C H Dohlman

Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States

Are you C H Dohlman?

Claim your profile

Publications (183)404.27 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to revisit the clinical paradigm attributed to Boston keratoprosthesis recipients presenting with idiopathic vitreous inflammation. A retrospective chart review was performed of keratoprosthesis recipients at Massachusetts Eye and Ear Infirmary, from January 2000 to August 2013, for demographic data, indication(s) for surgery, timing and presentation of vitreous inflammation, and best-corrected visual acuity at baseline, on presentation, and after resolution of vitritis. Twenty-three (23 eyes) of 346 patients developed idiopathic vitreous inflammation after keratoprosthesis implantation. Six of 23 patients presented with signs and symptoms similar to infectious endophthalmitis but were culture negative. The proportion of patients who fit the previous paradigm of sudden painless loss of vision without external signs of infection ("sterile vitritis") at their first presentation with vitritis was only 4 of 23. Vision decline was variable (median, 9 lines on Snellen chart; range, 0-24), as was time to recovery of best vision (median, 8.9 weeks; range, 0.9-36.7). Nine eyes had repeat bouts (43 episodes in 23 patients). Ten of 43 episodes did not recover to baseline vision. Seventeen of 23 eyes with idiopathic vitritis after keratoprosthesis later developed other complications. The current paradigm for idiopathic vitritis after keratoprosthesis implantation includes sudden painless loss of vision with full recovery of vision on treatment with periocular corticosteroids. However, idiopathic vitritis after keratoprosthesis can also mimic infectious endophthalmitis with pain and external signs of inflammation. Visual loss can be gradual. Vision may not recover to baseline despite treatment. Vitritis may be a part of a common pathway of chronic inflammation after keratoprosthesis.
    Cornea 12/2014; · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Purpose To compare corneal inflammation after syngeneic and allogeneic penetrating keratoplasty (PK) with miniature Keratoprosthesis (m-KPro) implantation in mice. Methods BALB/C (syngeneic) or C57BL/6 (allogeneic) corneas were transplanted onto BALB/C host beds as part of PK or m-KPro implantation. Corneal inflammation was assessed by determining the frequencies of CD45+ leukocytes, CD4+ T cells, CD11b+ cells, and Gr-1+ granulocytes/monocytes by flow cytometry at 2, 4, and 8 weeks post-transplantation. In addition, expression levels of the pro-inflammatory cytokines Tumor necrosis factor alpha (TNFα) and interleukin 1 beta (IL-1β) were analyzed using Real-Time qPCR at 8 weeks post-transplantation. Results Cell frequencies in the syngeneic (syn) and allogeneic (allo) m-KPro groups were higher compared with the syngeneic and allogeneic PK groups, respectively, at all time points. However, after week four, frequencies of all analyzed immune cells were higher in the alloPK group as compared with synKPro group. At eight weeks, the expression of TNFα was higher in synKPro, alloPK, and alloKPro groups compared to the naïve and synPK groups. The expression of IL-1β was significantly higher in both KPro groups as compared to PK groups. Conclusion Although the m-KPro device augments the inflammatory response in the cornea after its implantation, allogenicity (of the carrier tissue) is also a significant contributor to corneal inflammation. These data suggest that using syngeneic or decellularized corneal tissue as a Boston-KPro carrier could reduce the post-operative inflammation response. Copyright © 2014 by Association for Research in Vision and Ophthalmology.
    Investigative Ophthalmology &amp Visual Science 12/2014; · 3.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To measure the through-focus curve for eyes implanted with a type 1 Boston keratoprosthesis (KPro) and compare it to that of pseudophakic controls with fixed pupil sizes. The results should assist in evaluating postoperative visual quality after surgery. They should also help to determine the necessary KPro inventories in terms of refractive power steps. Autorefraction and manifest refraction were performed on all eyes. The monocular through-focus acuity curve was plotted in reference to the best-corrected visual acuity by spectacle plane defocus ranging from +5.00 to -5.00 dioptres in 0.50 dioptre increments. These measurements were obtained on KPro-implanted eyes, pseudophakic eyes as controls, and on the same control eyes after fixing the pupil diameter to 3 and 2 mm using black painted iris contact lenses. Ten KPro eyes and five control eyes were included. Good agreement was noted between the subjective refractions and autorefraction in KPro eyes. The average through-focus curve for the control eyes was significantly steeper than that of the KPro curve, but became comparable after fixing the control pupil to 2 and 3 mm. The KPro's wide depth-of-focus makes the visual acuity less dependent on an exact refractive correction at distance and explains the 'pseudoaccomodation' experienced by these patients. This is primarily due to the small pupil diameter of the KPro. The current manufacturing steps in 0.50 dioptre increments appears to be sufficient. © 2014 The Authors Ophthalmic & Physiological Optics © 2014 The College of Optometrists.
    Ophthalmic and Physiological Optics 11/2014; · 1.74 Impact Factor
  • Marie-Claude Robert, Claes H Dohlman
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Use of the Boston Keratoprosthesis (B-KPro) has grown significantly, both in the United States and overseas over the course of the last decade. It is the most frequently employed keratoprosthesis for the management of complex corneal blindness. Improving outcomes and reductions in devastating complications such as corneal melting and infection have motivated this increase in use. We review the epidemiology and pathophysiology of corneal melting following B-KPro as well as the advances in B-KPro design and postoperative care that have halted the occurrence of melting. Eyes with autoimmune diseases such as Stevens-Johnson syndrome, toxic epidermal necrolysis syndrome, and mucous membrane pemphigoid remain particularly vulnerable to corneal melt, leak, and extrusion. The development of new strategies to prevent melting in eyes with autoimmune disease is crucial to improve the outcomes of this group of patients, as they are often those with the most desperate need for visual rehabilitation with a B-KPro.
    Seminars in Ophthalmology 11/2014; 29(5-6):349-57. · 1.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to develop a novel 10-mg/mL infliximab eye drop, to characterize its physical and biological stability under recommended storage conditions, and to assess the formulation's toxicity to ocular surface epithelium in vitro. Infliximab (10 mg/mL) was reconstituted using equal volumes of sterile water and 1% carboxymethylcellulose artificial tears. Aliquots were stored in either a 4 degrees C refrigerator or -20 degrees C freezer for up to 45 days. Physical stability was assessed through monitoring the solution's appearance, pH, ultraviolet-visible-near infrared absorbance and scattering, as well as protein gel electrophoresis. Biological stability was assayed through binding to tumor necrosis factor-alpha using an enzyme-linked immunosorbent assay. In vitro cytotoxicity to human corneal-limbal epithelial cells was examined following a 4-hour exposure to the study drug. Refrigerated and frozen infliximab eye drops remained clear and colorless for the duration of study. The formulation's pH (7.0) was comparable to that of the artificial tear vehicle alone. Low levels of ultraviolet-visible-near infrared light absorbance and scattering established the lack of protein precipitate after refrigeration or freezing. Protein gel electrophoresis performed under reducing conditions revealed the presence of two main protein bands of approximately 50 kDa and 25 kDa, representing immunoglobulin G heavy and light chains. The migration pattern of the proteins did not change under the different storage conditions and between day 10 and 45 after formulation. Infliximab binding to tumor necrosis factor-alpha remained stable for up to 45 days, with conservation of 101% and 102% of its initial binding activity when refrigerated or frozen, respectively. In vitro human corneal-limbal epithelial cultures showed no increase in cytotoxicity with infliximab treatment when compared to vehicle and culture media controls (P > 0.05). Infliximab can be formulated as an eye drop and remains stable when stored in accordance with current regulations regarding compounded eye drops. The demonstrated physical and biological stability as well as in vitro innocuity of this infliximab eye drop formulation may facilitate future clinical investigation targeting tumor necrosis factor-alpha as a modulator of various ocular surface diseases.
    International Journal of Pharmaceutical Compounding 09/2014; 18(5):418-26.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to develop a modified ex vivo corneal cross-linking method that increases stromal resistance to enzymatic degradation for use as a carrier for the Boston keratoprosthesis.
    Cornea 07/2014; · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose:To establish a murine model for keratoprosthesis. Methods: A miniature keratoprosthesis (m-KPro) device was created consisting of a poly[methyl methacrylate] front part and a titanium back plate, designed after the Boston KPro, which is in widespread clinical use. BALB/c mice were used and a 2 mm in diameter donor cornea was punched out. After 2 mm trepanation of the syngeneic recipient cornea, extra-capsular crystalline lens extraction was performed. The m-KPro was assembled onto the cornea button in a similar manner to human KPro implantation. The cornea-device complex was secured to the recipient bed with eight interrupted 11-0 sutures. All mice (n=10) were followed for 8 weeks postoperatively. Results: All m-KPros were successfully implanted and retained in all 10 animals. There were no critical complications such as endophthalmitis, corneal melting, device extrusions, leakage, extensive inflammation, or weight loss in the animals. We observed mild to moderate donor and host corneal neovascularization in all cases throughout the follow-up period. Conclusions: We have established a novel murine model of KPro implantation, which mirrors clinical KPro with high fidelity. This model will allow for further studies of immune responses after KPro surgery.
    Investigative ophthalmology & visual science 05/2014; · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Boston Keratoprosthesis (KPro) is one of several types of artificial cornea manufactured worldwide that are being implanted in increasing numbers in patients with severe corneal diseases and graft failures. To summerize the advances in design of the Boston type I keratoprosthesis and in the treatment strategies to conquer the post operative complications have expanded the indications and application of this technology. Many modifications to the design of the Boston type I keratoprosthesis and treatment of the patient in the post operative period have occurred. Also, the technology has been more widely accepted as a primary surgical option for patients with a poor preoperative prognosis for traditional penetrating keratoplasty. The outcomes of visual acuity, retention, and post-operative infection rates have all significantly improved since the technology has been modified and offers patients an alternative for visual rehabilitation. This is implanted into a carrier corneal graft or into the patient's own cornea. The allograft cornea can be the carrier, which may solve the shortage of donor cornea in China.
    [Zhonghua yan ke za zhi] Chinese journal of ophthalmology 04/2014; 50(4):307-12.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to evaluate glaucoma onset and progression after implantation of Boston Keratoprostheses (B-KPro) and the role of glaucoma surgery. Records of patients with B-KPro implantation during 2004 to 2009 were reviewed. Parameters relevant to B-KPro surgery and glaucoma status were recorded. The data were analyzed in 5 groups based on the preoperative diagnosis. One hundred six eyes of 87 patients were included, and the average age was 54 ± 6.7 years. Forty-six percent were female. Eighteen eyes had a B-KPro with a titanium back plate, and the others had a poly(methyl methacrylate) back plate. Thirty-three eyes were pseudophakic, and the rest were left aphakic. The follow-up time was 3.3 ± 1.0 years. Indications for implantation included past infection, congenital glaucoma, trauma, autoimmune diseases, aniridia, burns, and others. Sixty-six percent of the eyes had glaucoma preoperatively, and 26% developed de novo glaucoma afterward. The mean intraocular pressure (by finger palpation) was 16.5 ± 5.7 mm Hg. Reliable visual field tests were only available in 59% of the eyes; hence, the cup-to-disc ratio of the optic nerve head was used as the main outcome measure. In B-KPro-implanted eyes with glaucoma, 65% had undergone glaucoma surgery at some point, and 30% did not show progression. Thirty-one percent of the total cohort had disc pallor with a cup-to-disc ratio of <0.8. Glaucoma in B-KPro remains a challenge, despite aggressive attempts to slow down its progression. Patients with glaucoma before B-KPro implantation should be considered for glaucoma surgery before or simultaneously with B-KPro implantation. The high number of eyes with disc pallor suggests that additional mechanisms other than elevated intraocular pressure may play a role in optic neuropathy.
    Cornea 02/2014; · 1.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to evaluate early retinal damage after induction of ocular surface alkali burns and the protective effects of tumor necrosis factor alpha (TNF-α) blockade. Alkali injury was induced in mouse corneas by using 1 N NaOH. Retinal damage was assessed using a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5-triphosphate nick end labeling (TUNEL) assay, 15 minutes to 14 days postburn. Immune cell infiltration was assessed by CD45 immunolocalization. Retinal cytokines were quantified using the enzyme-linked immunosorbent assay for interleukin (IL)1β, IL2, IL6, TNF-α, CCL5, and macrophage inflammatory protein-1α. Protection against retinal damage was attempted with a single dose of either anti-TNF-α antibody (infliximab, 6.25 mg/kg) or control immunoglobulin G (IgG), administered intraperitoneally 15 minutes after the burn was inflicted. Corneal injury was evaluated by using TUNEL and CD45 immunolocalization and by quantifying corneal neovascularization. There was significant damage to the retina within 24 hours of the corneal burn being inflicted. TUNEL+ labeling was present in 80% of the retinal ganglion cells, including a few CD45+ cells. There was a 10-fold increase in the retinal inflammatory cytokines in the study groups compared with that in controls. A single intraperitoneal dose of anti-TNF-α antibody, administered 15 minutes after the burn, markedly reduced retinal TUNEL+, CD45+ labeling, and inflammatory cytokine expression, compared with that in the controls. Additionally, TNF-α blockade caused a marked reduction in corneal neovascularization, and in cornea TUNEL and CD45 labeling, 5 days after the burn. This study shows that alkali corneal burns can induce significant retinal damage within 24 hours. A single dose of anti-TNF-α antibody, administered 15 minutes after inflicting the burn, provides significant retinal and corneal protection. This could lead to the discovery of novel therapies for patients with alkali injuries.
    Cornea 01/2014; · 1.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine the cumulative worldwide incidence of infectious endophthalmitis and associated vision loss after Boston keratoprosthesis (B-KPro) Type I/II implantation and to propose both safe and inexpensive prophylactic antibiotic regimens. Two retrospective methods were used to determine the incidence, visual outcomes and aetiologies of infectious endophthalmitis associated with the B-KPro divided per decade: (i) systematic review of the literature from 1990 through January 2013 and (ii) a surveillance survey sent to all surgeons who implanted B-KPros through 2010 with 1-year minimum follow-up. In addition, a single-Boston surgeon 20-year experience was examined. From 1990 through 2010, there were 4729 B-KPros implanted worldwide by 209 U.S. surgeons and 159 international surgeons. The endophthalmitis cumulative mean incidence declined from 12% during its first decade of use to about 3% during its second decade in the Unites States and about 5% internationally during the second decade. There remains a large incidence range both in the United States (1-12.5%) and internationally (up to 17%). Poor compliance with daily topical antibiotics is an important risk factor. While Gram-positive organisms remained dominant, fungal infections emerged during the second decade. Daily prophylactic topical antibiotics have dramatically reduced the endophthalmitis incidence. Although Gram-positive organisms are the most common aetiology, antimicrobials must be inclusive of Gram-negative organisms. Selection of prophylactic regimens should be tailored to local antibiotic susceptibility patterns, be cost-effective, and should not promote the emergence of antimicrobial resistance. An example of a broad-spectrum, low-cost prophylactic option for non-autoimmune patients includes trimethoprim/polymyxinB once daily.
    Acta ophthalmologica 01/2014; · 2.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To present an autonomous intraocular pressure (IOP) measurement technique using a wireless implantable transducer (WIT) and a motion sensor. The WIT optical aid was implanted within the ciliary sulcus of a normotensive rabbit eye after extracapsular clear lens extraction. An autonomous wireless data system (AWDS) comprising of a WIT and an external antenna aided by a motion sensor provided continuous IOP readings. The sensitivity of the technique was determined by the ability to detect IOP changes resulting from the administration of latanoprost 0.005% or dorzolamide 2%, while the reliability was determined by the agreement between baseline and vehicle (saline) IOP. On average, 12 diurnal and 205 nocturnal IOP measurements were performed with latanoprost, and 26 diurnal and 205 nocturnal measurements with dorzolamide. No difference was found between mean baseline IOP (13.08±2.2 mmHg) and mean vehicle IOP (13.27±2.1 mmHg) (P=0.45), suggesting good measurement reliability. Both antiglaucoma medications caused significant IOP reduction compared to baseline; latanoprost reduced mean IOP by 10% (1.3±3.54 mmHg; P<0.001), and dorzolamide by 5% (0.62±2.22 mmHg; P<0.001). Use of latanoprost resulted in an overall twofold higher IOP reduction compared to dorzolamide (P<0.001). Repeatability was ±1.8 mmHg, assessed by the variability of consecutive IOP measurements performed in a short period of time (≤1 minute), during which the IOP is not expected to change. IOP measurements in conscious rabbits obtained without the need for human interactions using the AWDS are feasible and provide reproducible results.
    Clinical ophthalmology (Auckland, N.Z.) 01/2014; 8:177-85.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to assess the possibility of light damage to the retina by a surgical microscope during implantation of a Boston Keratoprosthesis (B-KPro) in rabbits. The retinal irradiance from a Zeiss OPMI Lumera S7 operating microscope was measured at the working distance (16.5 cm). Light transmittance through an isolated B-KPro was measured. A B-KPro was implanted into 1 eye of 12 rabbits with the optic covered during the procedure. The operated eyes were then continuously exposed to a fixed light intensity under the microscope for 1 hour. Fluorescein angiography was carried out on days 2 and 9 postsurgery, after which the animals were euthanized. Further, we compared the potential of these retinal exposures to well-accepted light safety guidelines applicable to humans. Light transmittance of B-KPro revealed a blockage of short wavelengths (<390 nm) and of long wavelengths (1660-1750 nm) of light. In addition, the surgical microscope filtered a part of the blue, ultraviolet, and infrared wavelengths. Neither fluorescein angiography nor a histological examination showed any morphological retinal changes in our rabbits. Moreover, the retinal exposures were well below the safety limits. Modern surgical microscopes have filters incorporated in them that block the most damaging wavelengths of light. The B-KPro is made of 100% poly(methyl methacrylate), which makes it in itself a blocker of short wavelengths of light. No damage could be demonstrated in the animal study, and the retinal exposures were well below the safety limits. Together, these results suggest that light exposures during B-KPro surgery present a low risk of photochemical damage to the retina.
    Cornea 12/2013; · 1.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To compare the anatomy of the graft-host junction and anterior chamber angle after Boston Keratoprosthesis (KPro) placement using oversized (9.5-mm) and standard (8.5-mm) back plates. Six patients with 9.5-mm titanium back plates and 10 patients with 8.5-mm titanium back plates were imaged by anterior segment optical coherence tomography 6 to 12 months after KPro placement. The location of the graft-host junction in relation to the back plate, the corneal thickness at the graft-host junction, and the anterior chamber angle were assessed. The clinical outcomes and incidence of retroprosthetic membrane (RPM) formation in this cohort were retrospectively evaluated. The oversized back plates completely covered the graft-host junction in all quadrants, allowing the complete apposition of the posterior surface of the carrier graft with the host cornea, with decreased graft-host junction wound thickness. The standard back plates covered the posterior aspect of the carrier graft but not the graft-host junction or the host cornea, resulting in a significantly thicker graft-host junction. None of the patients with larger back plates developed a significant RPM during a 12-month follow-up period. One patient with a larger back plate developed a corneal melt at the KPro stem as a result of chronic exposure. Oversized KPro back plates effectively cover the graft-host junction without any adverse effects on angle anatomy or wound healing. This may be a strategy to provide better wound apposition, reduce RPM formation, and reduce angle closure from iris synechiae to the wound.
    Cornea 10/2013; · 1.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To investigate the levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in tears of patients with Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP). Design: Prospective, noninterventional cohort study. Participants: Four SJS patients (7 eyes), 19 OCP patients (37 eyes), and 20 healthy controls who underwent phacoemulsification (40 eyes). Methods: Tear washes were collected from all patients and were analyzed for levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 using multianalyte bead-based enzyme-linked immuno-sorbent assays. Total MMP activity was determined using a fluorometric assay. Correlation studies were per-formed between the various analytes within study groups. Main Outcome Measures: Levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 (in nanograms per microgram of protein) and total MMP activity (in relative fluorescent units per minute per microgram of protein) in tears; MMP-8etoeTIMP-1 ratio; MMP-9etoeTIMP-1 ratio; and the correlations between MMP-8 and MMP-9 and both MMP and MPO. Results: MMP-8, MMP-9, and MPO levels were elevated significantly in SJS and OCP tears (SJS>OCP) when compared with controls. The MMP activity was highest in SJS patients, whereas OCP patients and controls showed lower and similar activities. The TIMP-1 levels were decreased in SJS and OCP patients when compared with those in controls, with levels in OCP patients reaching significance. The MMP-8etoeTIMP-1 and MMP-9etoeTIMP-1 ratios were markedly elevated in SJS and OCP tears (SJS>OCP) when compared with those of controls. Across all study groups, MMP-9 levels correlated strongly with MMP-8 and MPO levels, and MMP-8 correlated with MPO, but it did not reach significance in SJS patients. There was no relationship between MMP-7 and MPO. Conclusions: Because MMP-8 and MPO are produced by inflammatory cells, particularly neutrophils, the correlation data indicate that they may be the common source of elevated enzymes, including MMP-9, in SJS and OCP tears. Elevated MMP-to-TIMP ratios and MMP activity suggest an imbalance in tear MMP regulation that may explain the predisposition of these patients to demonstrate corneal melting and chronic complications associated with persistent inflammation. Myeloperoxidase in tears may be a sensitive and specific marker for the quantification of ocular inflammation. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2013;-:1e9 ª 2013 by the American Academy of Ophthalmology. Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP), a subset of mucous membrane pem-phigoid, are rare, yet severe, systemic autoimmune diseases associated with extensive bilateral persistent inflammation of the ocular surface and lid margins. Although the term mucous membrane pemphigoid has been widely accepted to describe this disease, in this manuscript, ocular cicatricial pemphigoid has been used instead to minimize confusion between the acronym of mucous membrane pemphigoid and that universally used for matrix metalloproteinases (MMPs) assayed in this study. 1e4 If left untreated or inadequately
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To investigate the levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in tears of patients with Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP). Design: Prospective, noninterventional cohort study. Participants: Four SJS patients (7 eyes), 19 OCP patients (37 eyes), and 20 healthy controls who underwent phacoemulsification (40 eyes). Methods: Tear washes were collected from all patients and were analyzed for levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 using multianalyte bead-based enzyme-linked immuno-sorbent assays. Total MMP activity was determined using a fluorometric assay. Correlation studies were per-formed between the various analytes within study groups. Main Outcome Measures: Levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 (in nanograms per microgram of protein) and total MMP activity (in relative fluorescent units per minute per microgram of protein) in tears; MMP-8etoeTIMP-1 ratio; MMP-9etoeTIMP-1 ratio; and the correlations between MMP-8 and MMP-9 and both MMP and MPO. Results: MMP-8, MMP-9, and MPO levels were elevated significantly in SJS and OCP tears (SJS>OCP) when compared with controls. The MMP activity was highest in SJS patients, whereas OCP patients and controls showed lower and similar activities. The TIMP-1 levels were decreased in SJS and OCP patients when compared with those in controls, with levels in OCP patients reaching significance. The MMP-8etoeTIMP-1 and MMP-9etoeTIMP-1 ratios were markedly elevated in SJS and OCP tears (SJS>OCP) when compared with those of controls. Across all study groups, MMP-9 levels correlated strongly with MMP-8 and MPO levels, and MMP-8 correlated with MPO, but it did not reach significance in SJS patients. There was no relationship between MMP-7 and MPO. Conclusions: Because MMP-8 and MPO are produced by inflammatory cells, particularly neutrophils, the correlation data indicate that they may be the common source of elevated enzymes, including MMP-9, in SJS and OCP tears. Elevated MMP-to-TIMP ratios and MMP activity suggest an imbalance in tear MMP regulation that may explain the predisposition of these patients to demonstrate corneal melting and chronic complications associated with persistent inflammation. Myeloperoxidase in tears may be a sensitive and specific marker for the quantification of ocular inflammation. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2013;-:1e9 ª 2013 by the American Academy of Ophthalmology. Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP), a subset of mucous membrane pem-phigoid, are rare, yet severe, systemic autoimmune diseases associated with extensive bilateral persistent inflammation of the ocular surface and lid margins. Although the term mucous membrane pemphigoid has been widely accepted to describe this disease, in this manuscript, ocular cicatricial pemphigoid has been used instead to minimize confusion between the acronym of mucous membrane pemphigoid and that universally used for matrix metalloproteinases (MMPs) assayed in this study. 1e4 If left untreated or inadequately
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in tears of patients with Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP). Prospective, noninterventional cohort study. Four SJS patients (7 eyes), 19 OCP patients (37 eyes), and 20 healthy controls who underwent phacoemulsification (40 eyes). Tear washes were collected from all patients and were analyzed for levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 using multianalyte bead-based enzyme-linked immunosorbent assays. Total MMP activity was determined using a fluorometric assay. Correlation studies were performed between the various analytes within study groups. Levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 (in nanograms per microgram of protein) and total MMP activity (in relative fluorescent units per minute per microgram of protein) in tears; MMP-8-to-TIMP-1 ratio; MMP-9-to-TIMP-1 ratio; and the correlations between MMP-8 and MMP-9 and both MMP and MPO. MMP-8, MMP-9, and MPO levels were elevated significantly in SJS and OCP tears (SJS>OCP) when compared with controls. The MMP activity was highest in SJS patients, whereas OCP patients and controls showed lower and similar activities. The TIMP-1 levels were decreased in SJS and OCP patients when compared with those in controls, with levels in OCP patients reaching significance. The MMP-8-to-TIMP-1 and MMP-9-to-TIMP-1 ratios were markedly elevated in SJS and OCP tears (SJS>OCP) when compared with those of controls. Across all study groups, MMP-9 levels correlated strongly with MMP-8 and MPO levels, and MMP-8 correlated with MPO, but it did not reach significance in SJS patients. There was no relationship between MMP-7 and MPO. Because MMP-8 and MPO are produced by inflammatory cells, particularly neutrophils, the correlation data indicate that they may be the common source of elevated enzymes, including MMP-9, in SJS and OCP tears. Elevated MMP-to-TIMP ratios and MMP activity suggest an imbalance in tear MMP regulation that may explain the predisposition of these patients to demonstrate corneal melting and chronic complications associated with persistent inflammation. Myeloperoxidase in tears may be a sensitive and specific marker for the quantification of ocular inflammation. The author(s) have no proprietary or commercial interest in any materials discussed in this article.
    Ophthalmology 08/2013; · 5.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To present a novel design of an implantable glaucoma valve based on ferrofluidic nanoparticles and to compare it with a well-established FDA approved valve. Massachusetts Eye & Ear Infirmary, Boston, USA. A glaucoma valve was designed using soft lithography techniques utilizing a water-immiscible magnetic fluid (ferrofluid) as a pressure-sensitive barrier to aqueous flow. Two rare earth micro magnets were used to calibrate the opening and closing pressure. In-vitro flow measurements were performed to characterize the valve and to compare it to Ahmed™ glaucoma valve. The reliability and predictability of the new valve was verified by pressure/flow measurements over a period of three months and X-ray diffraction (XRD) analysis over a period of eight weeks. In vivo assessment was performed in three rabbits. In the in vitro experiments, the opening and closing pressures of the valve were 10 and 7 mmHg, respectively. The measured flow/pressure response was linearly proportional and reproducible over a period of three months (1.8 µl/min at 12 mmHg; 4.3 µl/min at 16 mmHg; 7.6 µl/min at 21 mmHg). X-ray diffraction analysis did not show oxidization of the ferrofluid when exposed to water or air. Preliminary in vivo results suggest that the valve is biocompatible and can control the intraocular pressure in rabbits. The proposed valve utilizes ferrofluid as passive, tunable constriction element to provide highly predictable opening and closing pressures while maintaining ocular tone. The ferrofluid maintained its magnetic properties in the aqueous environment and provided linear flow to pressure response. Our in-vitro tests showed reliable and reproducible results over a study period of three months. Preliminary in-vivo results were very promising and currently more thorough investigation of this device is underway.
    PLoS ONE 06/2013; 8(6):e67404. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: Recent use of a titanium (Ti) backplate has improved the design and biocompatibility of the Boston Keratoprosthesis (BKpro). Titanium's shiny metallic appearance, however, makes the cosmetic outcome less favorable. The purpose of this study was to develop and test a coloring surface modification of Ti. METHOD: Ti coloring was achieved using electrochemical anodization. Color assessment included: scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray diffraction crystallography (XRD), and Fourier transform infrared spectroscopy (FTIR). Biocompatibility assessment of Ti disks included: in vitro proliferation and cytotoxicity in co-culture with human corneal limbal epithelial cells (HCLE), primary human corneal fibroblasts and immortalized human corneal endothelial cells (HCEnCs) and in vivo intralamellar implantation in rabbit corneas. Histologic appearance (H&E and trichrome staining) and presence of cell inflammation (CD45), apoptosis (TUNEL) and corneal neovascularization (CD31) was evaluated 27 and 53 days post implantation. RESULTS: Blue and brown coloration of Ti was achieved. Analysis showed the presence of a nanoporous oxide surface with no chemical change of the modified Ti surface. In vitro assessment showed no significant differences in cell proliferation and cytotoxicity between anodized and non-anodized Ti (p> 0.05; ANOVA for all cell types). Analysis of corneal tissues harboring the Ti disks showed normal cellular appearance, and lack of CD45, TUNEL and CD31 positive cells. CONCLUSION: A biocompatible Ti backplate coloring was achieved by electrochemical anodization. In vitro and in vivo results suggest that the anodized Ti is equally biocompatible and as safe as the standard non-anodized Ti. The color modification of the BKpro may improve the cosmesis and acceptance of the BKpro by patients.
    Investigative ophthalmology & visual science 05/2013; · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE:: To evaluate the use of the Boston keratoprosthesis type I implantation in patients with mucous membrane pemphigoid (MMP). METHODS:: Retrospective review of 8 eyes of 8 patients with severe ocular surface disease and corneal blindness as a result of MMP who underwent Boston keratoprosthesis type I implantation at the Massachusetts Eye and Ear Infirmary from January 1, 2000, through December 31, 2009. The main outcome measures were best-corrected visual acuity, keratoprosthesis retention, and postoperative complications. RESULTS:: The mean age of patients was 71.3 years (range, 55-94 years), and the mean duration of their disease preoperatively was 6.1 years (range, 1.7-11.4 years). Visual acuity after the surgery improved to 20/200 or better in 6 eyes (75%) and to 20/40 or better in 3 eyes (37.5%). Only 1 of 6 eyes (16.7%) was able to maintain visual acuity of 20/200 or better over a mean follow-up period of 3.2 years. Five of the 8 Boston keratoprosthesis type I devices (62.5%) extruded or had to be replaced during a mean follow-up time of 1.7 ± 1.7 years. Loss of vision to worse than 20/200 during the follow-up period occurred because of keratoprosthesis type I extrusion, end-stage glaucoma, and retinal or choroidal detachment. CONCLUSIONS:: The clinical outcomes of Boston keratoprosthesis type I implantation in MMP are guarded and, as judged from the literature, less favorable than those with the Boston keratoprosthesis type II for the same disease.
    Cornea 03/2013; · 1.75 Impact Factor

Publication Stats

3k Citations
404.27 Total Impact Points

Institutions

  • 1970–2014
    • Massachusetts Eye and Ear Infirmary
      • • Department of Ophthalmology
      • • Cornea Service
      Boston, Massachusetts, United States
  • 2013
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 1998–2013
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2012
    • Boston Children's Hospital
      • Department of Ophthalmology
      Boston, MA, United States
  • 2011
    • Universidade Federal de São Paulo
      San Paulo, São Paulo, Brazil
  • 2009
    • Massachusetts General Hospital
      • Division of Infectious Diseases
      Boston, MA, United States
  • 2008
    • Université de Montréal
      • Department of Ophthalmology
      Montréal, Quebec, Canada
  • 2007
    • Johns Hopkins Medicine
      • Wilmer Eye Institute
      Baltimore, MD, United States
  • 2003
    • University of Texas Medical Branch at Galveston
      Galveston, Texas, United States
  • 1976
    • Boston Biomedical Research Institute
      Boston, Massachusetts, United States