 in 38 eyes, mixed C3F8 in 94 eyes). All eyes underwent PPV with C3F8 tamponade and were followed up for at least 3 months. Retinal reattachment rate, time of gas configuration and injection, C3F8 dosage, intraocular pressure (IOP), best corrected visual acuity, postoperative ocular inflammation, and patients' complaints were evaluated. RESULTS: The single-surgery retinal reattachment rates of the pure C3F8 group and mixed C3F8 group were 97.4% and 96.8%, respectively, with no significant difference (p = 1.00). The final retinal reattachment rates of the two groups were 100% and 97.2%, respectively, with no significant difference (p = 1.00). The gas configuration time, gas injection time, and C3F8 dosage were significantly less in the pure C3F8 group (all p < 0.001). Time, but not group, was the influencing factor of postoperative IOP changes in the two groups (p < 0.001, p = 0.547, respectively). Compared with the baseline, the IOP estimates of the pure C3F8 group showed a significant increase immediately after surgery (p < 0.001), and the mixed C3F8 group showed a significant increase immediately and 1-2 days after surgery (all p < 0.05). There was no statistical difference in ocular inflammation (p = 0.339) and patients' complaints of discomfort (p = 0.175) between the two groups. CONCLUSION: Both the two methods of C3F8 tamponade combined with PPV in RD patients showed good efficacy and safety, but the clinical operation of pure C3F8 tamponade was more convenient and eco-friendly.

Immunotherapy with anti-GD2 monoclonal antibody in infants with high-risk neuroblastoma.

Anti-GD2 monoclonal antibodies (mAb) improve the prognosis of high-risk neuroblastoma (HR-NB). Worldwide experience almost exclusively involves toddlers and older patients treated after multimodality or second-line therapies, that is, many months postdiagnosis. In contrast, at our center, infants received anti-GD2 mAbs because this immunotherapy started during or immediately after induction chemotherapy. We now report on the feasibility, safety, and long-term survival in this vulnerable age group. Thirty-three HR-NB patients were <19 months old when started on 3F8 (murine mAb; n = 21) or naxitamab (humanized-3F8; n = 12), with 30″ to 90″ intravenous infusions. Patients received analgesics and antihistamines. Common toxicities (pain, urticaria, cough) were manageable, allowing outpatient treatment. Capillary leak, posterior reversible encephalopathy syndrome, and mAb-related long-term toxicities did not occur. Two 3F8 cycles were aborted due to bradycardia (a preexisting condition) and asthmatic symptoms, respectively. One patient received ½ dose of Day 1 naxitamab because of hypotension; full doses were subsequently administered. Post-mAb treatments included chemotherapy, radiotherapy, and anti-NB vaccine. Among 3F8 patients, 17/21 are in complete remission off all treatment at 5.6+ to 24.1+ (median 13.4+) years from diagnosis. Among naxitamab patients, 10/12 remain relapse-free post-mAb at 1.7+ to 4.3+ (median 3.1+) years from diagnosis. Toxicity was similar with short outpatient infusions and matched that observed with these and other anti-GD2 mAbs in older patients. These findings were reassuring given that naxitamab is dosed >2.5× higher (~270 mg/m2 /cycle) than 3F8, dinutuximab, and dinutuximab beta (70-100 mg/m2 /cycle). HR-NB in infants proved to be highly curable.

Effect Of Intravitreal Perfluoro Propane (C3f8) In The Management Of Symptomatic Vitreomacular Traction.

BACKGROUND: To study the efficacy of a single 0.3ml of C3F8 injection for the treatment of symptomatic VMT. METHODS: In this retrospective interventional study a total of nine patients were recruited. The mean age was 67 years. Patients had a follow-up at one week and four weeks post injections. VMT status was confirmed on repeat Oct scan. RESULTS: There was a complete release of VMT In 4 patients after one week and further release of VMT was observed in two more patients after four weeks. Hence six out of nine patients had complete resolution of pathology following C3F8 injection. CONCLUSIONS: Intravitreal C3F8 is a cheaper and safer option for the treatment of vitreomacular traction as compared to pars plana vitrectomy or Ocriplasmin.

Anti-GD2 antibody for radiopharmaceutical imaging of osteosarcoma.

PURPOSE: Osteosarcoma (OS) is the most frequently diagnosed bone cancer in children with little improvement in overall survival in the past decades. The high surface expression of disialoganglioside GD2 on OS tumors and restricted expression in normal tissues makes it an ideal target for anti-OS radiopharmaceuticals. Since human and canine OS share many biological and molecular features, spontaneously occurring OS in canines has been an ideal model for testing new imaging and treatment modalities for human translation. In this study, we evaluated a humanized anti-GD2 antibody, hu3F8, as a potential delivery vector for targeted radiopharmaceutical imaging of human and canine OS. METHODS: The cross-reactivity of hu3F8 with human and canine OS cells and tumors was examined by immunohistochemistry and flow cytometry. The hu3F8 was radiolabeled with indium-111, and the biodistribution of [111In]In-hu3F8 was assessed in tumor xenograft-bearing mice. The targeting ability of [111In]In-hu3F8 to metastatic OS was tested in spontaneous OS canines. RESULTS: The hu3F8 cross reacts with human and canine OS cells and canine OS tumors with high binding affinity. Biodistribution studies revealed selective uptake of [111In]In-hu3F8 in tumor tissue. SPECT/CT imaging of spontaneous OS canines demonstrated avid uptake of [111In]In-hu3F8 in all metastatic lesions. Immunohistochemistry confirmed the extensive binding of radiolabeled hu3F8 within both osseous and soft lesions. CONCLUSION: This study demonstrates the feasibility of targeting GD2 on OS cells and spontaneous OS canine tumors using hu3F8-based radiopharmaceutical imaging. Its ability to deliver an imaging payload in a targeted manner supports the utility of hu3F8 for precision imaging of OS and potential future use in radiopharmaceutical therapy.

Surgical Management of Corneal Hydrops: Case Series

Descemet's membrane (DM) rupture/detachments have traditionally been treated conservatively, with limited efficacy and a long rehabilitation period that significantly affects patients' vision and quality of life. Although there are no established gold standards for the timing and nature of treatment, with this series of 4 cases we aimed to highlight the importance of the current optimal intervention methods. The first two patients were treated with anterior chamber injection of isoexpansile 14% C3F8 due to acute hydrops associated with keratoglobus in the first case and keratoconus in the second case. The third patient had keratoglobus and chronic hydrops complicated by multiple stromal clefts detected on anterior segment optical coherence tomography, and the fourth patient had a chronic broad DM detachment which occurred after cataract surgery. Both of these patients were treated with intracameral C3F8 injection together with corneal compressive sutures. In all four cases, DM reattached completely and effectively with surgical intervention. Surgical management of DM rupture/detachment with intracameral gas injection and compressive corneal sutures seems to provide fast symptomatic relief and less healing-related corneal scarring with better visual rehabilitation, and may alleviate the need for corneal transplant surgery in this group of patients.

The outcomes of intravitreal C3F8 gas tamponade combined with laser photocoagulation treatment for optic disc pit maculopathy.

PURPOSE: To share the anatomical results and visual outcomes of intravitreal gas tamponade combined with laser photocoagulation treatment for optic disc pit maculopathy (ODPM). METHODS: Intravitreal gas tamponade combined with laser photocoagulation treatment was performed on six consecutive patients with ODPM. A 0.3 mL of 100% perfluoropropane (C3F8) gas was injected intravitreally. The patients were then asked to maintain prone position until the C3F8 gas disappeared. Laser photocoagulation was performed the day after the procedure. The outcomes were determined by spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA). RESULTS: In the present study, visual improvement and reduction in serous macular detachment were observed in 83% of the ODPM patients. Complete retinal reattachment was achieved in 66% of the ODPM patients. In one patient, no regression was observed after the repeated treatment, and pars plana vitrectomy was performed. The final BCVA improved in five eyes and unchanged in one eye. No postoperative complications were observed during the follow-up period in any patient. CONCLUSIONS: Intravitreal C3F8 gas tamponade combined with laser photocoagulation procedure is an effective, minimally invasive, and cost-effective treatment method for ODPM.

Pneumatic retinopexy: an update.

Pneumatic retinopexy (PR) is a minimally invasive, non-incisional procedure for repairing uncomplicated rhegmatogenous retinal detachment. It consists of an intravitreal gas injection followed by the maintenance of a postoperative head position and the use of laser or cryopexy to seal the retinal breaks. It was initially indicated for a single or a group of retinal breaks no larger than 1 clock hour involving the superior 8 clock hours in phakic eyes with no proliferative vitreoretinopathy. We aim to perform a narrative review on pneumatic retinopexy since the last major review of 2008, based on a Medline search up to June 20 2021 using multiple search words including pneumatic retinopexy, pneumoretinopexy, retinal detachment, and pars plana vitrectomy. Indications for PR have been expanded and include pseudophakic eyes, eyes with mild PVR, and even breaks in the inferior fundus. Depending on the case selection, PR has a single-operation success rate ranging from 45 to 80%. Despite the lower single operation success rate, the functional outcomes of those eyes repaired successfully by primary PR exceed those of scleral buckling (SB) and pars plana vitrectomy (PPV). Best corrected visual acuity, metamorphopsia scores, mental health scores, and vision-related functioning scores were all better in PR-treated eyes compared to PPV-treated eyes. PR should be strongly considered for eligible patients with a primary uncomplicated rhegmatogenous retinal detachments.

Suprachoroidal Gas: A Rare Complication of Intravitreal Injection of Perfluoropropane.

This is a case report of a 75-year-old pseudophakic male, who presented with a massive submacular hemorrhage on a background of neovascular age-related macular degeneration. Intravitreal perfluoropropane was used to attempt pneumatic displacement of the submacular hemorrhage. The next day, subconjunctival gas was observed, with no gas seen in the vitreous cavity. Fundal examination showed suprachoroidal detachment. CT images confirmed gas entrapment, with no choroidal hemorrhage identified. The following case report describes suprachoroidal gas as a complication of intravitreal injection of perfluoropropane for pneumatic displacement of submacular hemorrhage. To our knowledge, this is the first such case in the literature. We describe the approach in differentiating suprachoroidal gas from hemorrhage and comment on a plausible mechanism for this complication. This report also serves as a review of the current state of knowledge in the area of suprachoroidal gas as a complication of pneumatic retinopexy and sutureless vitrectomy.

Naxitamab: a humanized anti-glycolipid disialoganglioside (anti-GD2) monoclonal antibody for treatment of neuroblastoma.

Therapy for high-risk neuroblastoma (HR NBL) is comprised of multimodal therapy including chemotherapy, surgery, radiation therapy, myeloablative therapy followed by autologous hematopoietic stem cell transplant, and immunotherapy. GD2 is a disialoganglioside that is highly expressed on the surface of neuroblastoma cells, with limited expression on normal tissues, which makes it an attractive target for immunologic therapy. The combination of immunotherapy with murine and chimeric anti-GD2 antibody formulations has improved outcomes compared with standard therapy in HR NBL patients. Naxitamab (Danyelza), a fully humanized anti-GD2 antibody, was developed at Memorial Sloan Kettering Cancer Center (MSKCC) to mitigate adverse reactions related to intolerance of foreign murine and chimeric antigens. Phase I and II studies demonstrating the tolerability and efficacy of naxitamab in patients with relapsed/refractory (r/r) HR NBL prompted its approval by the U.S. Food and Drug Administration (FDA) in 2020 for HR NBL with bone or bone marrow involvement. Initial outcomes with naxitamab are encouraging; however, future trials to maximize drug tolerance and elucidate its optimal role in neuroblastoma therapy in conjunction with other treatment strategies are needed. This review discusses the use of naxitamab in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of r/r HR NBL.

Pneumatic Vitreolysis with Perfluoropropane for Vitreomacular Traction with and without Macular Hole: DRCR Retina Network Protocols AG and AH.

PURPOSE: To evaluate pneumatic vitreolysis (PVL) in eyes with vitreomacular traction (VMT) with and without full-thickness macular hole (FTMH). DESIGN: Two multicenter (28 sites) studies: a randomized clinical trial comparing PVL with observation (sham injection) for VMT without FTMH (Protocol AG) and a single-arm study assessing PVL for FTMH (Protocol AH). PARTICIPANTS: Participants were adults with central VMT (vitreomacular adhesion was ≤3000 µm). In Protocol AG, visual acuity (VA) was 20/32 to 20/400. In Protocol AH, eyes had a FTMH (≤250 µm at the narrowest point) and VA of 20/25 to 20/400. METHODS: Pneumatic vitreolysis using perfluoropropane (C3F8) gas. MAIN OUTCOME MEASURES: Central VMT release at 24 weeks (Protocol AG) and FTMH closure at 8 weeks (Protocol AH). RESULTS: From October 2018 through February 2020, 46 participants were enrolled in Protocol AG, and 35 were enrolled in Protocol AH. Higher than expected rates of retinal detachment and tear resulted in early termination of both protocols. Combining studies, 7 of 59 eyes (12% [95% CI, 6%-23%]; 2 eyes in Protocol AG, 5 eyes in Protocol AH) that received PVL developed rhegmatogenous retinal detachment (n = 6) or retinal tear (n = 1). At 24 weeks in Protocol AG, 18 of 23 eyes in the PVL group (78%) versus 2 of 22 eyes in the sham group (9%) achieved central VMT release without rescue vitrectomy (adjusted risk difference, 66% [95% CI, 44%-88%]; P< 0.001). The mean change in VA from baseline at 24 weeks was 6.7 letters in the PVL group and 6.1 letters in the sham group (adjusted difference, -0.8 [95% CI, -6.1 to 4.5]; P = 0.77). In Protocol AH, 10 of 35 eyes (29% [95% CI, 16%-45%]) achieved FTMH closure without rescue vitrectomy at 8 weeks. The mean change in VA from baseline at 8 weeks was -1.5 letters (95% CI, -10.3 to 7.3 letters). CONCLUSIONS: In most eyes with VMT, PVL induced hyaloid release. In eyes with FTMH, PVL resulted in hole closure in approximately one third of eyes. These studies were terminated early because of safety concerns related to retinal detachments and retinal tears.

A novel multimeric IL15/IL15Rα-Fc complex to enhance cancer immunotherapy.

The role of T cells in controlling human cancers is well known. Their success requires continued persistence in vivo and efficient trafficking to tumor sites, requirements shared by other effectors such as Natural Killer (NK) cells. To date, cytokine IL2 remains the only clinically approved cytokine therapy available to expand, maintain, and activate these effector lymphoid cells, but toxicities can be severe. Cytokine IL15 offers similar T cell proliferation and activation properties, but without the unwanted side-effects seen with IL2. Several IL15-cytokine fusion proteins have been developed to improve their in vivo function, typically exploiting the IL15Rα to complex with IL15, to extend serum half-life and increase affinity for IL15ß receptor on immune cells. Here we describe a novel IL15 complex incorporating the full-length IL15Rα to complex with wild type IL15 to form spontaneous trimers of dimers (6 IL15 + 6 IL15Rα) during co-expression, resulting in a substantial increase in serum half-life and enhancement of in vivo cytokine effect on IgG or T cell engaging antibody-dependent cell-mediated cytotoxicities, when compared to alternative strategies.

Evaluating the safety and efficacy of compression sutures with intracameral perfluoropropane (C3F8) in the management of acute corneal hydrops.

BACKGROUND: To evaluate the safety and efficacy of using corneal compression sutures with intracameral perfluoropropane (C3F8) in patients presenting with acute corneal hydrops in ectatic disorders. METHODS: A retrospective analysis was done for 43 eyes of patients of acute corneal hydrops, managed using a combination of intracameral 14% C3F8 and full-thickness compression sutures. Time for resolution of edema, corneal thickness (CT) change on anterior segment ocular coherence tomography (ASOCT), and visual outcomes were assessed. RESULTS: Corneal edema resolved with a mean duration of 14.8 ± 3.5 days (range 10-21). The mean CT on ASOCT decreased from a mean of 1437 µm (689-2770 µm) preoperatively to 543 µm (434 -66 µm) on the complete resolution of corneal edema. CONCLUSION: Our results suggest that full-thickness compression sutures and intracameral C3F8 injection can restore the imperviousness of posterior stroma. This technique appears to be a safe and effective technique for faster resolution of corneal edema post hydrops.

Air vs Gas Tamponade During Macular Hole Repair Surgery.

Purpose: This work investigates the visual and anatomical outcomes of full-thickness macular hole (FTMH) repair surgery using air in comparison to gas tamponade. Methods: A retrospective consecutive review of medical records was undertaken of all patients undergoing pars plana vitrectomy for idiopathic FTMH at an academic practice from January 2010 to May 2017. Each operative report was reviewed to investigate the agent used for tamponade at the end of the surgery. Preoperative hole duration and size as measured using optical coherence tomography as well as successful postoperative hole closure were recorded. Use of gas or air was not randomized and was instilled at surgeon discretion. Results: The final analysis included 211 eyes. Gas was used as the tamponade agent in 171 of the 211 eyes; most of these eyes (144 of 171) received sulfur hexafluoride (SF6) and the remainder received perfluoropropane (C3F8). Forty eyes underwent only a complete fluid-air exchange without any gas placement following vitrectomy. There was no statistically significant difference between the 2 groups in mean preoperative macular hole size (P = .43). Nine of the 171 macular holes receiving gas tamponade failed to close (5.3%). One of the 40 macular holes receiving only air failed to close (2.5%). There was no statistically significant difference in hole closure rates between the 2 groups (P = .45). Conclusions: Air served as an equally efficacious internal tamponade agent in comparison to nonexpansile gas following idiopathic FTMH repair surgery.

Clinical profile and management outcomes of traumatic submacular hemorrhage.

PURPOSE: To evaluate the anatomical and functional outcome of patients with traumatic submacular hemorrhage (SMH). METHODS: A retrospective, interventional case series of patients presenting between January 2016 and April 2018 was carried out at 4 tertiary eye care centers of India. Medical records of the patients with a history of blunt trauma and SMH were retrospectively reviewed. The intervention done was any one of the following: pneumatic displacement with 0.3 ml of intravitreal gas [100% perfluoropropane (C3F8) gas], pneumatic displacement with intravitreal 0.3 ml of 100% C3F8 gas combined with 100 µg/0.1 ml of recombinant tissue plasminogen activator (r-tpa), pars plana vitrectomy (PPV) with subretinal r-tpa and gas tamponade. The primary outcome measures included change in visual and anatomical status. RESULTS: Twenty eyes of 20 patients with blunt trauma were analyzed. Thirteen patients had small size SMH, 5 patients had medium size SMH, and 2 patients had massive size SMH. Sixteen patients had a favorable functional outcome, and eighteen patients had favorable anatomical outcome. The size and duration of post-traumatic SMH did not significantly affect the anatomical (P = 0.123) or functional (P = 0.293) outcome in our study. The patients who presented with initial visual acuity of 6/60 or better showed better functional outcome, which was statistically significant (P = 0.007). CONCLUSION: Minimally non-invasive procedure including intravitreal r-tpa and gas appear to be effective in the displacement of post-traumatic SMH.