Publications by authors named "Joseph B Ciolino"

65 Publications

CLEAR - Contact lens technologies of the future.

Cont Lens Anterior Eye 2021 Apr 25;44(2):398-430. Epub 2021 Mar 25.

School of Optometry and Vision Science, UNSW Sydney, Sydney, NSW, Australia.

Contact lenses in the future will likely have functions other than correction of refractive error. Lenses designed to control the development of myopia are already commercially available. Contact lenses as drug delivery devices and powered through advancements in nanotechnology will open up further opportunities for unique uses of contact lenses. This review examines the use, or potential use, of contact lenses aside from their role to correct refractive error. Contact lenses can be used to detect systemic and ocular surface diseases, treat and manage various ocular conditions and as devices that can correct presbyopia, control the development of myopia or be used for augmented vision. There is also discussion of new developments in contact lens packaging and storage cases. The use of contact lenses as devices to detect systemic disease has mostly focussed on detecting changes to glucose levels in tears for monitoring diabetic control. Glucose can be detected using changes in colour, fluorescence or generation of electric signals by embedded sensors such as boronic acid, concanavalin A or glucose oxidase. Contact lenses that have gained regulatory approval can measure changes in intraocular pressure to monitor glaucoma by measuring small changes in corneal shape. Challenges include integrating sensors into contact lenses and detecting the signals generated. Various techniques are used to optimise uptake and release of the drugs to the ocular surface to treat diseases such as dry eye, glaucoma, infection and allergy. Contact lenses that either mechanically or electronically change their shape are being investigated for the management of presbyopia. Contact lenses that slow the development of myopia are based upon incorporating concentric rings of plus power, peripheral optical zone(s) with add power or non-monotonic variations in power. Various forms of these lenses have shown a reduction in myopia in clinical trials and are available in various markets.
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http://dx.doi.org/10.1016/j.clae.2021.02.007DOI Listing
April 2021

Penetrating keratoplasty using collagen crosslinked donor tissue: A case report.

Am J Ophthalmol Case Rep 2021 Jun 24;22:101039. Epub 2021 Feb 24.

Massachusetts Eye and Ear Infirmary Boston, USA.

Purpose: In patients with corneal melt, pretreatment crosslinking (CXL) of donor tissue prior to placement of Boston keratoprosthesis (K-Pro I) decreases graft failure. We report a case of corneal sparing in a phthisical eye following penetrating keratoplasty (PKP) with pretreatment CXL of the donor cornea.

Observations: A 69-year-old female with a history of familial aniridia and bilateral K-Pro I placement. Her clinical course was complicated by recurrent corneal melt and hypotony in the left eye, resulting in extraction of the K-Pro I and successive PKP with pretreatment CXL of the donor cornea. She subsequently developed phthisis of the globe with notable retention of corneal structure. At 8 years, she maintains corneal contour without recurrence of keratolysis or extension of phthisis.

Conclusions And Importance: This is the first reported case of corneal sparing in a phthisical eye with a history of PKP, suggesting a protective role of pretreatment CXL of donor tissue against keratolysis and phthisis.
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http://dx.doi.org/10.1016/j.ajoc.2021.101039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930361PMC
June 2021

Nerve Growth Factor as an Ocular Therapy: Applications, Challenges, and Future Directions.

Semin Ophthalmol 2021 May 27;36(4):224-231. Epub 2021 Feb 27.

1. Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.

Nerve growth factor (NGF), the prototypical neurotrophin first discovered in the 1950s, has recently garnered increased interest as a therapeutic agent promoting neuronal health and regeneration. After gaining orphan drug status within the last decade, NGF-related research and drug development has accelerated. The purpose of this article is to review the preclinical and clinical evidence of NGF in various applications, including central and peripheral nervous system, skin, and ophthalmic disorders. We focus on the ophthalmic applications including not only the FDA-approved indication of neurotrophic keratitis but also retinal disease and glaucoma. NGF represents a promising therapy whose therapeutic profile is evolving. The challenges related to this therapy are reviewed, along with possible solutions and future directions.
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http://dx.doi.org/10.1080/08820538.2021.1890793DOI Listing
May 2021

Potential of Application of Iron Chelating Agents in Ophthalmic Diseases.

Semin Ophthalmol 2021 May 23;36(4):157-161. Epub 2021 Feb 23.

Ophthalmology, Associate Professor of Ophthalmology, Harvard Medical School Mass. Eye and Ear/Schepens Eye Research Institute, USA.

The investigations discussed in this review indicate that iron may exacerbate different eye diseases. Therefore, it is plausible that reducing cellular or body iron stores could influence disease pathogenesis, so it is logical to consider the iron chelators' potential protective role in the various ophthalmic diseases in the form of topical eye drops or slow releasing injectable compounds as an adjuvant treatment.
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http://dx.doi.org/10.1080/08820538.2021.1887900DOI Listing
May 2021

A Cluster of Corneal Donor Rim Cultures Positive for Achromobacter Species Associated With Contaminated Eye Solution.

Cornea 2021 Feb;40(2):223-227

Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA. Dr. André is now with Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, Université́ Claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Lyon, France.

Purpose: To investigate a cluster of corneoscleral rim cultures positive for Achromobacter species over a 6-month period at Massachusetts Eye and Ear.

Methods: An increased rate of positive corneal donor rim cultures was noted at Massachusetts Eye and Ear between July and December 2017. Positive cultures were subjected to identification and antimicrobial susceptibility testing by phenotypic (MicroScan WalkAway) and genotypic (16S rDNA sequencing) methods. Samples of the eye wash solution (GeriCare) used in the eye bank were also evaluated. Antimicrobial activity of Optical-GS against Achromobacter spp. at 4°C and 37°C was assessed by time-kill kinetics assay.

Results: Of 99 donor rims cultured, 14 (14.1%) grew bacteria with 11 (78.6%) due to uncommon nonfermenting Gram-negative bacilli. These had been identified by standard automated methods as Achromobacter (n = 3), Alcaligenes (n = 3), Ralstonia (n = 2), Pseudomonas (n = 2), and Stenotrophomonas (n = 1). Eight of these 11 isolates were subsequently available for molecular identification, and all were identified as Achromobacter spp. Six bottles of eyewash solution were evaluated and were positive for abundant Achromobacter spp. (3.4 × 105 ± 1.1 CFU/mL). Optisol-GS had no bactericidal activity against Achromobacter spp. at 4°C after 24-hour incubation but was bactericidal at 37°C. None of the patients who had received the contaminated corneas developed postoperative infection.

Conclusions: An eyewash solution arising from a single lot was implicated in the contamination of donor rims by Achromobacter spp. The isolates were able to survive in the Optisol-GS medium at the recommended storage temperature. This highlights the need to continue improving protocols for tissue preparation and storage.
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http://dx.doi.org/10.1097/ICO.0000000000002473DOI Listing
February 2021

Methods for Investigating Corneal Cell Interactions and Extracellular Vesicles In Vitro.

Curr Protoc Cell Biol 2020 12;89(1):e114

Schepens Eye Research Institute of Massachusetts Eye and Ear and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.

Science and medicine have become increasingly "human-centric" over the years. A growing shift away from the use of animals in basic research has led to the development of sophisticated in vitro models of various tissues utilizing human-derived cells to study physiology and disease. The human cornea has likewise been modeled in vitro using primary cells derived from corneas obtained from cadavers or post-transplantation. By utilizing a cell's intrinsic ability to maintain its tissue phenotype in a pre-designed microenvironment containing the required growth factors, physiological temperature, and humidity, tissue-engineered corneas can be grown and maintained in culture for relatively long periods of time on the scale of weeks to months. Due to its transparency and avascularity, the cornea is an optimal tissue for studies of extracellular matrix and cell-cell interactions, toxicology and permeability of drugs, and underlying mechanisms of scarring and tissue regeneration. This paper describes methods for the cultivation of corneal keratocytes, fibroblasts, epithelial, and endothelial cells for in vitro applications. We also provide detailed, step-by-step protocols for assembling and culturing 3D constructs of the corneal stroma, epithelial- and endothelial-stromal co-cultures and isolation of extracellular vesicles. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Isolating and culturing human corneal keratocytes and fibroblasts Basic Protocol 2: Isolating and culturing human corneal epithelial cells Basic Protocol 3: Isolating and culturing human corneal endothelial cells Basic Protocol 4: 3D corneal stromal construct assembly Basic Protocol 5: 3D corneal epithelial-stromal construct assembly Basic Protocol 6: 3D corneal endothelial-stromal construct assembly Basic Protocol 7: Isolating extracellular vesicles from corneal cell conditioned medium Support Protocol: Cryopreserving human corneal fibroblasts, corneal epithelial cells, and corneal endothelial cells.
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http://dx.doi.org/10.1002/cpcb.114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596691PMC
December 2020

A randomized, sham-controlled trial of intraductal meibomian gland probing with or without topical antibiotic/steroid for obstructive meibomian gland dysfunction.

Ocul Surf 2020 10 31;18(4):852-856. Epub 2020 Aug 31.

Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; Center for Translational Ocular Immunology, USA; Cornea Service, New England Eye Center, And Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA. Electronic address:

Importance: Obstructive meibomian gland dysfunction (MGD) can be refractory to medical therapy. Intraductal meibomian gland (MG) probing may offer a potential therapeutic approach for these patients, but no randomized trials have been conducted to date.

Objective: To assess clinical changes after intraductal MG probing for patients with refractory obstructive meibomian gland dysfunction.

Design: Randomized, double-masked, sham-controlled clinical trial.

Setting: Single-center, tertiary referral center.

Participants: 42 patients with refractory obstructive MGD associated with lid tenderness.

Interventions: Enrolled patients received one of the following treatments: 1) MG probing plus post-procedural topical sulfacetamide/prednisolone ointment (Blephamide®), 2) MG probing plus post-procedural lubricating ointment (GenTeal), or 3) sham probing plus GenTeal ointment. The probing was performed on the upper lids of both eyes.

Main Outcome Measures: Primary outcome measures were symptoms as measured by Ocular Surface Disease Index (OSDI) and Symptom Assessment iN Dry Eye (SANDE), as well as tear break-up time (TBUT). Secondary outcome measures were other clinical signs. Safety of the procedure was also evaluated by investigating the treatment-related adverse events. At baseline and 4 weeks after the procedure a masked observer evaluated the following outcome measures: symptom questionnaires, including OSDI and SANDE, upper lid tenderness, lid margin telangiectasia, corneal fluorescein staining, conjunctival lissamine green staining, TBUT, Schirmer's test, and meibomian glands yielding liquid secretion (MGYLS).

Results: Compared to baseline, the MG probing/Blephamide® group showed significant improvements in both OSDI and SANDE scores and the MG probing/GenTeal group demonstrated a significant improvement only in SANDE score. In contrast, the Sham/GenTeal group did not show any statistically significant changes in symptoms. There were no statistically significant changes in clinical signs in any group at the 4-week visit, except for improvement of lid tenderness in the sham probing group.

Conclusions: MG probing/Blephamide® results in a significant improvement in symptoms in patients with refractory obstructive MGD without any significant effect on clinical signs. Larger studies are warranted to determine the efficacy of MG probing.

Trial Registration: Clinicaltrials.gov(identifier NCT02256969, Filed on 08/13/2014).
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http://dx.doi.org/10.1016/j.jtos.2020.08.008DOI Listing
October 2020

Steroid-eluting contact lenses for corneal and intraocular inflammation.

Acta Biomater 2020 10 16;116:149-161. Epub 2020 Aug 16.

Department of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute at Massachusetts Eye & Ear, 325 Charles Street, Boston 02114, MA, United States. Electronic address:

Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo (rabbit model). In an ocular irritation study (Draize test) with Dex-Lens extracts, no adverse events were observed in normal rabbit eyes. Dex-Lenses effectively inhibited suture-induced corneal neovascularization and inflammation for 7 days and lipopolysaccharide-induced anterior uveitis for 5 days. The efficacy of Dex-Lenses was similar to that of hourly-administered dexamethasone eye drops. In the corneal neovascularization study, substantial corneal edema was observed in rabbit eyes that received no treatment and those that wore a vehicle lens as compared to rabbit eyes that wore the Dex-Lens. Throughout these studies, Dex-Lenses were well tolerated and did not exhibit signs of toxicity. Dexamethasone-eluting contact lenses may be an option for the treatment of ocular inflammation and a platform for ocular drug delivery. STATEMENT OF SIGNIFICANCE: Inflammation of the eye can happen either on the ocular surface (i.e. the cornea) or inside the eye, both of which can result in loss of vision or even blindness. Ocular inflammation is normally treated by steroid eye drops. Depending on the type and severity of inflammation, patients may have to take drops every hour for days at a time. Such severe dosing regimen can lead to patients missing doses. Also, more than 95% drug in an eye drop never goes inside the eye. Here we present a contact lens that release a steroid (dexamethasone) for seven days at a time. It is much more efficient than eye drops and a significant improvement since once worn, the patient will avoid missing doses.
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http://dx.doi.org/10.1016/j.actbio.2020.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040324PMC
October 2020

One-Year Clinical Outcomes of Preloaded Descemet Membrane Endothelial Keratoplasty Versus Non-Preloaded Descemet Membrane Endothelial Keratoplasty.

Cornea 2021 Mar;40(3):311-319

Department of Ophthalmology, Harvard Medical School, Schepens Eye Research Institution, Massachusetts Eye and Ear Infirmary, Boston, MA.

Purpose: To compare the one-year outcomes of preloaded Descemet membrane endothelial keratoplasty (pDMEK) and non-preloaded DMEK (n-pDMEK) in patients with Fuchs endothelial corneal dystrophy (FECD).

Methods: This retrospective comparative cohort study consecutively included 68 eyes with Fuchs endothelial corneal dystrophy who underwent either pDMEK (n = 38) or n-pDMEK (n = 30) performed by cornea fellows with an experienced surgeon between 2016 and 2018 at the Massachusetts Eye and Ear Infirmary. Exclusion criteria were previous surgery (other than uncomplicated cataract surgery) and any documented evidence of macular or other corneal diseases. Corrected distance visual acuity (CDVA), central corneal thickness, intraocular pressure, patient characteristics, postprocessing endothelial cell count, donor graft data, and complications were compared.

Results: CDVA showed similar results for pDMEK (0.12 ± 0.11 logarithm of the minimal angle of resolution [LogMAR]) and n-pDMEK (0.13 ± 0.13 LogMAR) (P = 0.827). Sixty-six percent of the pDMEK eyes and 57% of the n-pDMEK eyes achieved a VA of ≥0.1 LogMAR, and 95% and 97%, respectively, achieved a CDVA ≥0.3 LogMAR. The preoperative central corneal thickness of pDMEK and n-pDMEK (644 ± 62.2 μm, 660.5 ± 56.2 μm) decreased significantly after surgery (525.1 ± 43.6 μm, 526.5 ± 45.2 μm, P < 0.001), with no difference between groups (P = 0.840). The postprocessing endothelial cell count did not differ between pDMEK (2959.2 ± 182.9 cells/mm2) and n-pDMEK (2939.3 ± 278.7 cells/mm2) (P = 0.484). Complication rates were comparable with just the rebubbling performed in a minor procedure room showing a lower rate for pDMEK (13.16%) compared with n-pDMEK (33.33%) (P < 0.045).

Conclusions: One-year clinical outcomes were similar between pDMEK and n-pDMEK procedures, rendering eye bank-prepared pDMEK tissues a useful tool in the treatment of endothelial dysfunction.
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http://dx.doi.org/10.1097/ICO.0000000000002430DOI Listing
March 2021

Extracellular Vesicles Secreted by Corneal Epithelial Cells Promote Myofibroblast Differentiation.

Cells 2020 04 26;9(5). Epub 2020 Apr 26.

Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.

The corneal epithelium mediates the initial response to injury of the ocular surface and secretes a number of profibrotic factors that promote corneal scar development within the stroma. Previous studies have shown that corneal epithelial cells also secrete small extracellular vesicles (EVs) in response to corneal wounding. In this paper, we hypothesized that EVs released from corneal epithelial cells in vitro contain protein cargo that promotes myofibroblast differentiation, the key cell responsible for scar development. We focused on the interplay between corneal epithelial-derived EVs and the stroma to determine if the corneal fibroblast phenotype, contraction, proliferation, or migration were promoted following vesicle uptake by corneal fibroblasts. Our results showed an increase in myofibroblast differentiation based on α-smooth muscle actin expression and elevated contractility following EV treatment compared to controls. Furthermore, we characterized the contents of epithelial cell-derived EVs using proteomic analysis and identified the presence of provisional matrix proteins, fibronectin and thrombospondin-1, as the dominant encapsulated protein cargo secreted by corneal epithelial cells in vitro. Proteins associated with the regulation of protein translation were also abundant in EVs. This paper reveals a novel role and function of EVs secreted by the corneal epithelium that may contribute to corneal scarring.
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http://dx.doi.org/10.3390/cells9051080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290736PMC
April 2020

Keratoconus progression associated with hormone replacement therapy.

Am J Ophthalmol Case Rep 2019 Sep 16;15:100519. Epub 2019 Jul 16.

Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.

Purpose: To report a postmenopausal patient with keratoconus who experienced significant progression after using hormone replacement therapy.

Observations: A 51-year-old woman with previously stable keratoconus presented with acute disease progression following hormone replacement therapy in the context of prophylactic hysterectomy and bilateral ovariosalpingectomy. Over a 14-month period after starting hormone therapy, the steepest K increased from 63.7D to 71.5D in the right eye and from 65.8D to 78.1D in the left eye.

Conclusions: Hormone replacement therapy may amplify progression of keratoconus.
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http://dx.doi.org/10.1016/j.ajoc.2019.100519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656926PMC
September 2019

Topical sustained drug delivery to the retina with a drug-eluting contact lens.

Biomaterials 2019 10 21;217:119285. Epub 2019 Jun 21.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Intravitreal injections and implants are used to deliver drugs to the retina because therapeutic levels of these medications cannot be provided by topical administration (i.e. eye drops). In order to reach the retina, a topically applied drug encounters tear dilution, reflex blinking, and rapid fluid drainage that collectively reduce the drug's residence time on the ocular surface. Residing under the tears, the cornea is the primary gateway into the eye for many topical ophthalmic drugs. We hypothesized that a drug-eluting contact lens that rests on the cornea would therefore be well-suited for delivering drugs to the eye including the retina. We developed a contact lens based dexamethasone delivery system (Dex-DS) that achieved sustained drug delivery to the retina at therapeutic levels. Dex-DS consists of a dexamethasone-polymer film encapsulated inside a contact lens. Rabbits wearing Dex-DS achieved retinal drug concentrations that were 200 times greater than those from intensive (hourly) dexamethasone drops. Conversely, Dex-DS demonstrated lower systemic (blood serum) dexamethasone concentrations. In an efficacy study in rabbits, Dex-DS successfully inhibited retinal vascular leakage induced by intravitreal injection of vascular endothelial growth factor (VEGF). Dex-DS was found to be safe in a four-week repeated dose biocompatibility study in healthy rabbits.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119285DOI Listing
October 2019

Oral guaifenesin for treatment of filamentary keratitis: A pilot study.

Ocul Surf 2019 07 1;17(3):565-570. Epub 2019 Apr 1.

Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. Electronic address:

Purpose: Pilot study to evaluate the safety and efficacy of oral guaifenesin in reducing the signs and symptoms of filamentary keratitis.

Methods: Prospective, uncontrolled open-label pilot study. Twelve patients with non-Sjögren dry eye disease (DED) and secondary filamentary keratitis received treatment with oral guaifenesin 600 mg twice a day (total dose of 1.2 g/day) for 4 weeks. Adverse events, change in the number of corneal filaments, corneal fluorescein staining (CFS; NEI grading system), and symptoms (Ocular Surface Disease Index) were assessed.

Results: Before starting oral guaifenesin, all patients were on topical medical therapy for their condition. At baseline, the mean number of filaments was 5.8 ± 2.9, CFS score 7.3 ± 3.2, and OSDI score 55.6 ± 25. After 4 weeks of treatment, the number of filaments was 2.1 ± 2.2 (p = 0.04 vs. baseline), CFS score 6.5 ± 3.1 (p = 0.5), and OSDI score 46.1 ± 30.9 (p = 0.2). One patient discontinued the medication due to gastrointestinal side effects.

Conclusions: Oral guaifenesin was safe and generally well tolerated, and demonstrated modest efficacy in reducing the severity of filamentary keratitis. These results should be considered preliminary; however, placebo-controlled investigations would be justified to evaluate the therapeutic efficacy of oral guaifenesin as a mucolytic in treatment of filamentary keratitis.
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http://dx.doi.org/10.1016/j.jtos.2019.03.008DOI Listing
July 2019

A Clinical Phase II Study to Assess Efficacy, Safety, and Tolerability of Waterfree Cyclosporine Formulation for Treatment of Dry Eye Disease.

Ophthalmology 2019 06 28;126(6):792-800. Epub 2019 Jan 28.

Novaliq GmbH, Heidelberg, Germany. Electronic address:

Purpose: To compare the efficacy, safety, and tolerability of waterfree cyclosporine formulation (CyclASol) at 2 concentrations (0.1% and 0.05% of cyclosporine [CsA]) to vehicle when applied twice daily for 16 weeks in patients with dry eye disease (DED). An open-label Restasis (Allergan, Irvine, CA) arm was included to allow a direct comparison with an approved therapy.

Design: An exploratory phase II, multicenter, randomized, vehicle-controlled clinical trial, double-masked between CyclASol and vehicle with an open-label comparator.

Participants: Two hundred and seven eligible patients with a history of dry eye disease were randomized 1:1:1:1 to 1 of 4 treatment arms (CyclASol 0.05%, n = 51; CyclASol 0.1%, n = 51; vehicle, n = 52, and Restasis, n = 53).

Methods: After a 2-week run-in period with twice-daily dosing of Systane Balance (Alcon, Fort Worth, TX), patients were randomized to the respective treatment arm and dosed twice daily for 16 weeks.

Main Outcome Measures: The study was set up to explore efficacy on a number of sign and symptom end points including total and subregion corneal fluorescein staining, conjunctival staining, visual analog scale (VAS) for dry eye symptoms VAS severity, and Ocular Surface Disease Index (OSDI) questionnaire.

Results: CyclASol showed a consistent reduction in corneal and conjunctival staining compared with both vehicle and Restasis over the 16-week treatment period, with an early onset of effect (at day 14). A mixed-effects model-based approach demonstrated that the CyclASol drug effect was statistically significant over vehicle (total corneal staining P < 0.1, central corneal staining P < 0.001, conjunctival staining P < 0.01). This model-based analysis suggests a significant CyclASol effect for OSDI as symptom parameter (P < 0.01). The numbers of ocular adverse events were low in all treatment groups.

Conclusions: CyclASol showed efficacy, safety, and tolerability at 2 concentrations in moderate-to-severe DED. In a direct head-to-head against open-label Restasis, CyclASol was found to have an earlier onset of action, as early as after 2 weeks of treatment, in relieving the signs of DED, as measured by corneal and conjunctival staining. The central region of the cornea, an important area for visual function in dry eye sufferers, was shown to have the most benefit from treatment. Excellent safety, tolerability, and comfort profile supports this new CsA formulation as having a positive benefit-to-risk ratio.
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http://dx.doi.org/10.1016/j.ophtha.2019.01.024DOI Listing
June 2019

Transepithelial versus epithelium-off corneal crosslinking for corneal ectasia.

J Cataract Refract Surg 2018 Dec 9;44(12):1507-1516. Epub 2018 Oct 9.

From the Schepens Eye Research Institute (Kobashi), Department of Ophthalmology, Harvard Medical School, Boston, and the Massachusetts Eye and Ear Infirmary (Rong, Ciolino), Harvard Medical School, Boston, Massachusetts, USA the Department of Ophthalmology (Kobashi), Keio University, School of Medicine, Tokyo, Japan.

This review compared the clinical results of transepithelial corneal crosslinking (CXL) to epithelium-off (epi-off) CXL in progressive corneal ectasia using a metaanalysis. The Cochrane databases and Medline were searched for randomized controlled trials (RCTs). Seven RCTs involving 505 eyes that met the eligibility criteria were identified. The epi-off CXL group showed significantly better outcomes in postoperative changes in maximum keratometry (K) during 1-year observation periods. Transepithelial CXL resulted in significantly greater post-treatment central corneal thickness and best spectacle-corrected visual acuity (BSCVA). The presence of a postoperative demarcation line was significantly more frequent after epi-off CXL than that after transepithelial CXL. No statistically significant difference was found between other parameters. Although patients in the transepithelial CXL group demonstrated a greater improvement in BSCVA compared with patients in the epi-off CXL group at the 1 year follow-up, transepithelial CXL had less impact on halting progressive corneal ectasia in terms of maximum K than epi-off CXL.
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http://dx.doi.org/10.1016/j.jcrs.2018.08.021DOI Listing
December 2018

Resolution of fluoroquinolone-resistant keratitis with a PROSE device for enhanced targeted antibiotic delivery.

Am J Ophthalmol Case Rep 2018 Dec 12;12:73-75. Epub 2018 Sep 12.

Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, USA.

Purpose: To report the resolution of a fluoroquinolone-resistant keratitis with use of a prosthetic replacement of the ocular surface ecosystem (PROSE) device for enhanced targeted delivery of moxifloxiacin.

Observations: A 62-year-old female presented with a 3-day history of pain, photophobia, and declining vision in left eye. The patient had a 2-year history of binocular PROSE treatment for ocular chronic graft-vs-host disease (cGVHD). A corneal ulcer was diagnosed and treated with topical 0.5% moxifloxacin solution 6 times per day, with continued wear of the PROSE device. After 4 days, worsening symptoms led to an increase in application of moxifloxicin to every 2 hours while awake. The drug was administered by removal of the device, cleaning and replenishing the reservoir with sterile saline, and adding one drop of the drug to the reservoir prior to reinsertion. Four days later, the corneal surface was epithelialized with only small subepithelial infiltrate remaining. The corneal culture grew an isolate carrying multiple mutations in the topoisomerase genes. These mutations were correlated with varying levels of resistance to ciprofloxacin (256 μg/mL), levofloxacin (8 μg/mL), and moxifloxacin (16 μg/mL).

Conclusions And Importance: Although the infecting strain exhibited resistance to fluoroquinolones, the infection resolved when moxifloxacin was combined with PROSE therapy. Frequent dosing to the PROSE reservoir is likely to increase fluoroquinolone bioavailability and may represent a valuable approach to overcome antibiotic resistance.
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http://dx.doi.org/10.1016/j.ajoc.2018.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159334PMC
December 2018

Innovative Development of Contact Lenses.

Cornea 2018 Nov;37 Suppl 1:S94-S98

Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA.

Contact lenses have been a common means of vision correction for more than half a century. Recent developments have raised the possibility that the next few decades will see a considerable broadening of the range of applications for contact lenses, with associated expansions in the number and type of individuals who consider them a valuable option. The novel applications of contact lenses include treatment platforms for myopic progression, biosensors, and ocular drug delivery. Orthokeratology has shown the most consistent treatment for myopia control with the least side effects. Recent work has resulted in commercialization of a device to monitor intraocular pressure for up to 24 hours, and extensive efforts are underway to develop a contact lens sensor capable of continuous glucose tear film monitoring for the management of diabetes. Other studies on drug-eluting contact lenses have focused on increasing the release duration through molecular imprinting, use of vitamin E, and increased drug binding to polymers by sandwiching a poly (lactic-co-glycolic acid) layer in the lens. This review demonstrates the potential for contact lenses to provide novel opportunities for refractive management, diagnosis, and management of diseases.
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http://dx.doi.org/10.1097/ICO.0000000000001725DOI Listing
November 2018

Outcomes of Boston keratoprosthesis type 1 reimplantation: multicentre study results.

Can J Ophthalmol 2018 06 11;53(3):284-290. Epub 2017 Dec 11.

Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA. Electronic address:

Objective: To investigate the visual and anatomical outcomes of Boston keratoprosthesis (Kpro) type 1 reimplantation.

Design: Subgroup analysis of multicentre prospective cohort study.

Participants: Of 303 eyes that underwent Kpro implantation between January 2003 and July 2008 by 1 of 19 surgeons at 18 medical centres, 13 eyes of 13 patients who underwent reimplantation of Boston Kpro type 1 were compared with 13 eyes of 13 diagnosis-matched patients who underwent initial implantation.

Methods: Forms reporting preoperative, intraoperative, and postoperative parameters were prospectively collected and analyzed. Main outcome measures were Kpro retention and logMAR visual acuity.

Results: After a mean follow-up time of 17.1 ± 17.6 months, the retention of both initial and repeat Kpro implantation was 92.3% (12/13 in both groups), and 62% of initial implantation and 58% of repeat implantation eyes achieved visual acuity better than 20/200. Vision worse than 20/200 was often due to glaucoma or posterior segment pathology. Best-recorded logMAR visual acuity was significantly improved postoperatively in both groups (p < 0.001), and there was no statistically significant difference in final logMAR visual acuity between the 2 groups (p = 0.89). Sterile keratolysis (n = 4) and fungal infection (n = 5) were the most common causes of initial Kpro failure in the repeat Kpro group. The single failure in the repeat Kpro implantation group was due to fungal keratitis, and in the control group it was related to Kpro extrusion.

Conclusions: Repeat Kpro implantation is a viable option after failed initial Kpro, with visual and anatomical outcomes comparable to those of initial procedures.
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http://dx.doi.org/10.1016/j.jcjo.2017.10.021DOI Listing
June 2018

Brimonidine Ophthalmic Solution 0.025% for Reduction of Ocular Redness: A Randomized Clinical Trial.

Optom Vis Sci 2018 03;95(3):264-271

Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts

Significance: The α2-adrenergic receptor agonist brimonidine has been reported to induce conjunctival blanching in cataract, strabismus, laser refractive, and filtration procedures. Clinicians are often faced with red eyes with no apparent underlying pathology. Low-dose brimonidine reduced ocular redness in such subjects with efficacy maintained over 1 month and negligible rebound redness.

Purpose: The aim of this study was to evaluate the safety and efficacy of brimonidine tartrate ophthalmic solution 0.025% for the treatment of ocular redness.

Methods: In this single-center, double-masked, phase 3 clinical trial, adult subjects with baseline redness of more than 1 unit in both eyes (0- to 4-unit scale) were randomized 2:1 to brimonidine 0.025% or vehicle. A single dose was administered in-office (day 1); thereafter subjects instilled treatment four times a day for 4 weeks, with clinic visits on days 15, 29, and 36 (7 days post-treatment). Efficacy end points included investigator-evaluated redness 5 to 240 minutes post-instillation on day 1 (primary); investigator-evaluated change from baseline 1, 360, and 480 minutes post-instillation on day 1, and 1 and 5 minutes post-instillation on days 15 and 29; total clearance of redness, and subject-assessed redness. Safety/tolerability measures included adverse events, rebound redness, and drop comfort.

Results: Sixty subjects were randomized (n = 40 brimonidine, n = 20 vehicle). Investigator-assessed redness was lower with brimonidine versus vehicle over the 5- to 240-minute post-instillation period (mean [SE], 0.62 [0.076] vs. 1.49 [0.108]; P < .0001) and at each time point within that period (P < .0001). At 1, 360, and 480 minutes post-instillation, respectively, the mean differences (95% confidence interval) between treatments were -0.73 (-1.05 to -0.41), -0.57 (-0.84 to -0.29), and -0.39 (-0.67 to -0.10), respectively. No tachyphylaxis was evident with brimonidine on days 15 and 29, and minimal rebound redness was observed following discontinuation. Adverse events were infrequent, and brimonidine was rated as very comfortable.

Conclusions: Brimonidine 0.025% appeared safe and effective for reduction of ocular redness, with an 8-hour duration of action, no evidence of tachyphylaxis, and negligible rebound redness.
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http://dx.doi.org/10.1097/OPX.0000000000001182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839712PMC
March 2018

Corneal Cross-Linking With Verteporfin and Nonthermal Laser Therapy.

Cornea 2018 Mar;37(3):362-368

Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA.

Purpose: To test whether verteporfin with a nonthermal laser increases corneal mechanical stiffness and resistance to enzymatic degradation ex vivo.

Methods: Thirty human corneas (n = 5 per group) were treated with verteporfin alone (V), irradiated with nonthermal laser therapy (689 nm) alone (NTL), or received combined treatment of verteporfin with nonthermal laser therapy for 1 sequence (V+NTL1) or 6 sequences (V+NTL6) of 1 minute of NTL exposure. Positive controls were pretreated with 0.1% riboflavin/20% dextran every 3 to 5 minutes for 30 minutes and irradiated with ultraviolet light type A (λ = 370 nm, irradiance = 3 mW/cm) for 30 minutes using the Dresden protocol (R+UVA). Untreated corneas were used as negative controls. The corneal biomechanical properties were measured with enzymatic digestion, compression, creep, and tensile strength testing.

Results: V+NTL6- and R+UVA-treated corneas acquired higher rigidity and more pronounced curvature than untreated corneas. The stress-strain tests showed that V+NTL6 and R+UVA corneas became significantly stiffer than controls (P < 0.005). The V+NTL6 group seemed to be slightly stiffer than the R+UVA group, although the differences were not statistically significant. V+NTL6 corneas were found to have a significantly lower absolute creep rate (-1.87 vs. -3.46, P < 0.05) and significantly higher maximum stress values (7.67 vs. 3.02 P < 0.05) compared with untreated corneas.

Conclusions: Verteporfin-NTL (V+NTL6) increases corneal mechanical stiffness and resistance to enzymatic collagenase degradation. Although a clinical study is needed, our results suggest that V+NTL6 induces corneal cross-linking and corneal biomechanical changes that are similar to those induced by standard corneal collagen cross-linking.
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http://dx.doi.org/10.1097/ICO.0000000000001473DOI Listing
March 2018

Chemical Burns of the Eye: The Role of Retinal Injury and New Therapeutic Possibilities.

Cornea 2018 Feb;37(2):248-251

Cornea Service and Boston Keratoprosthesis Laboratory, Massachusetts Eye and Ear Infirmary and Schepens Eye Research Institute, Harvard Medical School, Boston, MA.

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 intermediate bases. Long term outcomes, however, are hampered by early retinal damage causing glaucoma. New data suggest that rapid diffusion of inflammatory cytokines posteriorly (TNF-α, etc) can severely damage the ganglion cells. Prompt anti-TNF-α treatment is markedly neuroprotective. Long term profound reduction of the intraocular pressure is also vital.

Conclusion: A new regimen, in addition to standard treatment, for severe chemical burns is proposed. This involves tumor necrosis factor alpha (TNF-α) inhibition promptly after the accident (primarily for retinal neuroprotection), prophylactic maximal lowering of the intraocular pressure (starting immediately), and keratoprosthesis implantation in a later quiet state.
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http://dx.doi.org/10.1097/ICO.0000000000001438DOI Listing
February 2018

Evaluation of a new artificial tear formulation for the management of tear film stability and visual function in patients with dry eye.

Clin Ophthalmol 2017 19;11:1883-1889. Epub 2017 Oct 19.

Andover Eye Clinic, Andover MA.

Purpose: Artificial tears are the first line of therapy for dry eye disease (DED) and are also the most frequently used treatment approach for this common condition. Despite this, there are few published studies that directly compare the effectiveness of different drop preparations, especially those formulated specifically for dry eye. In this study, we tested a new artificial tear product, Rohto Dry-Aid™, for its ability to relieve the signs and symptoms of DED. The study used a second drop, Systane Ultra, as a positive comparator.

Materials And Methods: This was a prospective, single-center, open-label, parallel-group study comparing the effects of the two products when used continuously over ~30 days (Clinical Trials registration number NCT03183089). Subjects were randomly assigned to one of the two test groups and were monitored 2 and 4 weeks after enrollment. Efficacy endpoints included ocular staining, visual function, and ocular discomfort.

Results: Treatment groups had similar ocular staining and ocular comfort scores, and both showed statistically significant ocular discomfort score improvement. Subjects in the Rohto group reported significant improvements in visual tasking activities such as watching television and driving at night. There was also a tendency for diary symptom scores to worsen from morning to evening in the Systane group, but not in the Rohto group; this trend was not significant, but warrants further study.

Conclusion: The two products, Rohto Dry-Aid and Systane Ultra, elicited comparable effects on the signs and symptoms of DED. While both products are designed to provide long-lasting relief, subjects in the Rohto group experienced a superior relief from discomfort associated with visual tasking activities and daily diaries, indicating that the Rohto drops may provide a longer duration of symptomatic relief over the course of the day.
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http://dx.doi.org/10.2147/OPTH.S144369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656345PMC
October 2017

TFOS DEWS II Clinical Trial Design Report.

Ocul Surf 2017 07 20;15(3):629-649. Epub 2017 Jul 20.

School of Optometry and Vision Science, UNSW Australia, Sydney, NSW, Australia.

The development of novel therapies for Dry Eye Disease (DED) is formidable, and relatively few treatments evaluated have been approved for marketing. In this report, the Subcommittee reviewed challenges in designing and conducting quality trials, with special reference to issues in trials in patients with DED and present the regulatory perspective on DED therapies. The Subcommittee reviewed the literature and while there are some observations about the possible reasons why so many trials have failed, there is no obvious single reason other than the lack of correlation between signs and symptoms in DED. Therefore the report advocates for conducting good quality studies, as described, going forward. A key recommendation for future studies is conduct consistent with Good Clinical Practice (GCP), including use of Good Manufacturing Practice (GMP) quality clinical trial material. The report also recommends that the design, treatments, and sample size be consistent with the investigational treatment, the objectives of the study, and the phase of development. Other recommendations for pivotal studies are a priori selection of the outcome measure, and an appropriate sample size.
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http://dx.doi.org/10.1016/j.jtos.2017.05.009DOI Listing
July 2017

Ex Vivo Study of Transepithelial Corneal Cross-linking.

J Refract Surg 2017 Mar;33(3):171-177

Purpose: To perform in vitro assessment of different techniques of transepithelial corneal cross-linking (CXL) and to compare the results to deepithelialized CXL.

Methods: Transepithelial CXL was performed after pre-treatment with or without penetration enhancers (gum cellulose, 0.44% sodium chloride, and 0.01% benzalkonium chloride) for 15 or 60 minutes. Deepithelialized corneas underwent CXL after pretreatment with riboflavin for 15 minutes, according to the Dresden protocol. All corneas were incubated in 0.3% collagenase A solution and the time to total dissolution was measured. Corneas were also imaged with confocal microscopy to evaluate the corneal epithelium, subbasal nerve plexus, and depth of stromal keratocyte nuclei as a means of measuring the depth of collagen CXL.

Results: Deepithelialized CXL corneas with 15 minutes of pretreatment dissolved after 15.4 ± 3.1 hours, significantly longer (P = .001) than deepithelialized untreated corneas (8.5 ± 0.6 hours). Transepithelial CXL corneas with 15 minutes of pretreatment with or without penetration enhancers dissolved after 8.3 ± 2.1 and 7.4 ± 1.6 hours, respectively. A longer pretreatment of 60 minutes with penetration enhancers resulted in greater resistance to degradation of the transepithelial CXL corneas (14.6 ± 2.2 hours), which was similar to deepithelialized CXL corneas. The results of the biological assay correlated well with the imaging results obtained by confocal microscopy.

Conclusions: Corneas treated by transepithelial CXL with an extended pretreatment time of 60 minutes and penetration enhancers exhibited similar characteristics as corneas treated by the deepithelialized CXL approach. By confocal imaging, the transepithelial approach with extended pretreatment time demonstrated evidence of epithelial damage, which may have improved the treatment effect of this group. [J Refract Surg. 2017;33(3):171-177.].
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http://dx.doi.org/10.3928/1081597X-20161206-04DOI Listing
March 2017

Corneal Resistance to Keratolysis After Collagen Crosslinking With Rose Bengal and Green Light.

Invest Ophthalmol Vis Sci 2016 12;57(15):6610-6614

Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States.

Purpose: The purpose of this study was to evaluate the resistance to degradation by collagenase A of corneas that have been crosslinked with Rose Bengal and green light (RGX).

Methods: The ex vivo crosslinking procedure was performed on enucleated rabbit corneas. Corneas were deepithelialized after applying 30% alcohol. Corneas were stained with Rose Bengal (RB, 0.1%) for 2 minutes and then exposed to green light (532 nm) at 0.25 W/cm2 for times to deliver doses of 50, 100, 150, or 200 J/cm2 (n = 5 per group). Five corneas were pretreated with riboflavin solution (0.1% riboflavin) for 15 minutes and irradiated with ultraviolet A (UVA) light (370 nm, 3 mW/cm2) for 30 minutes. Five corneas underwent only de-epithelialization and were otherwise untreated. Five corneas were stained with RB without light exposure. The central corneas of each group was removed with a 8.5-mm trephine and incubated at 37°C in 0.3% collagenase A solution. Time to dissolution of each cornea was compared across treatments.

Results: Corneas treated with RGX were treated with light fluences of 50, 100, 150, and 200 J/cm2; these corneas dissolved completely at 8.3 ± 1.2, 11.1 ± 1.4, 12.4 ± 1.7, and 15.7 ± 1.8 hours, respectively. Corneas treated by riboflavin and UVA light dissolved at 15.7 ± 1.7 hours, and nontreated corneas dissolved at 6.1 ± 1.3 hours. Corneas treated with only RB (no green light) dissolved at 9.3 ± 1.7 hours. Compared with the untreated corneas, all of the RB groups and the riboflavin-UVA-treated group of corneas degraded statistically significantly slower than untreated corneas (P < 0.05).

Conclusions: Crosslinking with RGX increased corneal resistance to digestion by collagenase comparable to that produced by riboflavin and UVA treatment.
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http://dx.doi.org/10.1167/iovs.15-18764DOI Listing
December 2016

Novel Phagocytosis-Resistant Extended-Spectrum β-Lactamase-Producing Escherichia coli From Keratitis.

JAMA Ophthalmol 2016 Nov;134(11):1306-1309

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts2Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts.

Importance: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are highly antibiotic resistant, and primary ocular infection by ESBL E coli has rarely been reported. A novel mutation conferring phagocytosis resistance would position a strain well to infect the cornea.

Observations: A woman with recurrent keratitis presented with a corneal ulcer, which was culture positive for ESBL E coli. Resistant to nearly all other antimicrobials, the infection was treated with amikacin and polymyxin B-trimethoprim, and the ulcer resolved over 3 weeks. Analysis of the E coli genome showed it to belong to multilocus sequence type 131 (ST131). This isolate was found to possess a novel deletion in yrfF, an essential regulator of bacterial capsule synthesis. Disruption of yrfF, which confers mucoidy and increased virulence, has not been previously observed in ESBL E coli from any infection site. This novel variant was experimentally proven to cause the mucoid phenotype, and corresponding resistance to phagocytic killing.

Conclusions And Relevance: Increased resistance to immune clearance in an ESBL E coli lineage already known for its virulence is an unsettling development. This phenotype, which likely positioned it as an unusual cause of corneal ulcer, can be easily recognized in the laboratory, which should help limit its spread.
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http://dx.doi.org/10.1001/jamaophthalmol.2016.3283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106311PMC
November 2016

Latanoprost-Eluting Contact Lenses in Glaucomatous Monkeys.

Ophthalmology 2016 10 29;123(10):2085-92. Epub 2016 Aug 29.

Departments of Anesthesia and Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Purpose: To assess the ability of latanoprost-eluting contact lenses to lower the intraocular pressure (IOP) of glaucomatous eyes of cynomolgus monkeys.

Design: Preclinical efficacy study of 3 treatment arms in a crossover design.

Participants: Female cynomolgus monkeys with glaucoma induced in 1 eye by repeated argon laser trabeculoplasty.

Methods: Latanoprost-eluting low-dose contact lenses (CLLO) and high-dose contact lenses (CLHI) were produced by encapsulating a thin latanoprost-polymer film within the periphery of a methafilcon hydrogel, which was lathed into a contact lens. We assessed the IOP-lowering effect of CLLO, CLHI, or daily latanoprost ophthalmic solution in the same monkeys. Each monkey consecutively received 1 week of continuous-wear CLLO, 3 weeks without treatment, 5 days of latanoprost drops, 3 weeks without treatment, and 1 week of continuous-wear CLHI. On 2 consecutive days before initiation of each study arm, the IOP was measured hourly over 7 consecutive hours to establish the baseline IOP. Two-tailed Student t tests and repeated-measures analysis of variance were used for statistical analysis.

Main Outcome Measures: Intraocular pressure.

Results: Latanoprost ophthalmic solution resulted in IOP reduction of 5.4±1.0 mmHg on day 3 and peak IOP reduction of 6.6±1.3 mmHg on day 5. The CLLO reduced IOP by 6.3±1.0, 6.7±0.3, and 6.7±0.3 mmHg on days 3, 5, and 8, respectively. The CLHI lowered IOP by 10.5±1.4, 11.1±4.0, and 10.0±2.5 mmHg on days 3, 5, and 8, respectively. For the CLLO and CLHI, the IOP was statistically significantly reduced compared with the untreated baseline at most time points measured. The CLHI demonstrated greater IOP reduction than latanoprost ophthalmic solution on day 3 (P = 0.001) and day 5 (P = 0.015), and at several time points on day 8 (P < 0.05).

Conclusions: Sustained delivery of latanoprost by contact lenses is at least as effective as delivery with daily latanoprost ophthalmic solution. More research is needed to determine the optimal continuous-release dose that would be well tolerated and maximally effective. Contact lens drug delivery may become an option for the treatment of glaucoma and a platform for ocular drug delivery.
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http://dx.doi.org/10.1016/j.ophtha.2016.06.038DOI Listing
October 2016

A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease.

Ophthalmology 2016 07 13;123(7):1449-57. Epub 2016 Apr 13.

Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. Electronic address:

Purpose: To evaluate the safety and efficacy of topical tacrolimus 0.05% versus topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD).

Design: Phase 1/2 prospective, randomized, double-masked clinical trial.

Participants: Eighty eyes of 40 patients diagnosed with chronic ocular GVHD were enrolled.

Methods: Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients were treated with topical methylprednisolone 0.5% twice daily for 10 weeks, in addition to continuing their baseline treatment regimen.

Main Outcome Measures: Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subject reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy end points were corneal fluorescein staining (CFS), tear film break-up time (TBUT), Schirmer test results, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI).

Results: After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the 2 groups (P = 0.06). However, burning sensation was more pronounced with tacrolimus (P = 0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P = 0.01) and achieved significant improvement in TBUT when compared with baseline (P < 0.001). Reduction in OSDI score achieved statistical significance with tacrolimus (27% reduction; P = 0.02), but was marginal with methylprednisolone (32% reduction; P = 0.06). Expression of ICAM-1 by ocular surface epithelium decreased significantly in both groups (tacrolimus, P = 0.003; methylprednisolone, P = 0.008), whereas HLA-DR expression decreased significantly only in the tacrolimus group (P = 0.03). Schirmer test scores did not change significantly in either group during the study; IOP increased significantly with methylprednisolone at week 10 (P = 0.04).

Conclusions: Topical tacrolimus 0.05% is safe, generally well tolerated, and effective for the treatment of ocular GVHD without the hypertensive effects of topical corticosteroids.
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http://dx.doi.org/10.1016/j.ophtha.2016.02.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921308PMC
July 2016

Revolutionary Future Uses of Contact Lenses.

Optom Vis Sci 2016 Apr;93(4):325-7

Waterloo, Canada Glassboro, NJ Boston, MA Jupiter, FL Sydney, Australia Sydney, Australia Waterloo, Canada.

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http://dx.doi.org/10.1097/OPX.0000000000000847DOI Listing
April 2016