Eleftherios I. Paschalis's research while affiliated with Harvard Medical School and other places

Publications (95)

Article
Full-text available
In this study, a one-step electrochemical aptasensor was developed to detect the biomarker vascular endothelial growth factor (VEGF), an important protein in the pathogenesis of many retinal diseases, including age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, and retinal vein occlusion. The aptamer has a good affi...
Article
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Retinitis pigmentosa (RP) is an intractable inherited disease that primarily affects the rods through gene mutations followed by secondary cone degeneration. This cone-related dysfunction can lead to impairment of daily life activities, and ultimately blindness in patients with RP. Paradoxically, microglial neuroinflammation contributes to both pro...
Preprint
Full-text available
Colony-stimulating factor 1 receptor (CSF1R) inhibition has been proposed as a specific method for microglia depletion. However, recent work revealed that in addition to microglia, CSF1R inhibition also affects other innate immune cells, such as peripheral monocytes and tissueresident macrophages of the lung, liver, spleen, and peritoneum. Here, we...
Article
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When ionizing irradiation interacts with a media, it can form reactive species that can react with the constituents of the system, leading to eradication of bioburden and sterilization of the tissue. Understanding the media's properties such as polarity is important to control and direct those reactive species to perform desired reactions. Using et...
Article
Purpose To assess the prevalence of autoimmune diseases (AiD) in patients with primary open angle glaucoma (POAG) undergoing ophthalmic surgery. Design Retrospective cross-sectional study. Participants POAG patients undergoing any ophthalmic surgery and control subjects undergoing cataract surgery at the Massachusetts Eye and Ear from March 2019...
Preprint
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Limbal stem cell (LSC) deficiency is a frequent and severe complication after chemical injury to the eye. Previous studies have assumed that this is mediated by direct chemical injury. Here we show that LSC loss can occur even without direct chemical injury to LSCs. Elevation of anterior chamber (AC) pH causes acute uveal stress, release of inflamm...
Article
Inadequate supplies of donor corneas have evoked an escalating interest in corneal xenotransplantation. However, innate immune responses contribute significantly to the mechanism of xenograft rejection. We hypothesized that complement component C5 and TLR co-receptor CD14 inhibition would inhibit porcine cornea induced innate immune responses. Ther...
Article
Purpose To evaluate the effects of electron-beam (E-beam) irradiation on the human cornea and the potential for E-beam sterilization of Boston keratoprosthesis (BK) devices when pre-assembled with a donor cornea prior to sterilization. Methods Human donor corneas and corneas pre-assembled in BK devices were immersed in recombinant human serum albu...
Article
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Electron beam (E‐beam) irradiation is an attractive and efficient method for sterilizing clinically implantable medical devices made of natural and/or synthetic materials such as poly(methyl methacrylate) (PMMA). As ionizing irradiation can affect the physicochemical properties of PMMA, understanding the consequences of E‐beam sterilization on the...
Article
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Purpose: To evaluate titanium (Ti) sputtering of the poly(methyl methacrylate) (PMMA) stem of the Boston Keratoprosthesis (BK) as a method to enhance interfacial adhesion between the PMMA and the recipient corneal tissue. Methods: PMMA specimens were plasma treated with Ar/O2 and coated with Ti using a DC magnetron sputtering instrument. The top...
Article
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Purpose: To benchmark the optical performance of Boston Keratoprosthesis (B-KPro). Methods: Back focal lengths (BFL) of B-KPros for various eye axial lengths were measured using an optical bench, International Organization for Standardization-certified for intraocular lens characterization, and compared against manufacturer's specification. The...
Article
Full-text available
Colony-stimulating factor 1 receptor (CSF1R) inhibition has been proposed as a method for microglia depletion, with the assumption that it does not affect peripheral immune cells. Here, we show that CSF1R inhibition by PLX5622 indeed affects the myeloid and lymphoid compartments, causes long-term changes in bone marrow-derived macrophages by suppre...
Article
Purpose: To evaluate the antifungal properties of topical antibiotics (already being used successfully to prevent bacterial endophthalmitis) and some promising antiseptics for antifungal prophylaxis in the setting of artificial corneal implantation. Methods: Several commonly used antibiotics for antimicrobial prophylaxis after artificial corneal...
Article
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Purpose: To describe a novel microporous drug delivery system (DDS) for sustained anti- vascular endothelial growth factor (VEGF) delivery to the eye and to evaluate its efficacy in a corneal injury model. Methods: A macro-porous DDS (1.5 × 1.5 × 4 mm) loaded with 2 mg of bevacizumab was implanted subconjunctivally in three Dutch-belted pigmente...
Article
Glaucoma is a frequent and devastating long-term complication following ocular trauma, including corneal surgery, open globe injury, chemical burn, infection, etc. Post-event inflammation and neuroglial remodeling plays a key role in subsequent ganglion cell apoptosis and glaucoma. To this end, this study was designed to investigate the amplifying...
Article
This work addresses an unmet clinical need, that of glaucoma monitoring through intraocular pressure (IOP) interrogation in patients with artificial corneas (keratoprost hesis). We demonstrate direct integration of a low‐drift, fiber‐optic Fabry‐Perot pressure sensor embedded in the keratoprosthesis via rapid, non‐contact micromagnetic fiber alignm...
Article
Artificial cornea is an effective treatment of corneal blindness. Yet, intraocular pressure (IOP) measurements for glaucoma monitoring remain an urgent unmet need. Here, we present the integration of a fiber‐optic Fabry‐Perot pressure sensor with an FDA‐approved keratoprosthesis for real‐time IOP measurements using a novel strategy based on optical...
Preprint
Full-text available
Previous studies have suggested that microglia depletion using small molecule colony-stimulating factor 1 receptor (CSF1R) inhibitor, does not affect peripheral immune cells, and, therefore, disease phenotype changes are attributed to microglia depletion only. Here, we show that CSF1R inhibition by PLX5622 causes long-term changes in the myeloid an...
Article
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Inflammation plays an important role in pathological angiogenesis. Receptor-interacting protein 1 (RIP1) is highly expressed in inflammatory cells and is known to play an important role in the regulation of apoptosis, necroptosis, and inflammation; however, a comprehensive description of its role in angiogenesis remains elusive. Here, we show that...
Article
Purpose: To quantitatively analyze the angle anatomy in eyes with a Boston type 1 keratoprosthesis (KPro) using anterior segment optical coherence tomography (AS-OCT) and to assess the diagnostic ability of AS-OCT in KPro-associated glaucoma. Methods: AS-OCT (RTVue) images from KPro eyes with and without glaucoma were reviewed. The angle opening...
Article
Purpose: The most commonly applied prosthetic devices for corneal blindness in the setting of severe cicatricial keratoconjunctivitis are the Boston keratoprosthesis type II and the modified osteo-odonto-keratoprosthesis, with these requiring either normal eyelid skin or a healthy cuspid tooth, respectively. For patients with neither attribute, we...
Chapter
Purpose: To propose a modified treatment paradigm for chemical burns to the eye – in the acute and chronic phases – in particular aiming at preventing post-burn glaucoma. Methods: Recent laboratory and clinical data on the biology and treatment of severe chemical burns have been analyzed and organized for the cornea clinician. Results: Corneal blin...
Poster
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The magnetic levator prosthesis is a non-surgical magnetic eye wear device and lid adhesive to improve upon the age-old ptosis crutch. This presents preliminary data on a proprietary approach using angular translation of the spectacle magnet to provide adjustable force, and the use of custom designed 3-D printed frames based on craniofacial scans f...
Preprint
Full-text available
Inflammation plays an important role in pathologic angiogenesis. Receptor-interacting protein 1 (RIP1) is highly expressed in inflammatory cells and is known to play an important role in the regulation of apoptosis, necroptosis, and inflammation, however its role in angiogenesis remains elusive. Here, we show that RIP1 is abundantly expressed in in...
Article
Full-text available
Purpose: To review clinical aspects and cellular and molecular steps in the development of long-term glaucoma after corneal surgery or acute trauma-especially the pivotal role of tumor necrosis factor alpha (TNF-α), the rapidity of the secondary damage to the retinal ganglion cells, and the clinical promise of early antiinflammatory intervention....
Article
To address the shortcomings associated with corneal transplants, substantial efforts have been focused on developing new modalities such as xenotransplantion. Xenogeneic corneas are anatomically and biomechanically similar to the human cornea, yet their applications require prior decellularization to remove the antigenic components to avoid rejecti...
Article
Abstract Purpose To assess outcomes and glaucoma management in eyes with aniridia following Boston type 1 Keratoprosthesis (KPro) implantation. Design Retrospective, interventional comparative case series. Methods:Population Patients with aniridia and patients with other preoperative diagnoses (excluding Stevens-Johnson syndrome, mucous membrane...
Article
N-methyl-D-aspartate (NMDA)-induced excitotoxicity is an acute form of experimental retinal injury as a result of overactivation of glutamate receptors. NLRP3 (nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain containing-3) inflammasome, one of the most studied sensors of innate immunity, has been reported to play a cri...
Article
Purpose: Severe corneal disease contributes significantly to the global burden of blindness. Corneal allograft surgery remains the most commonly used treatment, but does not succeed long term in every patient, and the odds of success fall with each repeated graft. The Boston keratoprosthesis type I has emerged as an alternative to repeat corneal a...
Article
Parry‐Romberg syndrome is a hemifacial atrophy which can be complicated by melasma. We present two cases of Parry‐Romberg syndrome, treated by fat transfer and bleaching of the skin using a modified “Kligman's formula.” The atrophy, as well as the skin dyschromia, improved, and the results were stable.
Article
Purpose: Boston keratoprosthesis (KPro) patients are prone to glaucoma even with well-controlled intraocular pressure (IOP). Recent experimental data have shown that soluble tumor necrosis factor alpha (TNF-α) after ocular injury may contribute to progressive retinal damage and subsequent glaucoma. This study evaluates the blood plasma levels of so...
Article
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Reactive microglia and infiltrating peripheral monocytes have been implicated in many neurodegenerative diseases of the retina and CNS. However, their specific contribution in retinal degeneration remains unclear. We recently showed that peripheral monocytes that infiltrate the retina after ocular injury in mice become permanently engrafted into th...
Article
Full-text available
Previous studies have demonstrated that ocular injury can lead to prompt infiltration of bone-marrow–derived peripheral monocytes into the retina. However, the ability of these cells to integrate into the tissue and become microglia has not been investigated. Here we show that such peripheral monocytes that infiltrate into the retina after ocular i...
Preprint
Full-text available
Reactive microglia and infiltrating peripheral monocytes have been implicated in many neurodegenerative diseases of the retina and central nervous system (CNS). However, their specific contribution in retinal degeneration remains unclear. We recently showed that peripheral monocytes that infiltrate the retina after ocular injury become permanently...
Preprint
Full-text available
Previous studies have demonstrated that ocular injury can lead to prompt infiltration of bone marrow-derived peripheral monocytes into the retina. However, the ability of these cells to integrate into the tissue and become microglia has not been studied. Here we show that such peripheral monocytes not only infiltrate into the retina after ocular in...
Article
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Eyes that have suffered alkali burn to the surface are excessively susceptible to subsequent severe glaucoma and retinal ganglion cell loss, despite maximal efforts to prevent or slow down the disease. Recently, we have shown in mice and rabbits, that such retinal damage is neither mediated by the alkali itself reaching the retina nor by intraocula...
Article
Purpose: To systematically review the published literature on outcomes of Boston keratoprosthesis type 1 for the treatment of limbal stem cell deficiency secondary to severe chemical corneal injury. Methods: Literature searches were conducted in MEDLINE (Ovid), Embase, Web of Science, and the Cochrane Central Register. The main outcome measures...
Article
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Purpose: We further optimized and evaluated the safety of the magnetic levator prosthesis (MLP) for temporary management of severe blepharoptosis, and compared efficacy and comfort against the ptosis crutch. Methods: The interpalpebral fissure (IPF) of participants (n = 12) with ptosis was measured during attempted eyelid opening, volitional clo...
Data
Example of a left eye with early paracentral loss. Notes: The corresponding visual field test is shown in Figure 1 left side. The minimal BMO-MRW is 34.8 μm and the minimal sector BMO-MRW, as an average over three adjacent scans, is thicker at 92.4 μm. (A) Minimal BMO-MRW (34.8 μm) is in the inferotemporal sector (red arrow) on scan 6. (B) BMO-MRW...
Data
Diagram showing scans included in each sector for calculating sector BMO-MRW in a right eye. Notes: N: 10, 11, 12, 1, 2, 3, 4; SN: 5, 6, 7; ST: 8, 9, 10; T: 11, 12, 1, 2, 3; IT: 4, 5, 6; IN: 7, 8, 9. Similarly, the corresponding scans were used for calculating sector BMO-MRW in left eyes. Abbreviations: BMO-MRW, minimum rim width at Bruch’s membran...
Article
Full-text available
Purpose To compare optic nerve head (ONH) measurements in glaucomatous eyes with paracentral visual field (VF) loss to eyes with peripheral VF loss and controls. Methods Open-angle glaucoma (OAG) patients with early paracentral VF loss or isolated peripheral VF loss as well as control subjects underwent ONH imaging with swept-source optical cohere...
Article
Purpose To review the published literature on outcomes of keratolimbal allograft (KLAL) for the surgical treatment of limbal stem cell deficiency (LSCD) and corneal blindness after severe corneal chemical injury. Methods Literature searches were conducted in the following electronic databases: MEDLINE, EMBASE, Science Citation Index, CINAHL, LILAC...
Article
Purpose: To propose a new treatment paradigm for chemical burns to the eye - in the acute and chronic phases. Methods: Recent laboratory and clinical data on the biology and treatment of chemical burns are analyzed. Results: Corneal blindness from chemical burns can now be successfully treated with a keratoprosthesis, on immediate and intermed...
Article
Purpose: To compare structural features in prelaminar and laminar tissues of the optic nerve head (ONH) in chronic angle closure glaucoma (CACG), primary open angle glaucoma (POAG), and control subjects. Materials and Methods: ONH imaging was performed using swept-source optical coherence tomography (SS-OCT) for measurements of minimum rim width at...
Article
Purpose: To quantitatively evaluate the angle anatomy in eyes with the Boston type I keratoprosthesis (B-KPro) differing in the back plate (BP) material and size using anterior segment optical coherence tomography. Methods: B-KPro eyes with poly(methyl methacrylate) (PMMA) (7.0 and 8.5 mm) and titanium (7.0, 8.5, and 9.5 mm) BPs were imaged with...
Article
Alkali burns to the eye constitute a leading cause of worldwide blindness. In recent case series, corneal transplantation revealed unexpected damage to the retina and optic nerve in chemically burned eyes. We investigated the physical, biochemical, and immunological components of retinal injury after alkali burn and explored a novel neuroprotective...
Article
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Purpose Tumor necrosis factor (TNF)-α is upregulated in eyes following corneal alkali injury and contributes to corneal and also retinal damage. Prompt TNF-α inhibition by systemic infliximab ameliorates retinal damage and improves corneal wound healing. However, systemic administration of TNF-α inhibitors carries risk of significant complications,...
Poster
Full-text available
Purpose: To determine safety and feasibility of extended at home use of the magnetic levator prosthesis (MLP). For severe ptosis, non-surgical re-animation of the eyelid is possible with an N-52/PDMS micro-magnet array attached to the upper lid with hydocolloid-based medical adhesive and a larger secondary magnet embedded in a spectacle frame to li...
Article
Purpose of the study: The purpose of the study was to determine whether there are different patterns of retinal nerve fiber layer (RNFL) thinning as measured by spectral domain optical coherence tomography (SD-OCT) for 4 subtypes of open angle glaucoma (OAG): primary OAG (POAG), normal tension glaucoma (NTG), pseudoexfoliation glaucoma (PXG), and...
Chapter
The authors discuss the cause of eyelid bags, malar bags, and festoons that result from aging and loss of tissue elasticity. Conventional medications may be useful and a variety of surgeries have been recommended. The authors describe an alternative surgical approach for the correction of persistent malar bags that consists of liposuction and suspe...
Article
Aims To compare swept-source optical coherence tomography (SS-OCT) and enhanced depth imaging spectral-domain OCT (EDI-OCT) in quantitative assessment of optic nerve head (ONH) parameters. Methods In a cross-sectional study, patients with primary open angle glaucoma (POAG) and age-matched control subjects underwent SS-OCT and EDI-OCT B-scans of the...
Article
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Purpose: Titanium (Ti) is an excellent implantable biomaterial that can be further enhanced by surface topography optimization. Despite numerous data from orthopedics and dentistry, the effect of Ti surface topography on ocular cells is still poorly understood. In light of the recent adaptation of Ti in the Boston Keratoprosthesis artificial cornea...
Article
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Purpose: To compare the effects of post-penetrating keratoplasty (PK) and post-keratoprosthesis (KPro) surgery-related inflammation on the posterior segment of the eye and to assess inhibition of tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β) on these effects. Methods: BALB/C (syngeneic) or C57BL/6 (allogeneic) corneas were tr...
Article
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Purpose: To describe the fabrication, evaluation, and preliminary in vivo safety of a new drug delivery system (DDS) for topical anti-TNF-α antibody administration. Methods: A DDS was fabricated using inverse template fabrication of a hydrophobic three-dimensional porous scaffold (100-300 μm in diameter porosity) loaded with 10% polyvinyl alcoho...