David M Meisler

Medical College of Wisconsin, Milwaukee, WI, USA

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Publications (24)68.98 Total impact

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    Article: Management of focal limbal stem cell deficiency associated with soft contact lens wear.
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    ABSTRACT: To present the varying manifestations of and the treatment methods for corneal epitheliopathies because of focal limbal stem cell deficiency (LSCD) associated with soft contact lens (SCL) wear. The medical records of patients seen at 3 institutions who developed focal LSCD, based on clinical examination, that was attributed to SCL wear were reviewed. Information regarding the patients' demographics, contact lens wearing schedules, medical and surgical treatment modalities, and clinical and visual outcomes were recorded. Eighteen eyes of 10 SCL wearers were found to have varying degrees of corneal epitheliopathy secondary to focal LSCD. Nine of the 10 patients (90%) were women, and the mean age of all patients was 35.1 years (range, 20-58 years). The mean duration of SCL wear was 15.2 years (range, 4-30 years). Two patients wore the lenses for 20 hours per day. Mean follow-up time was 7.0 months (range, 0.25-24 months). Visual acuity at first examination was affected in 10 of the 18 eyes (55.6%) and ranged from 20/30 to hand motions. The focal LSCD was found superiorly in all involved eyes and inferiorly in only 5 of 18 eyes (27.8%). The epitheliopathy resolved or stabilized in 11 eyes (61.1%) with cessation of SCL wear and use of artificial tears. Five eyes required topical corticosteroid eyedrops, and 2 eyes required surgical intervention. One eye had a best spectacle-corrected visual acuity of less than 20/30 at last follow-up. Focal LSCD can be a result of SCL wear, presenting with varying manifestations. SCL wearers should be monitored routinely and counseled on this possible complication. Early identification of focal LSCD in SCL wearers with subsequent cessation of wear may prevent the need for surgical intervention.
    Cornea 01/2011; 30(1):18-23. · 1.73 Impact Factor
  • Article: Clinical experience with Acanthamoeba keratitis at the cole eye institute, 1999-2008.
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    ABSTRACT: To review the clinical presentations, risk factors, medical and surgical management, and outcomes of patients with Acanthamoeba keratitis (AK). Retrospective review of laboratory and medical records of all patients suspected of having AK from January 1999 through May 2008 at Cole Eye Institute. Twenty-nine eyes of 26 patients were identified as having either culture- or tissue-proven AK or presumed AK based on clinical examination and complete response to full course of treatment. The most common risk factors identified for AK were history of contact lens wear (89.7%) and exposure to contaminated water (27.6%). Clinical presentations included early AK (superficial disease) in 37.9% of eyes or late AK (deep stromal disease with or without epithelial disease) in 62.1% of eyes. All early AK cases had best-corrected visual acuity of 20/30 or better at last follow-up, whereas only 55.6% of late AK cases achieved 20/30 or better. Eight eyes underwent penetrating keratoplasty. One patient demonstrated viable-appearing cysts in the corneal button, despite 15 months of maximum medical treatment and 5 months off all medical treatments. Over the nearly 10-year period, there was no significant increase in the number of cases seen each year. The most common risk factor for AK continues to be contact lens wear. AK requires prolonged and intense treatment, although good final visual acuity can be achieved. Potentially viable Acanthamoeba cysts can still persist in a noninflamed cornea after extensive medical therapy, supporting the practice that corneal transplantation after presumably resolved cases of AK should be followed with vigilance to detect the earliest signs of recurrent disease.
    Cornea 09/2010; 29(9):1016-21. · 1.73 Impact Factor
  • Article: Epithelial debridement for the treatment of epithelial basement membrane abnormalities coincident with endothelial disorders.
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    ABSTRACT: To determine if treatment directed at the epithelial basement membrane abnormalities in eyes with endothelial disorder can improve visual acuity and surface irregularity. Retrospective interventional case series of 4 eyes of 3 patients with epithelial basement membrane abnormalities and endothelial disorder coincident with Fuchs endothelial corneal dystrophy or iridocorneal endothelial syndrome that had initial treatment directed only at the epithelial basement membrane disorder. In 2 of the 4 eyes undergoing epithelial basement membrane debridement, visual acuity improved by 3 Snellen lines. In the other 2 eyes, the intervention improved visual acuity by 2 lines in 1 eye and no lines in the other, but the procedure allowed for accurate keratometry readings to be obtained for intraocular lens calculations before cataract surgery. Epithelial basement membrane abnormalities can occur in eyes with endothelial disorder. Treatment of the epithelial basement membrane disorder in these eyes can sometimes improve the regularity of the ocular surface and visual acuity.
    Cornea 01/2009; 27(10):1207-11. · 1.73 Impact Factor
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    Article: Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates.
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    ABSTRACT: Ocular Tracking Resistance in U.S. Today (TRUST) annually evaluates in vitro antimicrobial susceptibility of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim, and polymyxin B in national samples of ocular isolates. Laboratory investigation. Prospectively collected ocular isolates (197 S. aureus, 49 S. pneumoniae, and 32 H. influenzae) from 35 institutions and archived ocular isolates (760 S. pneumoniae and 356 H. influenzae) from 34 institutions were tested by an independent, central laboratory. Mean minimum inhibitory concentrations that would inhibit growth of 90% of the tested isolates (MIC(90)) were interpreted as susceptible, intermediate, or resistant according to standardized breakpoints for systemic treatment. S. aureus isolates were classified as methicillin susceptible (MSSA) or methicillin resistant (MRSA). MSSA or MRSA susceptibility patterns were virtually identical for the fluoroquinolones, that is, MSSA susceptibility was 79.9% to 81.1% and MRSA susceptibility was 15.2%. Trimethoprim was the only agent tested with high activity against MRSA. All S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; 89.8% were susceptible to ciprofloxacin. H. influenzae isolates were 100% susceptible to all tested agents but trimethoprim. Ocular TRUST 1 data were consistent with the eight-year longitudinal sample of archived ocular isolates. The fluoroquinolones were consistently active in MSSA, S. pneumoniae, and H. influenzae. After more than a decade of intensive ciprofloxacin and levofloxacin use as systemic therapy, 100% of ocular S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; nonsusceptibility to ciprofloxacin was less than 15%. High-level in vitro MRSA resistance suggests the need to consider alternative therapy to fluoroquinolones when MRSA is a likely pathogen.
    American Journal of Ophthalmology 07/2008; 145(6):951-958. · 4.22 Impact Factor
  • Article: Amantadine-associated corneal edema potentially irreversible even after cessation of the medication.
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    ABSTRACT: To describe the clinical features of 3 patients with amantadine-associated corneal edema, including the histopathologic findings from 1 patient who underwent corneal transplantation for irreversible corneal edema. Interventional case series. Three patients who sought treatment at the authors' institution with abrupt-onset, bilateral, diffuse corneal edema associated with systemic amantadine use. Retrospective chart review. Visual acuity, corneal thickness, slit-lamp observations, and histopathologic findings. The duration of use of amantadine ranged from 2 months to 6 years before onset of corneal edema. Discontinuation of amantadine resulted in resolution of corneal edema in both eyes of 2 patients. A third patient underwent a full-thickness corneal transplantation, and subsequently, edema developed in the grafted cornea. Cessation of amantadine therapy in this patient resulted in resolution of corneal edema in both eyes, but the ungrafted corneal eventually decompensated and became edematous, requiring corneal transplantation. Histopathologic analysis of the cornea buttons showed significant loss of endothelial cells. Amantadine can cause corneal edema that begins a few months to several years after institution of therapy, and the edema can occur even in a corneal graft. Prolonged corneal edema in the setting of amantadine use can be irreversible. In cases of corneal edema without an obvious causative disease, the systemic medication list of the patient must be reviewed, and amantadine must be considered as a possible cause.
    Ophthalmology 06/2008; 115(9):1540-4. · 5.45 Impact Factor
  • Article: Multivariate model of refractive shift in Descemet-stripping automated endothelial keratoplasty.
    William J Dupps, Ying Qian, David M Meisler
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    ABSTRACT: To relate in situ graft shape in Descemet-stripping automated endothelial keratoplasty (DSAEK) to surgically induced refractive error. Academic eye institute. High frequency arc-scanning ultrasound was performed in 7 patients enrolled in a prospective study of microkeratome-assisted endothelial keratoplasty approved by the Investigative Review Board. A region of interest spanning the horizontal meridian was defined for analysis of epithelial, host, graft, and total corneal thicknesses. Graft thickness profiles were fit by quadratic polynomials where the 2nd-order coefficients represent the posterior corneal curvature contributed by the graft. The curvature coefficient and central graft thickness were analyzed as predictors of induced refractive error. At final follow-up (mean 5.9 months +/- 3.2 [SD]), 3 patients had a hyperopic shift (+2.50 diopters [D] each), 3 had insignificant (< 0.50 D) refractive shifts, and 1 had a myopic shift. In the group with hyperopic shift, a negative lens effect was predicted by positive curvature coefficients, representing grafts that were thinner centrally than peripherally (mean +22.72 microm/mm(2); range +4.95 to +45.17 microm/mm(2)). In the group with minimal refractive shift, coefficients were less positive (mean +7.28 microm/mm(2); range +2.01 to +13.82 microm/mm(2)). The patient with a myopic shift (-1.00 D) had the only negative curvature coefficient (-0.64 microm/mm(2)). In a 2-predictor model of refractive shift, central graft thickness and the curvature coefficient together accounted for 86% of the variance in the refractive response to DSAEK (P = .025). Nonuniform thickness profiles and variable central graft thicknesses both contribute to refractive shift after DSAEK.
    Journal of Cataract [?] Refractive Surgery 05/2008; 34(4):578-84. · 2.26 Impact Factor
  • Article: Late repeat Descemet-stripping automated endothelial keratoplasty.
    Mark S Gorovoy, David M Meisler, William J Dupps
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    ABSTRACT: To report the outcomes of 2 patients who underwent repeat Descemet-stripping automated endothelial keratoplasty (DSAEK) 13 and 23 months after their primary surgeries. Two patients underwent repeat DSAEK for late graft failure at approximately 1 and 2 years, respectively. The operative procedure involved removing the failed graft and replacing it with new donor tissue. The postoperative visual recovery was similar to the visual outcomes of primary DSAEK surgery, with both patients achieving 20/30 or better best spectacle-corrected visual acuity within 3 months. There were no signs of interface scarring after surgical removal of the failed donor disc. Late repeat DSAEK can result in rapid visual recovery without interface scarring.
    Cornea 03/2008; 27(2):238-40. · 1.73 Impact Factor
  • Article: Reopening of previously closed macular holes after cataract extraction.
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    ABSTRACT: To evaluate the frequency of reopening of macular holes after cataract extraction. Retrospective, comparative, consecutive case series. Two hundred and eleven eyes with idiopathic macular holes closed by vitrectomy were divided into four groups: Group 1: prior cataract extraction; Group 2: vitrectomy then cataract extraction; Group 3: vitrectomy only; and Group 4: vitrectomy and cataract extraction as a combined procedure. The main outcome measure of macular hole reopening was evaluated in relationship to multiple variables. Two hundred and eleven eyes were included: Group 1: 56 eyes; Group 2: 86 eyes; Group 3: 41 eyes; and Group 4: 28 eyes. Twenty-four macular holes reopened (11%) (mean follow-up 26.6 months, range, three to 118 months). The greatest number of macular hole reopenings, 17 (20%), were in Group 2. Cox multivariate analysis failed to demonstrate an association between duration of hole, serum use, internal limiting membrane peeling, or stage and reopening of a macular hole. Cox analysis showed a four-fold increased risk of reopening in Group 2 eyes (95% confidence interval [CI]: 1.7 to 11.2; P = .002). Eyes with cystoid macular edema after cataract extraction had a seven-fold increased risk of macular hole reopening (7.72; 95% CI: 2.79 to 21.3; P < .0005). Kaplan-Meier analysis showed increased rates of macular hole reopening in Group 2 eyes compared to the other 3 groups combined (log-rank P < .00005). Cataract extraction after successful vitrectomy for macular hole, when complicated by cystoid macular edema (CME), may increase the risk of macular hole reopening.
    American Journal of Ophthalmology 09/2007; 144(2):252-9. · 4.22 Impact Factor
  • Article: The fusarium keratitis outbreak: not done yet?
    Archives of Ophthalmology 08/2007; 125(7):981-3. · 3.71 Impact Factor
  • Article: Visual acuity, refractive error, and endothelial cell density six months after Descemet stripping and automated endothelial keratoplasty (DSAEK).
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    ABSTRACT: To evaluate visual acuity, refractive outcomes, and endothelial cell density 6 months after Descemet stripping and automated endothelial keratoplasty (DSAEK). We performed an institutional review board-approved prospective study of a surgical case series of 34 patients at 2 institutions undergoing DSAEK for Fuchs endothelial dystrophy, pseudophakic bullous keratopathy, or aphakic bullous keratopathy with or without simultaneous phacoemulsification and intraocular lens implantation. Clinical outcomes, including best spectacle-corrected visual acuity (BSCVA), spherical equivalent refraction, and refractive astigmatism and topographic or keratometric astigmatism, were assessed at the 6-month postoperative examination and compared with preoperative values with paired Student t tests. The change in endothelial cell density from the eye bank examination to 6 months after transplantation was similarly evaluated. BSCVA averaged 20/99 preoperatively and 20/42 postoperatively (P < 0.0001). After DSAEK, 30 (88.2%) of 34 patients showed improved BSCVA, and 21 (61.8%) of the 34 patients achieved a BSCVA of 20/40 or better. For patients not undergoing simultaneous phacoemulsification and intraocular lens implantation, a hyperopic shift in refraction of 1.19 +/- 1.32 D was noted. Refractive astigmatism, topographic astigmatism, and keratometry showed no statistically significant change. Endothelial cell density of donor corneas averaged 2826 +/- 370 cells/mm, whereas the mean postoperative density was 1396 +/- 440 cells/mm. This finding corresponded to an average loss of 1426 cells/mm (50% loss; P = 0.0001). The first half of cases experienced an average cell loss of 1674 cells/mm (59% loss) compared with 1181 (41% loss) in the second half of cases (P = 0.005). Three (9%) of 34 grafts experienced iatrogenic graft failure and required reoperation with new donor tissue. Also, 9 (27%) of 34 grafts experienced dislocation in the early postoperative period and required repositioning. In this prospective study of DSAEK for bullous keratopathy and Fuchs endothelial corneal dystrophy, improvement of visual acuity was achieved with only a mild tendency toward hyperopic shift and without significant induced astigmatism. Endothelial cell loss was significant, however, and may be related to surgical experience.
    Cornea 07/2007; 26(6):670-4. · 1.73 Impact Factor
  • Article: Use of an air-fluid exchange system to promote graft adhesion during Descemet's stripping automated endothelial keratoplasty.
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    ABSTRACT: Dislocation of the graft is a well-recognized complication of Descemet's stripping automated endothelial keratoplasty (DSAEK). We describe a technique to promote adhesion of the graft during DSAEK using an anterior chamber air-fluid infusion and exchange for direct control of the pressure and medium used to tamponade the graft against the host stroma.
    Journal of Cataract [?] Refractive Surgery 06/2007; 33(5):770-2. · 2.26 Impact Factor
  • Article: Simple technique to unfold the donor corneal lenticule during Descemet's stripping and automated endothelial keratoplasty.
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    ABSTRACT: We describe a technique to facilitate unfolding and prevent inversion of the donor corneal lenticule during Descemet's stripping and automated endothelial keratoplasty (DSAEK). The donor corneal lenticule is unfolded in the anterior chamber using a bent 30-gauge needle on a 3 cc air syringe. The needle tip is used to pinion the edge of the lenticule while an air bubble is simultaneously injected between the folded edges of the donor graft. A gentian-violet dye mark placed on the peripheral stromal surface of the donor lenticule is used to confirm proper graft orientation. The simple technique of simultaneously fixating the donor lenticule while injecting air ensures that the graft unfolds correctly and minimizes potential mechanical trauma to the endothelium.
    Journal of Cataract [?] Refractive Surgery 03/2007; 33(2):189-90. · 2.26 Impact Factor
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    Article: Narrow-strip conjunctival autograft for treatment of pterygium.
    William J Dupps, Bennie H Jeng, David M Meisler
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    ABSTRACT: To determine the efficacy of narrow-strip conjunctival autograft surgery in the treatment of pterygium. Retrospective noncomparative interventional case series. Twenty-one consecutive interventions between 1994 and 2005 in 20 eyes of 18 patients for primary (n = 17 cases) or recurrent (n = 4 cases) pterygia. Surgical excision of the pterygium and conjunctival transplantation with a narrow-strip technique. In all cases, a 2-mm-wide autograft was secured adjacent and posterior to the limbus, leaving a 2- to 3-mm zone of bare sclera between the graft and the anterior margin of the conjunctival wound. All conjunctival margins were secured by suture to bare sclera. Recurrence of pterygium at 12 months. Mean follow-up after surgery was 41 months (median, 42; range, 4-132). At 1 year and all time points thereafter, 18 of 19 (94.7%) cases were free of recurrence. One patient was lost to follow-up at 4 months, and another died after 9 months of follow-up. The lone recurrence occurred inferiorly in an eye that had undergone an adjacent narrow-strip conjunctival transplantation 6 months previously for a recurrent temporal pterygium. The same patient remains recurrence-free 67 months after inferior pterygium excision and a second narrow-strip autograft surgery. Narrow-strip conjunctival autografting appears to be an effective surgical technique in preventing pterygium recurrence. Creating an intervening bare sclera area between the secured conjunctival graft and the anterior margin of the conjunctival wound may be important in preventing recurrence.
    Ophthalmology 03/2007; 114(2):227-31. · 5.45 Impact Factor
  • Article: Dysfunctional tear syndrome: a Delphi approach to treatment recommendations.
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    ABSTRACT: To develop current treatment recommendations for dry eye disease from consensus of expert advice. Of 25 preselected international specialists on dry eye, 17 agreed to participate in a modified, 2-round Delphi panel approach. Based on available literature and standards of care, a survey was presented to each panelist. A two-thirds majority was used for consensus building from responses obtained. Treatment algorithms were created. Treatment recommendations for different types and severity levels of dry eye disease were the main outcome. A new term for dry eye disease was proposed: dysfunctional tear syndrome (DTS). Treatment recommendations were based primarily on patient symptoms and signs. Available diagnostic tests were considered of secondary importance in guiding therapy. Development of algorithms was based on the presence or absence of lid margin disease and disturbances of tear distribution and clearance. Disease severity was considered the most important factor for treatment decision-making and was categorized into 4 levels. Severity was assessed on the basis of tear substitute requirements, symptoms of ocular discomfort, and visual disturbance. Clinical signs present in lids, tear film, conjunctiva, and cornea were also used for categorization of severity. Consensus was reached on treatment algorithms for DTS with and without concurrent lid disease. Panelist opinion relied on symptoms and signs (not tests) for selection of treatment strategies. Therapy is chosen to match disease severity and presence versus absence of lid margin disease or tear distribution and clearance disturbances.
    Cornea 10/2006; 25(8):900-7. · 1.73 Impact Factor
  • Article: Immunohistochemical detection and Western blot analysis of nitrated protein in stored human corneal epithelium.
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    ABSTRACT: While the production of nitric oxide by human corneas in storage has recently been demonstrated, protein nitration as a result of this production has not been demonstrated. In this study, nitrated protein accumulation in the epithelium of stored human corneas was assessed. One half of five donor corneas maintained in storage media for 3 days were prepared for immunohistochemical studies. The other halves remained in storage media for 7 additional days and were also processed for immunohistochemistry. Mouse monoclonal antibody to nitrotyrosine adducts was used to define the localisation of these epitopes. The density of antibody staining was observed and quantified on a digital camera system and statistically analysed. Immunostaining in the epithelium was greater in tissues recovered after 10 days in storage compared to the intensity of staining after 3 days of storage (p<0.0001). No staining was evident in the epithelium in sections exposed to non-immune mouse IgG. Western blot analysis was performed on epithelial cells scraped from corneal surfaces of one-half of four donor corneas in storage for 3 days and from the other half at 10 days of storage. Nitrated BSA was used as a positive control. After extraction and homogenisation, identical protein concentrations of each sample were loaded per lane on 10% gels and subjected to SDS-PAGE. Proteins were blotted and probed with the anti-nitrotyrosine antibody. Western blot immunoreactivity was detected in epithelial samples at the 3 and 10 day recovery times with the latter samples showing greater staining intensity. Nitrated protein, thought to indicate toxic peroxynitrite formation, accumulates in the human corneal epithelium with time of storage. Our study shows that there is an association between increased nitrated protein and storage time.
    Experimental Eye Research 04/2005; 80(4):509-14. · 3.26 Impact Factor
  • Article: A device to facilitate limbal stem cell procurement from eye bank donor tissue for keratolimbal allograft procedures.
    David M Meisler, Victor L Perez, James Proudfit
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    ABSTRACT: To develop a device that facilitates the procurement of corneal limbal stem cell grafts for keratolimbal allograft procedures used in the treatment of ocular surface disease associated with stem cell deficiency. Description of device design and technique for use. The device is composed of a pedestal with a convex surface mounted to a flat platform. A corneoscleral button placed endothelial side down and centrally upon the convexity is secured by suction conveyed through a hollowed core in the pedestal that connects to fenestrated openings on the convex surface. A donut-shaped stainless steel ring placed on tension by springs braces the peripheral tissue. A circular corneal incision is created of a desired thickness by a suction trephine, and a crescent blade is utilized to peripherally dissect a donut-shaped keratolimbal allograft. This device facilitated the harvesting of the keratolimbal allograft tissue from four eye bank donor practice corneoscleral buttons and was then used to successfully procure grafts from six corneoscleral buttons used in three keratolimbal allograft procedures in three patients, one each with aniridia, alkali burn, and drug-induced limbal stem cell deficiency. The described device effectively facilitates procurement of corneoscleral buttons for keratolimbal allograft procedures. It appears to offer advantages over freehanded techniques and previously described devices used for the same purpose.
    American Journal of Ophthalmology 02/2005; 139(1):212-4. · 4.22 Impact Factor
  • Article: Inhibition of nitric oxide synthesis in corneas in storage media.
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    ABSTRACT: The nitrate/nitrite content in storage media was determined after nitric oxide synthase inhibition by adding 400 microl of 100 mm N(G)-monomethyl-l-arginine (LMMA) to four chambers of Optisol GS corneal storage media, each containing one viable human cornea. The companion corneas in storage media without LMMA served as controls. Four hundred microlitre aliquots obtained at baseline (day 0) and at one-day intervals for 20 more days for both groups were analyzed for nitrate and nitrite (breakdown products of nitric oxide) concentration levels using a spectrophotometric method based on the Greiss reaction. Average nitrate/nitrite concentrations, statistically analyzed using a polynomial random coefficients model, showed a statistically significant marked reduction in the levels of nitrate and nitrite accumulation in the study chambers as compared to control chambers for days 1-20(P < 0.001) There was also a reduction in the accumulation rate of nitrate and nitrite concentrations, as compared to controls (P < 0.05) until around day 8 when the differences in rates were no longer statistically significant. The progressive increase in nitrate and nitrite accumulation in corneal storage media can be blunted by the addition of a nitric oxide synthase inhibitor. Given the toxic free radical properties of nitric oxide, corneas in storage awaiting transplantation may benefit from having a nitric oxide synthase inhibitor added to storage media.
    Experimental Eye Research 04/2004; 78(4):891-4. · 3.26 Impact Factor
  • Article: Surgical management of conjunctival lymphangiectasis by conjunctival resection.
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    ABSTRACT: To report the treatment of symptomatic conjunctival lymphangiectasis with conjunctival resection. Interventional case series. Retrospective review of three cases of patients with symptomatic unilateral conjunctival lymphangiectasis who had conjunctival resection of the involved tissue down to bare sclera. The surgical area reepithelialized without recurrence of the lymphatics. In all cases the patients have remained asymptomatic for at least 14 months. Conjunctival resection for symptomatic lymphangiectasis can be a successful therapeutic option for this condition.
    American Journal of Ophthalmology 11/2003; 136(4):735-6. · 4.22 Impact Factor
  • Article: Lymphedema-distichiasis syndrome and FOXC2 gene mutation.
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    ABSTRACT: To describe the clinical characteristics of a family with autosomal dominant lymphedema-distichiasis syndrome and to report the results of analysis of the FOXC2 gene Observational and experimental study. The setting was a clinical practice. The study population was 17 members of a family with lymphedema-distichiasis. Observation procedures were complete ophthalmologic examinations and collection of blood samples. DNA was extracted. Mutation analysis of the coding region of the FOXC2 gene was performed using direct sequencing of polymerase chain reaction (PCR) product and a restriction enzyme assay. The main outcome measure was inheritance of mutation in FOXC2 gene. Nine patients had distichiasis or lymphedema or both and eight did not. Sequencing of the coding region of the only translated exon of the FOXC2 gene revealed a C to A transversion at position 939 resulting in a Tyr313Stop codon with premature termination of translation and a truncated protein product. The mutation was present in all nine affected individuals and in an asymptomatic 9-year-old boy. Distichiasis-lymphedema syndrome results from mutations in FOXC2, a member of the forkhead/winged family of transcription factors. There is intrafamilial variation in the clinical expression of the mutation.
    American Journal of Ophthalmology 11/2002; 134(4):592-6. · 4.22 Impact Factor
  • Article: Nitric oxide generated by corneas in corneal storage media.
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    ABSTRACT: The purpose of the study was to quantify nitric oxide release by human corneal buttons in storage media over time. Group 1 consisted of six chambers of Optisol GS corneal storage media, each containing a viable human corneal button with an attached scleral rim (unsuitable for transplantation), sampled at 1-day intervals for at least 17 days (range, 17-28 days). Group 2 consisted of 34 chambers of Optisol GS media, each used to store a corneal button for penetrating keratoplasty, sampled immediately after each surgery. An unused vial of Optisol GS storage medium was sampled daily for 17 days to serve as a background medium control. The total amount of nitrite and nitrate in each sample was determined by a spectrophotometric method based on the Griess reaction. Data from the daily sampling in group 1 showed that nitrite and nitrate concentrations in storage media containing human corneas increase from a baseline level (beginning at the time the corneas are placed in the media) to an equilibrium concentration of 2.77 microM in a mean time of 6.15 days. Seventy-six percent of the data points from group 2 fell within the 80% predictive interval derived from group 1. No nitrite or nitrate was detected in background medium control samples. The progressive increase in nitrite and nitrate in corneal storage media over time suggests that nitric oxide is continuously released by corneas during storage before transplantation. Given the toxic free radical properties of nitric oxide, corneas in storage media may be subjected to the cumulative toxic effects of nitric oxide.
    Cornea 06/2002; 21(4):410-4. · 1.73 Impact Factor