Focal electrical stimulation of human retinal ganglion cells for vision restoration.

Objective. Vision restoration with retinal implants is limited by indiscriminate simultaneous activation of many cells and cell types, which is incompatible with reproducing the neural code of the retina. Recent work has shown that primate retinal ganglion cells (RGCs), which transmit visual information to the brain, can be directly electrically activated with single-cell, single-spike, cell-type precision - however, this possibility has never been tested in the human retina. In this study we aim to characterize, for the first time, direct in situ extracellular electrical stimulation of individual human RGCs.Approach. Extracellular electrical stimulation of individual human RGCs was conducted in three human retinas ex vivo using a custom large-scale, multi-electrode array capable of simultaneous recording and stimulation. Measured activation properties were compared directly to extensive results from macaque.Main results. Precise activation was in many cases possible without activating overlying axon bundles, at low stimulation current levels similar to those used in macaque. The major RGC types could be identified and targeted based on their distinctive electrical signatures. The measured electrical activation properties of RGCs, combined with a dynamic stimulation algorithm, was sufficient to produce an evoked visual signal that was nearly optimal given the constraints of the interface.Significance. These results suggest the possibility of high-fidelity vision restoration in humans using bi-directional epiretinal implants.

Displacement of Submacular Hemorrhage With Subretinal Injection of Recombinant Tissue Plasminogen Activator and Gas Tamponade in the Setting of Myopic Degeneration.

Myopic submacular hemorrhage (SMH) usually arises from either a break in Bruch's membrane (lacquer cracks) that damages the underlying choriocapillaris or the development of a choroidal neovascular membrane (CNVM) at the sites of prior lacquer cracks.1,2 In pathologic myopia (PM), axial elongation leads to thinning of the choroid and retinal pigment epithelium, predisposing to rupture of Bruch's membrane.3 If large hemorrhages involving the fovea are left untreated, subretinal hemorrhage and CNVM can cause devastating long-term vision loss due to irreversible retinal atrophy.4 In this video, the authors describe their technique of using a subretinal injection of recombinant tissue plasminogen activator with a concurrent gas tamponade to displace SMH.

Optical Coherence Tomography Angiography Findings in Chronic Central Serous Chorioretinopathy After Photodynamic Therapy.

BACKGROUND AND OBJECTIVES: To report the acute and long-term choroidal findings in patients with chronic central serous chorioretinopathy (CCSC) undergoing half-fluence photodynamic therapy (PDT). PATIENTS AND METHODS: This is a prospective, consecutive, interventional, noncomparative case series at a tertiary referral vitreoretinal practice. Twenty-one eyes from 21 patients are included. RESULTS: Among 21 eyes, all had improved vision following PDT during a mean of 5.2 months ± 4.8 months of follow-up. The incidence of choroidal neovascular membranes was 19.0% (four in 21), with only one of these eyes (4.8%) requiring intravitreal anti-vascular endothelial growth factor injections. Changes in the choriocapillaris were noted in 28.6% (six of 21) eyes following PDT. Eighteen patients (85.7%) demonstrated striking regions of dilated choroidal vessels closely corresponding to regions of outer retinal changes and subretinal fluid. Twenty patients (95.2%) experienced resolution of subretinal fluid within 3 months of receiving PDT. CONCLUSION: Optical coherence tomography angiography may provide new insight into the pathogenesis of CCSC, namely in identifying a correlation between structures of the deep choroid and changes in the retinal pigment epithelium and neurosensory retina. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:25-32.].

Orbital and chorioretinal manifestations of Erdheim-Chester disease treated with vemurafenib.

PURPOSE: We report a patient with severe multi-organ dysfunction of unknown origin who presented with bilateral orbital and chorioretinal manifestations that led to the diagnosis of Erdheim-Chester Disease (ECD). OBSERVATIONS: ECD is a rare, histiocytic, proliferative disorder characterized by multi-systemic organ involvement that has historically lacked effective therapy. Our patient underwent genetic testing that was positive for the BRAF V600E mutation; therefore, the patient was treated with vemurafenib. CONCLUSIONS AND IMPORTANCE: This case demonstrates the rare orbital and intraocular manifestations of ECD and the unfortunate impact of a delayed diagnosis, the importance of early gene therapy testing for management decisions, and the utilization of targeted directed therapy to improve visual outcomes and quality of life.

The superficial and deep retinal capillary plexus in cases of fovea plana imaged by spectral-domain optical coherence tomography angiography.

PURPOSE: To describe the appearance of the superficial and deep retinal capillary plexi in three patients with fovea plana of differing severity using spectral-domain optical coherence tomography angiography (OCTA). OBSERVATIONS: In the first case of grade 1 fovea plana (a patient with 20/25 vision), OCTA showed an orderly branching pattern of vessels from the superficial and deep retinal plexi extending to the center of the fovea. The second case of grade 3 fovea plana (20/30 vision) showed some disruption of the orderly vascular pattern with small caliber vessels from both superficial and deep layers densely covering the fovea center. Case 3 represented a patient with grade 4 fovea plana associated with PAX6 mutation and poor visual acuity. OCTA revealed a disorganized pattern of large and small caliber vessels from the superficial capillary network extending into the center of the fovea. CONCLUSIONS AND IMPORTANCE: Previously available imaging modalities were unable to specifically target different layers of the retinal vasculature. Using OCTA we have been able to show progressive changes in the vascular pattern in the deep and superficial retinal layers of patients with different grades of fovea plana. This novel imaging technique may play a role in the classification and assessment of patients with fovea plana.

AFLIBERCEPT FOR THE TREATMENT OF RETINAL PIGMENT EPITHELIAL DETACHMENTS.

PURPOSE: To compare anatomical and visual acuity outcomes of eyes with persistent pigment epithelial detachments (PEDs) secondary to exudative age-related macular degeneration despite ranibizumab or bevacizumab treatment. METHODS: After institutional review board approval, 40 eyes with PEDs switched from ranibizumab or bevacizumab to intravitreal aflibercept were compared for logMAR visual acuity, central subfield thickness on spectral domain optical coherence tomography, and PED height. Using paired t-tests, these parameters at baseline, after 3 consecutive injections, and 1 year after the switch were compared. RESULTS: Baseline visions of 20/61 ± 3.99 lines declined after 3 injections with aflibercept by 0.39 ± 2.43 lines (P = 0.32) and continued to fall after 1 year by 1.27 ± 3.48 lines (P = 0.03). Central subfield thickness was reduced after 3 injections (9.1 ± 52.0 µm, P = 0.27) and after 1 year (24.4 ± 55.3 µm, P = 0.01). The height of PEDs decreased by 31.7 ± 71.53 µm (P = 0.008) after 3 injections and by 47.81 ± 77.94 µm (P < 0.001) after 1 year. CONCLUSION: Switching to aflibercept from ranibizumab or bevacizumab resulted in a reduction in the height of PED and central subfield thickness, but a trend toward worse visual acuity 1 year after the switch.

Experience With Aflibercept for the Treatment of Neovascular Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: Describe visual and anatomic outcomes of eyes with exudative age- related macular degeneration (AMD) after treatment with aflibercept. PATIENTS AND METHODS: Eyes treated with intravitreal injections of aflibercept for exudative AMD were retrospectively reviewed to compare visual acuity and central subfield thickness (CST) on optical coherence tomography. RESULTS: A total of 142 eyes receiving aflibercept were previously treated with bevacizumab or ranibizumab intravitreal injections. Baseline vision was 20/73 ± 5.18 lines when switched to aflibercept. It improved by 0.2 ± 1.91 lines (P =.14) after three injections but decreased by 0.45 ± 2.9 lines (P = .06) after 1 year of follow-up. The reduction in CST was 9.9 ± 46.5 µm (P = .06) after three injections and grew to 19.3 ± 50.6 µm (P = .002), a statistically significant amount, after 1 year. CONCLUSION: Switching to aflibercept resulted in no clinically significant differences in visual acuity after 1 year. There was a significant reduction in CST, but this may not be clinically significant.

NOCARDIA CHOROIDAL ABSCESS: Risk Factors, Treatment Strategies, and Visual Outcomes.

PURPOSE: To describe the risk factors, clinical course, ancillary test findings, treatment strategies, and visual outcomes of a series of patients with choroidal abscesses caused by endogenous Nocardia. METHODS: This retrospective, consecutive noncomparative case series included all patients with Nocardia ocular infections at 3 tertiary medical centers over the past 20 years. RESULTS: Five eyes in 5 patients were identified with choroidal abscesses because of Nocardia. All patients were immunocompromised: one suffered from AIDS and four had autoimmune disorders. Three of the 5 patients (60%) underwent systemic evaluation, and in all 3, nonocular nocardiosis was identified. Four patients (80%) underwent diagnostic ophthalmic surgery and received systemic and intravitreal antibiotics. The final patient deferred these interventions. Outcomes at the last follow-up examination were 20/25, 1/200, hand motion at 1 foot, and 2 patients underwent enucleation. Mean follow-up (± standard deviation) was 159 (± 103) days. CONCLUSION: Immunosuppression is the most significant risk factor for developing Nocardia choroidal abscesses. Definitive diagnosis generally requires subretinal biopsy, which is also critical to implementing appropriate antibiotic therapy.

Hemorrhage as a sign of treatment failure after intra-arterial chemotherapy in retinoblastoma.

Intra-arterial melphalan chemotherapy (IAC) continues to demonstrate excellent utility in the treatment of retinoblastoma. We present the case of a 3-month-old boy diagnosed with with unilateral, advanced stage 5B retinoblastoma and a Coats' response in the right eye. After laser therapy he received 3 doses of IAC. Intraretinal hemorrhaging, first noted after the second dose and worsening after the third, preceded complex exudative retinal detachment. With little visual potential and evidence of atropy, the eye was enucleated. This case illustrates that intraretinal hemorrhage may serve as an early predictor of treatment failure.

Risk factors for respiratory depression in patients undergoing retrobulbar block for vitreoretinal surgery.

BACKGROUND AND OBJECTIVE: To determine the risk factors for respiratory depression during retrobulbar block administration before vitreoretinal surgery. PATIENTS AND METHODS: Prospective, observational case series of 113 patients undergoing monitored anesthesia care and retrobulbar block before vitreoretinal surgery at a tertiary medical center. RESULTS: Chin lift, jaw thrust, and bag mask ventilation were performed in eight (7.1%), nine (8%), and six (5.3%) patients, respectively. No patients required intubation. Age, sex, body mass index, history of obstructive sleep apnea, American Society of Anesthesiologists physical status level, and baseline oxygen saturation were not predictive of airway intervention. Of the four anesthetic agents utilized (midazolam, fentanyl, alfentanil, and propofol), only propofol and fentanyl were associated with an increased risk for clinically significant apnea. Use of three medications for sedation was associated with a 5.4-fold increase in the relative risk of requiring a respiratory rescue intervention. CONCLUSION: During preoperative sedation for retrobulbar block administration, the use of propofol, fentanyl, or a combination of three anesthetics is associated with a statistically significant increase in the risk for respiratory depression requiring resuscitation.

Exogenous fungal endophthalmitis: an analysis of isolates and susceptibilities to antifungal agents over a 20-year period (1990-2010).

PURPOSE: To describe the isolates and susceptibilities to antifungal agents for patients with culture-proven exogenous fungal endophthalmitis. DESIGN: Noncomparative case series. METHODS: The clinical records of all patients treated for culture-proven exogenous fungal endophthalmitis at a university referral center from 1990 to 2010 were reviewed. Specimens initially used for diagnosis were recovered from the microbiology department and then underwent antifungal sensitivity analysis. RESULTS: The antifungal susceptibilities of 47 fungal isolates from culture-positive fungal endophthalmitis are reported. Included are 14 isolates from yeast and 33 from mold. The mean (±standard deviation) minimum inhibitory concetrations (MICs) for amphotericin B (2.6 ± 3.5 µg/mL), fluconazole (36.9 ± 30.7 µg/mL), and voriconazole (1.9 ± 2.9 µg/mL) are reported. Presumed susceptibility to oral fluconazole, intravenous amphotericin B, intravitreal amphotericin B, oral voriconazole, and intravitreal voriconazole occurred in 34.8%-43.5%, 0-8.3%, 68.8%, 69.8%, and 100% of isolates, respectively. CONCLUSIONS: Based on this laboratory study of isolates from exogenous fungal endophthalmitis, intravitreal voriconazole appears to provide the broadest spectrum of antifungal coverage and, as such, may be considered for empiric therapy of endophthalmitis caused by yeast or mold.

Retinal breaks due to intravitreal ocriplasmin.

Ocriplasmin represents a new treatment option for numerous vitreoretinopathies involving an abnormal vitreomacular interface. While the drug may circumvent the traditional risks of surgical treatment, pharmacologic vitreolysis is not devoid of risk itself. This report presents two cases, one of vitreomacular traction syndrome and the other of a full-thickness macular hole, both of which were treated with an intravitreal injection of ocriplasmin. Notably, in both cases, vitreomacular traction of the macula appears to have been alleviated; however, failure to completely relieve vitreoretinal traction from the peripheral retina generated retinal breaks with one patient eventually developing a macula-involving retinal detachment. Thus, even in instances of 'successful' pharmacologic treatment of vitreomacular traction, continued follow-up evaluation is essential.

Exudative retinal detachment following photocoagulation in older premature infants for retinopathy of prematurity: description and management.

PURPOSE: To describe exudative retinal detachment following laser photocoagulation after 40 weeks of postmenstrual age (PMA) for retinopathy of prematurity in premature infants, its medical management, and outcomes. METHODS: Two pediatric vitreoretinal surgeons at 2 different quaternary care institutions retrospectively identified children who received laser photocoagulation after 40 weeks of PMA and subsequently developed exudative detachment. Hospital course, management, and outcomes were identified. RESULTS: Three infants were identified that developed exudative retinal detachments following laser photocoagulation for retinopathy of prematurity after 40 weeks of PMA. The average gestational age was 25 weeks with an average birth weight of 650 g. All babies were Zone II at initial examination and developed Stage 3 with pre-plus or plus disease after 40 weeks of PMA (average 42 weeks of PMA). Therapy consisted of topical cyclogyl (0.5%) and topical prednisolone acetate (1%) to the affected eyes and intravenous dexamethasone in all cases. The exudative retinal detachments resolved by 50 weeks of PMA in all infants. Hard exudates following resolution were found in all eyes. Two eyes demonstrated temporal macular dragging. CONCLUSION: Premature infants who require laser photocoagulation for retinopathy of prematurity at >40 weeks of PMA may be predisposed to develop exudative retinal detachments. In the absence of identifiable traction, systemic corticosteroid use can be considered to achieve favorable anatomic outcomes.

Severe worsening of diabetic retinopathy following bariatric surgery.

Intensive glycemic control results in long-term reduction of diabetic retinopathy, although initial short-term worsening of retinopathy is not uncommon. The authors report a patient with a history of stable diabetic retinopathy who, despite achieving abrupt glycemic control following laparoscopic Roux-en-Y gastric bypass surgery, suffered rapid worsening of her retinopathy within 1 month of surgery. Hemoglobin A1c levels were 8.8 preoperatively and declined to 7.2 at 3.5 months postoperatively. Although visual function in the left eye was spared, useful visual acuity was lost in the right eye. Retinal evaluation is recommended in all patients with diabetes mellitus who are considering bariatric surgery, with close follow-up as warranted.