Dr. Mannis is Professor and Chair of the UC Davis Health System Eye Center. He specializes in corneal transplantation and external diseases of the eye. His research has included development of experimental antimicrobial agents and growth factors that affect the corneal wound healing rate, skin diseases that affect the eye, and outcomes of corneal transplants and artificial corneas. Dr. Mannis has authored over 125 publications and five books on topics relating to corneal surgery and disease.
Effectiveness of Intrastromal Corneal Ring Implantation in the Treatment of Adult Patients With Keratoconus: A Systematic Review.
J Refract Surg. 2019 Mar 01;35(3):191-200
Authors: Izquierdo L, Mannis MJ, Mejías Smith JA, Henriquez MA
PURPOSE: To evaluate the available evidence on the effectiveness of intrastromal corneal rings (ICRs) in the treatment of adults with keratoconus.
METHODS: A systematic review of electronic databases was completed through July 30, 2017. All primary research articles in which adults with keratoconus were treated with ICRs were included. Two independent reviewers assessed methodological quality and classified the studies into high, low, or undefined risk of bias. The measured variables assessed were visual acuity, refraction, keratometry, ring type, and complications.
RESULTS: The initial search yielded 442 scientific articles, 62 articles were read extensively, and 18 articles were assessed for eligibility and included for statistical analysis and quality assessment. A total of 1,325 eyes were analyzed, and the results were evaluated preoperatively and at 12 months of follow-up. Uncorrected distance visual acuity (UDVA) improved 0.23 ± 0.28 logMAR and corrected distance visual acuity (CDVA) improved 0.06 ± 0.21 logMAR. Sphere improved 2.81 ± 1.54 diopters (D), cylinder improved 1.49 ± 0.83 D, and mean keratometry improved 3.41 ± 2.13 D within 12 months of follow-up. ICR implantation combined with corneal crosslinking improved UDVA, refraction, and keratometry to a greater degree than ICR implantation alone.
CONCLUSIONS: The studies analyzed demonstrate refractive and visual improvement of patients treated with the ICR implantation technique. However, description of the methodological process necessary to evaluate the bias effectively is insufficient. [J Refract Surg. 2019;35(3):191-200.].
PMID: 30855097 [PubMed - in process]
Evaluation of a Portable Artificial Vision Device Among Patients With Low Vision.
JAMA Ophthalmol. 2016 Jul 01;134(7):748-52
Authors: Moisseiev E, Mannis MJ
IMPORTANCE: Low vision is irreversible in many patients and constitutes a disability. When no treatment to improve vision is available, technological developments aid these patients in their daily lives.
OBJECTIVE: To evaluate the usefulness of a portable artificial vision device (OrCam) for patients with low vision.
DESIGN, SETTING, AND PARTICIPANTS: A prospective pilot study was conducted between July 1 and September 30, 2015, in a US ophthalmology department among 12 patients with visual impairment and best-corrected visual acuity of 20/200 or worse in their better eye.
INTERVENTIONS: A 10-item test simulating activities of daily living was used to evaluate patients' functionality in 3 scenarios: using their best-corrected visual acuity with no low-vision aids, using low-vision aids if available, and using the portable artificial vision device. This 10-item test was devised for this study and is nonvalidated. The portable artificial vision device was tested at the patients' first visit and after 1 week of use at home.
MAIN OUTCOMES AND MEASURES: Scores on the 10-item daily function test.
RESULTS: Among the 12 patients, scores on the 10-item test improved from a mean (SD) of 2.5 (1.6) using best-corrected visual acuity to 9.5 (0.5) using the portable artificial vision device at the first visit (mean difference, 7.0; 95% CI, 6.0-8.0; P < .001) and 9.8 (0.4) after 1 week (mean difference from the first visit, 7.3; 95% CI, 6.3-8.3; P < .001). Mean (SD) scores with the portable artificial vision device were also better in the 7 patients who used other low-vision aids (9.7 [0.5] vs 6.0 [2.6], respectively; mean difference, 3.7; 95% CI, 1.5-5.9; P = .01).
CONCLUSIONS AND RELEVANCE: When patients used a portable artificial vision device, an increase in scores on a nonvalidated 10-item test of activities of daily living was seen. Further evaluations are warranted to determine the usefulness of this device among individuals with low vision.
PMID: 27148909 [PubMed - in process]
In vivo ocular imaging of the cornea of the normal female laboratory beagle using confocal microscopy.
Vet Ophthalmol. 2015 Mar 6;
Authors: Strom AR, Cortés DE, Thomasy SM, Kass PH, Mannis MJ, Murphy CJ
OBJECTIVE: To obtain normative data for the normal laboratory beagle cornea using high-resolution in vivo confocal microscopy (IVCM).
ANIMALS STUDIED: Sixteen eyes of eight healthy young female intact beagles.
PROCEDURES: The central cornea was imaged using IVCM. Mixed effects linear regression was used for statistical analysis.
RESULTS: in vivo confocal microscopy allowed detailed visualization and quantification of epithelial cells (superficial epithelial cell diameter: 43.25 ± 6.64 μm, basal cell diameter: 4.43 ± 0.67 μm), and nerve fibers (subepithelial nerve fiber diameter: 2.38 ± 0.69 μm, anterior stromal nerve fiber diameter: 16.93 ± 4.55 μm). Keratocyte density (anterior stroma 993.38 ± 134.24 cells/mm(2) , posterior stroma 789.38 ± 87.13 cells/mm(2) ) and endothelial cell density (2815.18 ± 212.59 cells/mm(2) ) were also measured.
CONCLUSION: High-resolution IVCM provides detailed noninvasive evaluation of the cornea in the normal laboratory beagle.
PMID: 25752331 [PubMed - as supplied by publisher]
In vivo evaluation of the cornea and conjunctiva of the normal laboratory beagle using time- and Fourier-domain optical coherence tomography and ultrasound pachymetry.
Vet Ophthalmol. 2015 Feb 10;
Authors: Strom AR, Cortés DE, Rasmussen CA, Thomasy SM, McIntyre K, Lee SF, Kass PH, Mannis MJ, Murphy CJ
OBJECTIVE: To obtain normative data for the canine cornea and conjunctiva using high-resolution time- and Fourier-domain optical coherence tomography (TD-OCT and FD-OCT) and ultrasound pachymetry (USP).
ANIMALS: One hundred sixty-eight eyes of 133 healthy young intact laboratory beagles.
PROCEDURES: The cornea and conjunctiva of 16 eyes of 8 healthy young intact female beagles were imaged using FD-OCT. Corneal thickness was measured with FD-OCT and USP, while corneal epithelial thickness and conjunctival epithelial thickness were measured with FD-OCT. The central corneal thickness (CCT) was determined in 152 eyes of 125 healthy young adult intact female (35) and male (90) beagles using TD-OCT. Mixed effects linear regression was used for statistical analysis.
RESULTS: The CCT was (mean ± standard deviation) 497.54 ± 29.76, 555.49 ± 17.19, and 594.81 ± 33.02 μm as measured by FD-OCT, USP, and TD-OCT, respectively. The central, superior paraxial, superior perilimbal corneal epithelial thickness and superior bulbar conjunctival epithelial thickness were 52.38 ± 7.27, 56.96 ± 6.47, 69.06 ± 8.84 and 42.98 ± 6.17 μm, respectively. When comparing techniques used for measuring CCT (USP vs. FD-OCT and FD-OCT vs. TD-OCT), USP and TD-OCT generated significantly greater values in comparison with FD-OCT (both P < 0.001). For all dogs, CCT increased with increasing age and body weight (both P < 0.001) and was higher in intact males vs. females using TD-OCT (P = 0.034).
CONCLUSION: High-resolution FD-OCT and TD-OCT provide detailed noninvasive evaluation of in vivo canine anterior segment structures. Normative values of the canine cornea and conjunctiva are reported.
PMID: 25676065 [PubMed - as supplied by publisher]
Corneal graft rejection 10 years after penetrating keratoplasty in the cornea donor study.
Cornea. 2014 Oct;33(10):1003-9
Authors: Dunn SP, Gal RL, Kollman C, Raghinaru D, Dontchev M, Blanton CL, Holland EJ, Lass JH, Kenyon KR, Mannis MJ, Mian SI, Rapuano CJ, Stark WJ, Beck RW, Writing Committee for the Cornea Donor Study Research Group
PURPOSE: The aim of this study was to assess the effect of donor and recipient factors on corneal allograft rejection and evaluate whether a rejection event was associated with graft failure.
METHODS: One thousand ninety subjects undergoing penetrating keratoplasty for a moderate risk condition (principally Fuchs dystrophy or pseudophakic corneal edema) were followed for up to 12 years. Associations of baseline recipient and donor factors with the occurrence of a rejection event were assessed in univariate and multivariate proportional hazards models.
RESULTS: Among 651 eyes with a surviving graft at 5 years, the 10-year graft failure (±99% confidence interval) rates were 12% ± 4% among eyes with no rejection events in the first 5 years, 17% ± 12% in eyes with at least 1 probable, but no definite rejection event, and 22% ± 20% in eyes with at least 1 definite rejection event. The only baseline factor significantly associated with a higher risk of definite graft rejection was a preoperative history of glaucoma, particularly when previous glaucoma surgery had been performed and glaucoma medications were being used at the time of transplant (10-year incidence 35% ± 23% compared with 14% ± 4% in eyes with no history of glaucoma/intraocular pressure treatment, P = 0.008).
CONCLUSIONS: Patients who experienced a definite rejection event frequently developed graft failure raising important questions as to how we might change acute and long-term corneal graft management. Multivariate analysis indicated that previous use of glaucoma medications and glaucoma filtering surgery was a significant risk factor related to a definite rejection event.
PMID: 25119961 [PubMed - indexed for MEDLINE]
Professor Dr Med Oskar Fehr: the fate of an outstanding German-Jewish ophthalmologist: an early contributor to cornea and external disease.
Cornea. 2014 Aug;33(8):860-4
Authors: Lisch W, Mannis MJ
PURPOSE: The aim of this study was to recount the immense and abrupt change in the private and professional life of a prominent German-Jewish ophthalmologist in the transition from democracy to dictatorship in Germany during the first half of the 20th century.
METHODS: This involves a Retrospective analysis of Fehr's clinical and scientific work as the first assistant of Julius Hirschberg's world-famous eye clinic in Berlin; evaluation of Fehr's successful tenure as a chair of Virchow's Eye Hospital; the catastrophic influence of Hitler's seizure of power on the private and professional lives of German-Jewish physicians; and an analysis of Fehr's personal and professional will to continue the practice of medicine in England.
RESULTS: Oskar Fehr published >50 articles and was the first to describe the endemic swimming pool conjunctivitis. He was the first to specifically distinguish granular, lattice, and macular corneal dystrophies. Professor Oskar Fehr was the chair of one of the most important eye clinics in Germany for nearly 30 years. The "Anti-Jewish Medical Laws" with their terrible consequences on private and professional lives led to Fehr's emigration from his homeland to England in 1939. He obtained a British medical doctor degree after 4 years of study, and at an advanced age, he demonstrated his determination to practice ophthalmology successfully in London. Oskar Fehr died in London on August 1, 1959.
PMID: 25000141 [PubMed - indexed for MEDLINE]
Interfacial phenomena and the ocular surface.
Ocul Surf. 2014 Jul;12(3):178-201
Authors: Yañez-Soto B, Mannis MJ, Schwab IR, Li JY, Leonard BC, Abbott NL, Murphy CJ
Ocular surface disorders, such as dry eye disease, ocular rosacea, and allergic conjunctivitis, are a heterogeneous group of diseases that require an interdisciplinary approach to establish underlying causes and develop effective therapeutic strategies. These diverse disorders share a common thread in that they involve direct changes in ocular surface chemistry as well as the rheological properties of the tear film and topographical attributes of the cellular elements of the ocular surface. Knowledge of these properties is crucial to understand the formation and stability of the preocular tear film. The study of interfacial phenomena of the ocular surface flourished during the 1970s and 1980s, but after a series of lively debates in the literature concerning distinctions between the epithelial and the glandular origin of ocular surface disorders during the 1990s, research into this important topic has declined. In the meantime, new tools and techniques for the characterization and functionalization of biological surfaces have been developed. This review summarizes the available literature regarding the physicochemical attributes of the ocular surface, analyzes the role of interfacial phenomena in the pathobiology of ocular surface disease, identifies critical knowledge gaps concerning interfacial phenomena of the ocular surface, and discusses the opportunities for the exploitation of these phenomena to develop improved therapeutics for the treatment of ocular surface disorders.
PMID: 24999101 [PubMed - indexed for MEDLINE]
Simultaneous surgery for corneal edema and aphakia: DSEK and placement of a retropupillary iris claw lens.
Cornea. 2014 Feb;33(2):197-200
Authors: Vélez F M, Mannis MJ, Izquierdo L, Sánchez JG, Velásquez LF, Rojas S
PURPOSE: The aim was to report the surgical outcomes of simultaneous Descemet stripping endothelial keratoplasty (DSEK) with a retropupillary fixated iris claw lens in patients with aphakic corneal edema without capsular support.
METHODS: The clinical records of aphakic patients with corneal edema and no capsular support who underwent a combined DSEK and implantation of a retropupillary fixated iris claw lens (Artisan) were evaluated. Presurgical and postsurgical best-corrected visual acuity, postsurgical refraction, and endothelial cell count were analyzed at the first and sixth months after the surgery and were imaged with anterior segment ultrasound biomicroscopy.
RESULTS: A total of 9 eyes from 7 females and 2 males were analyzed. The average age was 72.1 years. The mean duration of the postoperative follow-up was 7.7 months. All the patients achieved corrected visual acuities over 0.60 logarithm of the minimum angle of resolution. There was no significant variation in the endothelial count between the first and sixth months. Astigmatism >1 D was induced in all the patients, with 7 patients having against the rule, and 2 patients having oblique astigmatism.
CONCLUSIONS: DSEK combined with a retropupillary fixated iris claw lens was shown to be a safe surgical technique in patients with aphakia without capsular support and corneal swelling. This surgery resulted in stable endothelial cell counts during the first 6 months after the surgery and an improvement in visual acuity.
PMID: 24322799 [PubMed - indexed for MEDLINE]
Donor age and factors related to endothelial cell loss 10 years after penetrating keratoplasty: Specular Microscopy Ancillary Study.
Ophthalmology. 2013 Dec;120(12):2428-35
Authors: Writing Committee for the Cornea Donor Study Research Group, Lass JH, Benetz BA, Gal RL, Kollman C, Raghinaru D, Dontchev M, Mannis MJ, Holland EJ, Chow C, McCoy K, Price FW, Sugar A, Verdier DD, Beck RW
OBJECTIVE: To examine the effect of donor age and other perioperative factors on long-term endothelial cell loss after penetrating keratoplasty (PKP).
DESIGN: Multicenter, prospective, double-masked clinical trial.
PARTICIPANTS: We included 176 participants from the Cornea Donor Study cohort who had not experienced graft failure ≥ 10 years after PKP for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema).
METHODS: Corneas from donors 12 to 75 years old were assigned to participants using a randomized approach, without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines. Images of the central endothelium were obtained preoperatively and at intervals for 10 years postoperatively. Images were analyzed by a central image analysis reading center to determine endothelial cell density (ECD).
MAIN OUTCOME MEASURES: Endothelial cell density at 10 years.
RESULTS: Among study participants with a clear graft at 10 years, the 125 who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 76%, resulting in a 10-year median ECD of 628 cells/mm(2) (interquartile range [IQR], 522-850 cells/mm(2)), whereas the 51 who received a cornea from a donor 66 to 75 years old experienced a cell loss of 79%, resulting in a median 10-year ECD of 550 cells/mm(2) (IQR, 483-694 cells/mm(2); P adjusted for baseline ECD = 0.03). In addition to younger donor age, higher ECD values were significantly associated with higher baseline ECD (P<0.001) and larger donor tissue size (P<0.001). Forty-two of the 176 participants (24%) had an ECD of <500 cells/mm(2) at 10 years and only 24 (14%) had an ECD of >1000 cells/mm(2).
CONCLUSIONS: Substantial cell loss occurs in eyes with a clear graft 10 years after PKP, with the rate of cell loss being slightly greater with older donor age. Greater preoperative ECD and larger donor tissue size are associated with higher ECD at 10 years.
PMID: 24246826 [PubMed - indexed for MEDLINE]
The effect of donor age on penetrating keratoplasty for endothelial disease: graft survival after 10 years in the Cornea Donor Study.
Ophthalmology. 2013 Dec;120(12):2419-27
Authors: Writing Committee for the Cornea Donor Study Research Group, Mannis MJ, Holland EJ, Gal RL, Dontchev M, Kollman C, Raghinaru D, Dunn SP, Schultze RL, Verdier DD, Lass JH, Raber IM, Sugar J, Gorovoy MS, Sugar A, Stulting RD, Montoya MM, Penta JG, Benetz BA, Beck RW
OBJECTIVE: To determine whether the 10-year success rate of penetrating keratoplasty for corneal endothelial disorders is associated with donor age.
DESIGN: Multicenter, prospective, double-masked clinical trial.
PARTICIPANTS: A total of 1090 participants undergoing penetrating keratoplasty at 80 sites for Fuchs' dystrophy (62%), pseudophakic/aphakic corneal edema (34%), or another corneal endothelial disorder (4%) and followed for up to 12 years.
METHODS: Forty-three eye banks provided corneas from donors aged 12 to 75 years, using a randomized approach to assign donor corneas to study participants without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines.
MAIN OUTCOME MEASURES: Graft failure defined as a regraft or, in the absence of a regraft, a cloudy cornea that was sufficiently opaque to compromise vision for 3 consecutive months.
RESULTS: In the primary analysis, the 10-year success rate was 77% for 707 corneas from donors aged 12 to 65 years compared with 71% for 383 donors aged 66 to 75 years (difference, +6%; 95% confidence interval, -1 to +12; P = 0.11). When analyzed as a continuous variable, higher donor age was associated with lower graft success beyond the first 5 years (P<0.001). Exploring this association further, we observed that the 10-year success rate was relatively constant for donors aged 34 to 71 years (75%). The success rate was higher for 80 donors aged 12 to 33 years (96%) and lower for 130 donors aged 72 to 75 years (62%). The relative decrease in the success rate with donor ages 72 to 75 years was not observed until after year 6.
CONCLUSIONS: Although the primary analysis did not show a significant difference in 10-year success rates comparing donor ages 12 to 65 years and 66 to 75 years, there was evidence of a donor age effect at the extremes of the age range. Because we observed a fairly constant 10-year success rate for donors aged 34 to 71 years, which account for approximately 75% of corneas in the United States available for transplant, the Cornea Donor Study results indicate that donor age is not an important factor in most penetrating keratoplasties for endothelial disease.
PMID: 24246825 [PubMed - indexed for MEDLINE]
Evaluation of microbial flora in eyes with a Boston type 1 Keratoprosthesis.
Cornea. 2013 Dec;32(12):1537-9
Authors: Lee SH, Mannis MJ, Shapiro B, Li JY, Polage C, Smith W
PURPOSE: To evaluate the microbial flora of eyes with a Boston Keratoprosthesis (K-Pro).
METHODS: A prospective study was performed for 17 eyes of 15 patients who underwent a K-Pro implantation between September 2005 and June 2011. Preoperative diagnoses included failed corneal grafts, limbal stem cell deficiency, chemical burns, and Stevens-Johnson Syndrome. The patients used topical antibiotics after their surgery including a fluoroquinolone, polymyxin-trimethoprim, vancomycin, or a combination of the 3. The conjunctiva in the study eye was swabbed and cultured. A separate culture was taken of the contralateral eye as well. If available, the bandage contact lens was removed, and half of it was placed in thioglycolate broth, and half in 5 mL of a sterile balanced salt solution. The contact lens in the balanced salt solution was sonicated using a QSonica Q125 sonicator (Newtown, CT) for 1 minute, at an amplitude of 20%. Ten microliters of fluid was subsequently cultured.
RESULTS: Of the patients who underwent the K-Pro surgery during that time period, 15 patients with 17 eyes were able to participate in the data collection. Nine of the 17 eyes implanted with the K-Pro (53%) had positive cultures. Two of the 13 (15%) of the control swabs exhibited bacterial growth. Eight percent (1/12) of the sonicated lenses were positive on culture, whereas 4/12 (33%) of the lenses placed in thioglycolate broth were positive for organisms.
CONCLUSIONS: Despite being on antibiotics, eyes implanted with the K-Pro were more likely to have a positive conjunctival culture in our cohort as compared with that of fellow eyes.
PMID: 24145635 [PubMed - indexed for MEDLINE]
Ocular rosacea: common and commonly missed.
J Am Acad Dermatol. 2013 Dec;69(6 Suppl 1):S36-41
Authors: Vieira AC, Mannis MJ
Rosacea is a prevalent disorder that may be disfiguring and cause significant ocular morbidity, if not diagnosed and managed appropriately. Ocular rosacea, in particular, is often left undiagnosed as no specific test is available to confirm the diagnosis. Accurate diagnosis is further complicated because symptoms of ocular rosacea are not always specific to the disorder alone. Other ophthalmic disorders may present with similar findings. Further challenges exist because the severity of ocular symptoms is often not related to the severity of cutaneous findings in rosacea. Isolating a disease marker may facilitate earlier diagnosis and treatment, and could also contribute to better understanding of disease pathogenesis. The glycomics of tear fluid and saliva in patients with rosacea shows promise as an initial step in the search for a biomarker specific to the disease. We have previously found potentially important disease biomarkers in roseatic tear and saliva samples. Further investigation should prove important in the early stages of developing a set of markers for accurate disease identification.
PMID: 24229635 [PubMed - indexed for MEDLINE]
Epithelial downgrowth after penetrating keratoplasty: imaging by high-resolution optical coherence tomography and in vivo confocal microscopy.
Cornea. 2013 Nov;32(11):1505-8
Authors: Chen MC, Cortés DE, Harocopos G, Mannis MJ
PURPOSE: To report the clinical utility of high-resolution anterior segment optical coherence tomography (AS-OCT) combined with in vivo confocal microscopy (IVCM) to diagnose and follow the effectiveness of treatment of 2 cases of epithelial downgrowth after penetrating keratoplasty.
METHODS: A retrospective case review was performed on 2 eyes of 2 patients with a history of multiple penetrating keratoplasties that developed epithelial downgrowth 4 and 6 months after the most recent penetrating graft. At various time points, high-resolution AS-OCT images were obtained using the Spectralis (Heidelberg Engineering GmbH), and IVCM images were obtained using the Heidelberg Retina Tomograph III Rostock Cornea Module (Heidelberg Engineering GmbH). In 1 case, the diagnosis was confirmed by histopathologic evaluation.
RESULTS: Two patients developed epithelial downgrowth after penetrating keratoplasty. In case 1, a 48-year-old man with a history of Acanthamoeba keratitis developed epithelial downgrowth after undergoing 2 therapeutic grafts over a 1-year period. In case 2, a 40-year-old man with a history of a corneal laceration complicated by fungal keratitis was diagnosed with epithelial downgrowth after undergoing 3 penetrating grafts, the placement of a glaucoma drainage device, and a pars plana vitrectomy over a 3-year period. In both cases, at the level of the endothelium, AS-OCT identified a highly reflective layer and IVCM revealed round hyperreflective nuclei consistent with epithelium.
CONCLUSIONS: Epithelial downgrowth is an uncommon complication after penetrating keratoplasty. High-resolution AS-OCT and IVCM are noninvasive imaging modalities that may potentially be more sensitive in identifying and monitoring epithelial downgrowth than routine light biomicroscopy and may obviate the need for invasive diagnostic measures.
PMID: 23928949 [PubMed - indexed for MEDLINE]
Eye banking and corneal transplantation communicable adverse incidents: current status and project NOTIFY.
Cornea. 2013 Aug;32(8):1155-66
Authors: Dubord PJ, Evans GD, Macsai MS, Mannis MJ, Glasser DB, Strong DM, Noël L, Fehily D
PURPOSE: Evidence of the transmission of disease via donor ocular tissue has been demonstrated for adenocarcinoma, rabies, hepatitis B virus, cytomegalovirus, herpes simplex virus, Creutzfeldt-Jakob disease, and a variety of bacterial and fungal infections.
METHODS: Although there is no evidence to date of disease transmission for HIV infection, syphilis, hepatitis C, hepatitis A, tuberculosis, HTLV-1 and -2 infection, active leprosy, active typhoid, smallpox, and active malaria, these entities remain contraindications for transplantation for all eye banks nationally and internationally. The potential sources of contamination include infected donors, during the process of removing tissue from cadaveric donors, the processing environment, and contaminated supplies and reagents used during processing. The transmissions of Herpes simplex virus and HSV via corneal graft have been shown to be responsible for primary graft failure. HSV-1 may also be an important cause of PFG.
RESULTS: The long latency period of some diseases, the emergence of new infectious disease, and the reemergence of others emphasize the need for long-term record maintenance and effective tracing capabilities.
CONCLUSIONS: The standardization of definitions for adverse events and reactions will be necessary to support the prevention and transmission of disease. International classification of a unique identification system for donors will be increasingly important for vigilance and traceability in cross-national exportation of human cells, tissues, and cellular- and tissue-based products. Opportunities for continuous improvement exist as does the need for constant vigilance and surveillance.
PMID: 23676781 [PubMed - indexed for MEDLINE]
Three-dimensional anterior segment imaging in patients with type 1 Boston Keratoprosthesis with switchable full depth range swept source optical coherence tomography.
J Biomed Opt. 2013 Aug;18(8):86002
Authors: Poddar R, Raju P, Cortés DE, Werner JS, Mannis MJ, Zawadzki RJ
A high-speed (100 kHz A-scans/s) complex conjugate resolved 1 μm swept source optical coherence tomography (SS-OCT) system using coherence revival of the light source is suitable for dense three-dimensional (3-D) imaging of the anterior segment. The short acquisition time helps to minimize the influence of motion artifacts. The extended depth range of the SS-OCT system allows topographic analysis of clinically relevant images of the entire depth of the anterior segment of the eye. Patients with the type 1 Boston Keratoprosthesis (KPro) require evaluation of the full anterior segment depth. Current commercially available OCT systems are not suitable for this application due to limited acquisition speed, resolution, and axial imaging range. Moreover, most commonly used research grade and some clinical OCT systems implement a commercially available SS (Axsun) that offers only 3.7 mm imaging range (in air) in its standard configuration. We describe implementation of a common swept laser with built-in k-clock to allow phase stable imaging in both low range and high range, 3.7 and 11.5 mm in air, respectively, without the need to build an external MZI k-clock. As a result, 3-D morphology of the KPro position with respect to the surrounding tissue could be investigated in vivo both at high resolution and with large depth range to achieve noninvasive and precise evaluation of success of the surgical procedure.
PMID: 23912759 [PubMed - indexed for MEDLINE]
High-resolution spectral domain anterior segment optical coherence tomography in type 1 Boston keratoprosthesis.
Cornea. 2013 Jul;32(7):951-5
Authors: Shapiro BL, Cortés DE, Chin EK, Li JY, Werner JS, Redenbo E, Mannis MJ
PURPOSE: To report the results of imaging using high-resolution, Fourier domain anterior segment optical coherence tomography (AS-OCT) to evaluate patients with a type 1 Boston Keratoprosthesis (KPro).
METHODS: We performed a retrospective comparative study of patients in whom we implanted the Boston KPro. A total of 26 eyes of 23 patients from the Cornea Service at the University of California Davis Eye Center were included. Subjects were evaluated with the Spectralis AS-OCT (Heidelberg Engineering GmbH).
RESULTS: Preoperative diagnoses for KPro surgery included failed corneal transplant (69%), chemical burn (23%), and aniridia (8%). The average age of patients was 63.2 years (range, 17-88 years). Fifty-four percent of the patients were female. The mean duration between the KPro surgery and the acquisition of high-resolution AS-OCT imaging was 35.8 months (range, 2-90 months). The most commonly observed finding was retroprosthetic membrane formation, which we found in 77% of KPro eyes. In 65% of KPro eyes, we identified epithelium behind the front plate, and in 54%, we identified an epithelial lip over the anterior surface of the KPro front plate. In 31% of KPro eyes, we identified periprosthetic cysts, gaps or spaces, and thinning in the corneal carrier graft.
CONCLUSIONS: Fourier domain AS-OCT is a useful noninvasive imaging technique in patients with a KPro and provides the ability to identify changes that are sometimes difficult to appreciate by clinical evaluation. The higher resolution Fourier domain systems may aid in the clinical diagnosis and management of pathology that might not be imaged with instruments of lower resolution. AS-OCT has the potential for monitoring the anatomic stability of an implanted KPro and may also help to monitor for complications. Moreover, high-resolution imaging may enhance our understanding of periprosthetic anatomy.
PMID: 23591146 [PubMed - indexed for MEDLINE]
Standard terminology and labeling of ocular tissue for transplantation.
Cornea. 2013 Jun;32(6):725-8
Authors: Armitage WJ, Ashford P, Crow B, Dahl P, DeMatteo J, Distler P, Gopinathan U, Madden PW, Mannis MJ, Moffatt SL, Ponzin D, Tan D
PURPOSE: To develop an internationally agreed terminology for describing ocular tissue grafts to improve the accuracy and reliability of information transfer, to enhance tissue traceability, and to facilitate the gathering of comparative global activity data, including denominator data for use in biovigilance analyses.
METHODS: ICCBBA, the international standards organization for terminology, coding, and labeling of blood, cells, and tissues, approached the major Eye Bank Associations to form an expert advisory group. The group met by regular conference calls to develop a standard terminology, which was released for public consultation and amended accordingly.
RESULTS: The terminology uses broad definitions (Classes) with modifying characteristics (Attributes) to define each ocular tissue product. The terminology may be used within the ISBT 128 system to label tissue products with standardized bar codes enabling the electronic capture of critical data in the collection, processing, and distribution of tissues. Guidance on coding and labeling has also been developed.
CONCLUSIONS: The development of a standard terminology for ocular tissue marks an important step for improving traceability and reducing the risk of mistakes due to transcription errors. ISBT 128 computer codes have been assigned and may now be used to label ocular tissues. Eye banks are encouraged to adopt this standard terminology and move toward full implementation of ISBT 128 nomenclature, coding, and labeling.
PMID: 23538627 [PubMed - indexed for MEDLINE]
Anterior segment OCT and confocal microscopy findings in atypical corneal intraepithelial neoplasia.
Cornea. 2013 Jun;32(6):875-9
Authors: Chin EK, Cortés DE, Lam A, Mannis MJ
PURPOSE: To report a case of biopsy-proven corneal intraepithelial neoplasia (CIN) diagnosed and followed clinically using high-resolution anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM).
METHODS: Observational case report.
RESULTS: A 57-year-old man presented with decreased vision in the right eye for 2 months before presentation. His best-corrected visual acuity was 20/70 in the affected eye, and the slit-lamp examination revealed superficial opacification of the anterior cornea originating from the temporal limbus with a "leopard-spot" pattern more centrally. The lesion was excised at his 2-month follow-up, and the histological examination revealed squamous dysplasia consistent with CIN. Visual acuity improved, and the slit-lamp examination revealed barely visible residual disease at the temporal limbus. However, AS-OCT showed a thicker and highly reflective epithelial layer near the temporal limbus, similar to initial presentation, highlighting this residual disease. IVCM demonstrated dysplastic cells consistent with residual disease. Therefore, we treated the patient with topical interferon alpha-2b (1 million IU/mL) 4 times daily in the affected eye. At 3-month follow-up, the patient's best-corrected visual acuity was 20/20 in the affected eye with persistent but improved residual disease adjacent to the temporal limbus. In the mid-periphery of the inferonasal cornea, focal areas of iatrogenic linear scarring were confirmed to be limited to the anterior stroma by AS-OCT and IVCM at 6-month follow-up.
CONCLUSIONS: AS-OCT and IVCM are noninvasive techniques that can be used to diagnose and aid in the management of CIN, which may present as subclinical disease through slit-lamp biomicroscopy alone.
PMID: 23538623 [PubMed - indexed for MEDLINE]
Corneal thickness as a predictor of corneal transplant outcome.
Cornea. 2013 Jun;32(6):729-36
Authors: Verdier DD, Sugar A, Baratz K, Beck R, Dontchev M, Dunn S, Gal RL, Holland EJ, Kollman C, Lass JH, Mannis MJ, Penta J, Cornea Donor Study Investigator Group
PURPOSE: To assess corneal thickness (CT) and correlation with graft outcome after penetrating keratoplasty in the Cornea Donor Study.
METHODS: A total of 887 subjects with a corneal transplant for a moderate-risk condition (principally Fuchs dystrophy or pseudophakic corneal edema) had postoperative CT measurements throughout a 5-year follow-up time. Relationships between baseline (recipient, donor, and operative) factors and CT were explored. Proportional hazards models were used to assess the association between CT and graft failure. Relationship between CT and cell density was assessed with a longitudinal repeated measures model and Spearman correlation estimates.
RESULTS: Higher longitudinal CT measurements were associated with the following: diagnosis of pseudophakic or aphakic corneal edema (P < 0.001), intraocular pressure >25 mm Hg during the first postoperative month (P = 0.003), white (non-Hispanic) donor race (P = 0.002), and respiratory causes of donor death (P < 0.001). Among those without graft failure within the first postoperative year, the 5-year cumulative incidence (± 95% confidence interval) of graft failure was 5% ± 5% in those with a 1-year CT ≤ 500 μm, 5% ± 3% for CT 501 to 550 μm, 7% ± 4% for CT 551 to 600 μm, and 20% ± 11% for CT >600 μm. In a multivariate analysis, both 1-year CT and cell density were associated with subsequent graft failure (P = 0.002 and 0.009). CT increase was modestly associated with endothelial cell loss during follow-up (r = -0.29).
CONCLUSIONS: During the first 5 years after penetrating keratoplasty, CT can serve as a predictor of graft survival. However, CT is not a substitute for cell density measurement because both measures were independently predictive of graft failure.
PMID: 23343949 [PubMed - indexed for MEDLINE]
Intereye asymmetry detected by Scheimpflug imaging in subjects with normal corneas and keratoconus.
Cornea. 2013 Jun;32(6):779-82
Authors: Henriquez MA, Izquierdo L, Mannis MJ
PURPOSE: To report the intereye asymmetry with regard to pachymetry and corneal elevation variables in subjects with normal corneas and in those with keratoconus.
METHODS: This is a prospective study that included 151 patients who had Pentacam imaging in both eyes: 53 subjects with bilateral normal corneas and 98 with bilateral keratoconus. Central corneal thickness (CCT), pachymetry at the thinnest point (TP), posterior elevation at the thinnest point of the cornea (PETP), distance, volume, and differential pachymetry were measured. Intereye asymmetry was determined by subtracting the lowest value from the highest value for each variable. The degree of asymmetry between each subject's eyes was calculated with intraclass correlation coefficients for all the variables. Receiver operating characteristic curve was used to determine predictive accuracy and to identify optimal cutoffs of these values.
RESULTS: In the normal subjects, the mean intereye asymmetries in CCT, TP, and PETP were 10.28, 11.04, and 3.75 μm, respectively. In the keratoconic patients, the mean intereye asymmetries in CCT, TP, and PETP were 25.89, 30.15, and 20.08 μm, respectively. Normal eyes demonstrated the smallest difference between eyes, compared with the keratoconic eyes, in all of the variables analyzed (P < 0.05). A cutoff value of 6.5 μm in the mean intereye asymmetry at the posterior elevation had an area under the receiver operating characteristic curve of 0.91.
CONCLUSIONS: There is a greater intereye asymmetry in pachymetry and posterior corneal elevation variables in keratoconic patients than in subjects with normal corneas.
PMID: 23263222 [PubMed - indexed for MEDLINE]
Endothelial morphometric measures to predict endothelial graft failure after penetrating keratoplasty.
JAMA Ophthalmol. 2013 May;131(5):601-8
Authors: Benetz BA, Lass JH, Gal RL, Sugar A, Menegay H, Dontchev M, Kollman C, Beck RW, Mannis MJ, Holland EJ, Gorovoy M, Hannush SB, Bokosky JE, Caudill JW, Cornea Donor Study Investigator Group
IMPORTANCE: Endothelial morphometric measures have potential value in predicting graft failure after penetrating keratoplasty.
OBJECTIVE: To determine whether preoperative and/or postoperative central morphometric measures (endothelial cell density [ECD], coefficient of variation [CV], and percentage of hexagonality [HEX]) and their postoperative changes are predictive of graft failure caused by endothelial decompensation after penetrating keratoplasty to treat a moderate-risk condition, principally Fuchs dystrophy or pseudophakic corneal edema.
DESIGN: In a subset of Cornea Donor Study participants with graft failure, a central reading center determined preoperative and postoperative ECD, CV, and HEX from available central endothelial specular images.
SETTING: Cornea Image Analysis Reading Center of the Specular Microscopy Ancillary Study.
PARTICIPANTS: Eighteen patients with graft failure due to endothelial decompensation and 54 individuals matched for most donor and recipient measures at baseline whose grafts did not fail.
MAIN OUTCOME MEASURE: Change in ECD, CV, and HEX values.
RESULTS: Preoperative ECD was not associated with graft failure (P = .43); however, a lower ECD at 6 months was predictive of subsequent failure (P = .004). Coefficient of variation at 6 months was not associated with graft failure in univariate (P = .91) or multivariate (P = .79) analyses. We found a suggestive trend of higher graft failure with lower HEX values at 6 months (P = .02) but not at the established statistical significance (P < .01). The most recent CV or HEX values, as time-dependent variables, were not associated with graft failure (P = .26 and P = .81, respectively). Endothelial cell density values decreased during follow-up, whereas CV and HEX appear to fluctuate without an apparent trend.
CONCLUSIONS AND RELEVANCE: Endothelial cell density at 6 months after penetrating keratoplasty is predictive of graft failure, whereas CV and HEX appear to fluctuate postoperatively, possibly indicating an unstable endothelial population in clear and failing grafts.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006411.
PMID: 23493999 [PubMed - indexed for MEDLINE]
Characterization of novel O-glycans isolated from tear and saliva of ocular rosacea patients.
J Proteome Res. 2013 Mar 1;12(3):1090-100
Authors: Ozcan S, An HJ, Vieira AC, Park GW, Kim JH, Mannis MJ, Lebrilla CB
O-Glycans in saliva and tear isolated from patients suffering from ocular rosacea, a form of inflammatory ocular surface disease, were profiled, and their structures were elucidated using high resolution mass spectrometry. We have previously shown that certain structures, particularly sulfated oligosaccharides, increased in the tear and saliva of rosacea patients. In this study, the structures of these glycans were elucidated using primarily tandem mass spectrometry. There were important similarities in the glycan profiles of tears and saliva with the majority of the structures in common. The structures of the most abundant species common to both tear and saliva, which were also the most abundant species in both, were elucidated. For sulfated species, the positions of the sulfate groups were localized. The majority of the structures were new, with the sulfated glycans comprising mucin core 1- and core 2-type structures. As both saliva and tear are rich in mucins, it is suggested that the O-glycans are mainly components of mucins. The study further illustrates the strong correspondence between the glycans in the tear and saliva of ocular rosacea patients.
PMID: 23294139 [PubMed - indexed for MEDLINE]
Impact of the cornea donor study on acceptance of corneas from older donors.
Cornea. 2012 Dec;31(12):1441-5
Authors: Sugar A, Montoya MM, Beck R, Cowden JW, Dontchev M, Gal RL, Kollman C, Malling J, Mannis MJ, Tennant B, Cornea Donor Study Investigator Group
PURPOSE: To evaluate retrospectively whether the findings from the Cornea Donor Study (CDS) led to changes in the transplantation of corneas from older donors.
METHODS: Eye banks in United States provided complete data on donor age and placement (domestic or international) for 86,273 corneas from 1998 to 2009. The data were analyzed by 3 periods, preceding CDS (1998-1999), during CDS (2000-2007), and after publication of CDS 5-year results (2008-2009), and separately for corneas placed within versus outside the United States.
RESULTS: For corneal tissues transplanted in the United States, the percentage of donors who were 66 years or older increased from 19% before CDS to 21% during CDS and 25% after CDS (P<0.001). Corresponding median (25th-75th percentile) donor ages were 53 (39-63), 54 (41-64), and 57 (46-66), respectively (P<0.001). The opposite trend was observed for corneas distributed outside the United States, with the percentage of donors 66 years and older decreasing from 56% to 42% to 34%, respectively. Donor age trends over time varied by eye bank.
CONCLUSIONS: There was a modest overall increase in the donor age of corneas transplanted in the United States from 1998 to 2009, but the retrospective nature of the study limits our ability to attribute this change to the CDS. The modest increases in the donor age of corneas transplanted is a positive finding, but wider acceptance of older corneal donor tissue should be encouraged based on the 5-year evidence generated by the CDS.
PMID: 22262218 [PubMed - indexed for MEDLINE]
Ocular rosacea--a review.
Arq Bras Oftalmol. 2012 Oct;75(5):363-9
Authors: Vieira AC, Höfling-Lima AL, Mannis MJ
Rosacea is a prevalent chronic cutaneous disorder with variable presentation and severity. Although considered a skin disease, rosacea may evolve the eyes in 58-72% of the patients, causing eyelid and ocular surface inflammation. About one third of the patients develop potentially sight-threatening corneal involvement. Untreated rosacea may cause varying degrees of ocular morbidity. The importance of early diagnosis and adequate treatment cannot be overemphasized. There is not yet a diagnostic test for rosacea. The diagnosis of ocular rosacea relies on observation of clinical features, which can be challenging in up to 90% of patients in whom accompanying roseatic skin changes may be subtle or inexistent. In this review, we describe the pathophysiologic mechanisms proposed in the literature, clinical features, diagnosis and management of ocular rosacea, as well as discuss the need for a diagnostic test for the disease.
PMID: 23471336 [PubMed - indexed for MEDLINE]
Effect of donor and recipient factors on corneal graft rejection.
Cornea. 2012 Oct;31(10):1141-7
Authors: Stulting RD, Sugar A, Beck R, Belin M, Dontchev M, Feder RS, Gal RL, Holland EJ, Kollman C, Mannis MJ, Price F, Stark W, Verdier DD, Cornea Donor Study Investigator Group
PURPOSE: To assess the relationship between donor and recipient factors and corneal allograft rejection in eyes that underwent penetrating keratoplasty in the Cornea Donor Study.
METHODS: Overall, 1090 subjects undergoing corneal transplantation for a moderate risk condition (principally Fuchs dystrophy or pseudophakic corneal edema) were followed for up to 5 years. Associations of baseline recipient and donor factors with the occurrence of a probable or definite rejection event were assessed in univariate and multivariate proportional hazards models.
RESULTS: Eyes with pseudophakic or aphakic corneal edema (n = 369) were more likely to experience a rejection event than eyes with Fuchs dystrophy (n = 676) [34% ± 6% vs. 22% ± 4%; hazard ratio = 1.56; 95% confidence interval (CI), 1.21-2.03]. Among eyes with Fuchs dystrophy, a higher probability of a rejection event was observed in phakic posttransplant eyes compared with those that underwent cataract extraction with or without intraocular lens implantation during penetrating keratoplasty (29% vs. 19%; hazard ratio = 0.54; 95% CI, 0.36-0.82). Female recipients had a higher probability of a rejection event than male recipients (29% vs. 21%; hazard ratio = 1.42; 95% CI, 1.08-1.87) after controlling for the effect of preoperative diagnosis and lens status. Donor age and donor recipient ABO compatibility were not associated with rejection.
CONCLUSIONS: There was a substantially higher graft rejection rate in eyes with pseudophakic or aphakic corneal edema compared to that in eyes with Fuchs dystrophy. Female recipients were more likely to have a rejection event than male recipients. Graft rejection was not associated with donor age.
PMID: 22488114 [PubMed - indexed for MEDLINE]
Glycomic analysis of tear and saliva in ocular rosacea patients: the search for a biomarker.
Ocul Surf. 2012 Jul;10(3):184-92
Authors: Vieira AC, An HJ, Ozcan S, Kim JH, Lebrilla CB, Mannis MJ
The purpose of this study was to study changes in glycosylation in tear and saliva obtained from control and ocular rosacea patients in order to identify potential biomarkers for rosacea. Tear fluid was collected from 51 subjects (28 healthy controls and 23 patients with ocular rosacea). Saliva was collected from 42 of the same subjects (25 controls and 17 patients). Pooled and individual samples were examined to determine overall glycan profiles and individual variations in glycosylation. O-and N- glycans were released from both patients and control subjects. Released glycans were purified and enriched by solid-phase extraction (SPE) with graphitized carbon. Glycans were eluted based on glycan size and polarity. SPE fractions were then analyzed by high-resolution mass spectrometry. Glycan compositions were assigned by accurate masses. Their structures were further elucidated by tandem mass spectrometric using collision-induced dissociation (CID), and specific linkage information was obtained by exoglycosidase digestion. N- and O-glycans were released from 20-μL samples without protein identification, separation, and purification. Approximately 50 N-glycans and 70 O-glycans were globally profiled by mass spectrometry. Most N-glycans were highly fucosylated, while O-glycans were sulfated. Normal tear fluid and saliva contain highly fucosylated glycans. The numbers of sulfated glycans were dramatically increased in tear and saliva of rosacea patients compared to controls. Glycans found in tear and saliva from roseatic patients present highly quantitative similarity. The abundance of highly fucosylated N-glycans in the control samples and sulfated O-glycans in ocular rosacea patient samples may lead to the discovery of an objective diagnostic marker for the disease.
PMID: 22814645 [PubMed - indexed for MEDLINE]
Practice patterns and opinions in the management of recurrent or chronic herpes zoster ophthalmicus.
Cornea. 2012 Jul;31(7):786-90
Authors: Sy A, McLeod SD, Cohen EJ, Margolis TP, Mannis MJ, Lietman TM, Acharya NR
PURPOSE: The objective of this study was to determine current practices and opinions among cornea specialists for treating and preventing recurrences of herpes zoster ophthalmicus (HZO).
METHODS: In November 2010, a survey of 15 questions was distributed to The Cornea Society listserv. Questions identified respondents' treatment practices for recurrent HZO and opinions regarding prolonged antiviral prophylaxis and zoster vaccine.
RESULTS: Of 100 respondents, the majority were cornea specialists (83 of 98, 85%). Eighty-seven percent (84 of 97) reported treating recurrent or chronic cases of HZO in the last year. The most common choice of treatment in the posed recurrent HZO clinical scenario was a combination of oral antiviral and topical corticosteroid (63 of 100, 63%), although significant variability existed in the duration of oral antiviral administration. Fifty-four respondents (56%) believed that prolonged acyclovir prophylaxis could reduce recurrent signs of HZO; 28% (27 of 98) believed that recurrences of HZO could be reduced after the period of acyclovir administration. For patients with a history of HZO, most respondents reported not recommending the adult zoster vaccine (63 of 98, 64%), but 46% (43 of 94) believed that the vaccine could reduce recurrent signs or did not know.
CONCLUSIONS: Many cornea specialists are managing recurrent or chronic cases of HZO, but there is variability in the use of topical corticosteroids and antivirals. Additionally, no consensus exists on the efficacy of prolonged antiviral therapy or the adult zoster vaccine to reduce chronic or recurrent disease. These results demonstrate the need for further systematic study of treatment and prophylaxis for recurrent and chronic HZO.
PMID: 22269677 [PubMed - indexed for MEDLINE]
Jupiter Scleral Lenses: the UC Davis Eye Center experience.
Eye Contact Lens. 2012 May;38(3):179-82
Authors: Pecego M, Barnett M, Mannis MJ, Durbin-Johnson B
PURPOSE: The aim of this study was to evaluate both the indications for and results of fitting the Jupiter Scleral Lens in patients with corneal abnormalities.
METHOD: This was a retrospective case review of 63 patients (107 eyes) fitted with scleral lenses between October 2009 and March 2011 at the UC Davis Eye Center.
RESULTS: Sixty-three percent of 107 eyes were in patients with keratoconus. Other conditions included high postkeratoplasty astigmatism and corneal scarring. The improvement in best-corrected visual acuity compared with previous contact lens or glasses correction was a mean gain of 3.5 Snellen lines (SD=2.6). Seventy-eight percent of patients found the scleral lenses to be comfortable or comfortable. Twenty-five eyes discontinued the wear after at least 3 months.
CONCLUSIONS: Jupiter Scleral lenses are a good alternative for patients with corneal abnormalities and for those who failed other types of lens rehabilitation. Seventy-seven percent of eyes fit with Jupiter Scleral Lenses were still wearing after a follow-up of 3 months.
PMID: 22543730 [PubMed - indexed for MEDLINE]
Contact lenses in the management of keratoconus.
Cornea. 2011 Dec;30(12):1510-6
Authors: Barnett M, Mannis MJ
The range of contact lens modalities currently available for the successful optical correction of keratoconus is greatly expanded. We review lens types currently available for the nonsurgical management of keratoconus, including rigid gas-permeable (GP) lenses, intralimbal lenses, corneoscleral lenses, scleral lenses, hybrid lenses, and piggyback lenses. In this review, we discuss the contemporary range of available lens types and the circumstances in which they are best used.
PMID: 21993461 [PubMed - indexed for MEDLINE]
Practice patterns and opinions in the treatment of acanthamoeba keratitis.
Cornea. 2011 Dec;30(12):1363-8
Authors: Oldenburg CE, Acharya NR, Tu EY, Zegans ME, Mannis MJ, Gaynor BD, Whitcher JP, Lietman TM, Keenan JD
PURPOSE: Management of acanthamoeba keratitis remains challenging for ophthalmologists. We conducted a survey of members of The Cornea Society to elicit expert opinions on the diagnosis and treatment of acanthamoeba keratitis.
METHODS: An online survey was sent to all subscribers of The Cornea Society via the kera-net listserv. Descriptive statistics were performed.
RESULTS: Eighty-two participants completed the online survey. Of the 82 respondents, 76.8% included the combination of clinical examination and culture in their diagnostic strategy and 43.9% used confocal microscopy. Most respondents (97.6%) had used combination therapy with multiple agents to treat acanthamoeba keratitis at some point in the past, whereas a smaller proportion (47.6%) had ever used monotherapy. Respondents most commonly chose polyhexamethylene biguanide as the ideal choice for monotherapy (51.4%), and dual therapy with a biguanide and diamidine as the ideal choice for combination therapy (37.5%). The majority of respondents (62.2%) reported using topical corticosteroids at least some of the time for acanthamoeba keratitis. Keratoplasty was an option considered by most respondents (75.6%), although most (85.5%) would only perform surgery after medical treatment failure.
CONCLUSIONS: There was a wide range of current practice patterns for the diagnosis and treatment of acanthamoeba keratitis. The lack of sufficiently powered comparative effectiveness studies and clinical trials makes evidence-based decision-making for this disease difficult.
PMID: 21993459 [PubMed - indexed for MEDLINE]
Baseline factors related to endothelial cell loss following penetrating keratoplasty.
Arch Ophthalmol. 2011 Sep;129(9):1149-54
Authors: Lass JH, Beck RW, Benetz BA, Dontchev M, Gal RL, Holland EJ, Kollman C, Mannis MJ, Price F, Raber I, Stark W, Stulting RD, Sugar A, Cornea Donor Study Investigator Group
OBJECTIVE: To identify baseline (donor, recipient, and operative) factors that affect endothelial cell loss following penetrating keratoplasty for a moderate-risk condition (principally Fuchs dystrophy or pseudophakic or aphakic corneal edema).
METHODS: In a subset (n = 567) of Cornea Donor Study participants, preoperative and postoperative endothelial cell densities (ECDs) were determined by a central reading center. Multivariate regression analyses were performed to examine which baseline factors correlated with ECD over time.
RESULTS: Larger grafts (P < .001), younger donor age (P < .001), and female donor (P = .004) were significantly associated with higher ECD during follow-up. Median endothelial cell loss at 5 years was 68% for grafts larger than 8.0 to 9.0 mm in diameter, 75% for grafts 7.0 mm to smaller than 8.0 mm in diameter, and 74% for grafts 8.0 mm in diameter. Grafts from female donors experienced a 67% cell loss compared with a 72% cell loss among grafts from male donors. Method of tissue retrieval, donor cause of death, history of diabetes, and time from death to preservation or to surgery were not significantly associated with changes in ECD over time.
CONCLUSIONS: Following penetrating keratoplasty for endothelial dysfunction conditions, larger donor graft size, younger donor age, and female donor were associated with higher ECD over 5 years. These data warrant exploring the possibility that similar associations may exist following endothelial keratoplasty.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006411.
PMID: 21555600 [PubMed - indexed for MEDLINE]
Long-term complications associated with glaucoma drainage devices and Boston keratoprosthesis.
Am J Ophthalmol. 2011 Aug;152(2):209-18
Authors: Li JY, Greiner MA, Brandt JD, Lim MC, Mannis MJ
PURPOSE: To evaluate long-term complications related to glaucoma drainage devices in patients undergoing Boston type 1 keratoprosthesis surgery.
DESIGN: Retrospective case series.
METHODS: All patients who underwent Boston type 1 keratoprosthesis surgery at the University of California, Davis, between 2004 and 2010 were included. Preoperative and postoperative data were reviewed. Twenty-five eyes with glaucoma drainage devices were highlighted. Visual acuity and postoperative complications were tracked at postoperative months 1, 3, 6, 9, and 12 and at annual intervals thereafter.
RESULTS: Forty eyes of 35 patients were evaluated with an average follow-up of 33.6 months. Conjunctival breakdown occurred in association with 10 glaucoma drainage device implants in 9 eyes. Eleven eyes had glaucoma drainage devices placed before keratoprosthesis surgery, 3 eyes underwent glaucoma drainage device placement at the time of surgery, and 2 eyes had a glaucoma drainage device placed after surgery. All but one of the eroded glaucoma drainage devices were placed before surgery. Associated complications included endophthalmitis, hypotony, and keratoprosthesis extrusion, with 6 glaucoma drainage devices requiring removal. Long-term beset-corrected visual acuity was maintained better in eyes in which glaucoma drainage device erosions did not develop.
CONCLUSIONS: One of the main challenges with keratoprosthesis surgery is treating concurrent glaucoma. Glaucoma drainage devices have been advocated as a way to address this long-term complication, but this series suggests that glaucoma drainage device-related complications can cause significant vision loss.
PMID: 21636070 [PubMed - indexed for MEDLINE]
Longer-term vision outcomes and complications with the Boston type 1 keratoprosthesis at the University of California, Davis.
Ophthalmology. 2011 Aug;118(8):1543-50
Authors: Greiner MA, Li JY, Mannis MJ
PURPOSE: To evaluate retention of visual acuity and development of complications after Boston type 1 keratoprosthesis implantation over a longer follow-up period than previously reported.
DESIGN: Cohort study.
PARTICIPANTS: Forty eyes of 35 patients who underwent Boston type 1 keratoprosthesis surgery at the University of California, Davis, between 2004 and 2010.
METHODS: Preoperative, intraoperative, and postoperative parameters were collected and analyzed.
MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) and postoperative complications.
RESULTS: Preoperative visual acuity ranged from 20/150 to light perception and was ≤20/400 in 38 eyes (95%). Preoperative diagnoses included failed corneal transplants (19 eyes, 47.5%), chemical injury (10 eyes, 25%), and aniridia (5 eyes, 12.5%). Mean follow-up duration was 33.6 months (range, 5-72 months). Of 36 eyes followed for ≥1 year, 32 eyes (89%) achieved postoperative BCVA ≥20/200. Of eyes that achieved BCVA ≥20/200, at last follow-up, 19 of 32 eyes (59%) followed for ≥1 year retained BCVA ≥20/200; 16 of 27 eyes (59%) followed for ≥2 years retained BCVA ≥20/200; 7 of 14 eyes (50%) followed for ≥3 years retained BCVA ≥20/200; and 2 of 7 eyes (29%) followed for ≥4 years retained BCVA ≥20/200. End-stage glaucoma most commonly caused vision loss (7 of 13 eyes, 54%) when BCVA ≥20/200 was not retained (follow-up ≥1 year). Glaucoma was newly diagnosed in 11 eyes (27.5%); progression was noted in 9 eyes (22.5%). Glaucoma drainage device erosion occurred in 9 eyes (22.5%). Retroprosthetic membrane formed in 22 eyes (55%), 5 eyes (12.5%) developed endophthalmitis, 6 eyes (15%) developed corneal melt, 7 eyes (17.5%) underwent keratoprosthesis replacement, and 23 eyes (57.5%) required major surgery to treat postoperative complications. The initial keratoprosthesis was retained in 32 eyes (80%).
CONCLUSIONS: Keratoprosthesis implantation remains a viable option for salvaging vision. A significant number of patients lost vision over the postoperative course. Glaucoma and complications related to glaucoma surgery are significant challenges to maintaining good vision after keratoprosthesis surgery. Our study highlights the need for long-term follow-up and a team approach to management, and points to a more guarded long-term visual prognosis after surgery.
FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
PMID: 21397948 [PubMed - indexed for MEDLINE]
Specific ion fluxes generate cornea wound electric currents.
Commun Integr Biol. 2011 Jul;4(4):462-5
Authors: Reid B, Vieira AC, Cao L, Mannis MJ, Schwab IR, Zhao M
The corneal epithelium generates a significant trans-epithelial potential (TEP) which aids in maintaining cornea water balance and transparency. Injury to the cornea causes a short circuit of the TEP at the wound. The TEP in the intact epithelium around the wound acts like a battery, powering significant ion flux and electric current at the wound. These circulating endogenous currents generate an electric field orientated towards the wound, with the wound the cathode. Many cell types, including human corneal epithelial cells and keratinocytes, migrate to the cathode at physiological electric field strengths. Indeed, the electric signal is a powerful stimulator of cell migration, which appears to override other cues such as chemotaxis and wound void. These wound fields also have a dynamic timecourse of change after wounding. It has been assumed that wound electric fields are produced by passive leakage of ions from damaged cells and tissue. Could these fields be actively maintained and regulated as an active wound response? What are the molecular, ionic and cellular mechanisms underlying the wound electric currents?
PMID: 21966572 [PubMed]
Traumatic cataract associated with mini glaucoma shunt.
J Cataract Refract Surg. 2011 Jul;37(7):1360-2
Authors: Li JY, Lim MC, Mannis MJ
We report a case of a 30-year-old woman with aniridia who developed a traumatic cataract related to placement of an Ex-PRESS mini glaucoma shunt. To our knowledge, this potential complication of the device has not been reported.
PMID: 21700114 [PubMed - indexed for MEDLINE]
Retrospective review of graft dislocation rate associated with descemet stripping automated endothelial keratoplasty after primary failed penetrating keratoplasty.
Cornea. 2011 Apr;30(4):414-8
Authors: Clements JL, Bouchard CS, Lee WB, Dunn SP, Mannis MJ, Reidy JJ, John T, Hannush SB, Goins KM, Wagoner MD, Adi MA, Rubenstein JB, Udell IJ, Babiuch AS
PURPOSE: To report the rate of graft dislocation in patients who underwent Descemet stripping automated endothelial keratoplasty (DSAEK) after a previous penetrating keratoplasty (PKP).
METHODS: Institutional review board-approved, multicenter, retrospective chart review. Inclusion criteria included: prior failed PKP and subsequent DSAEK. The primary outcomes measured in this study were the presence of a graft dislocation, rate of rebubble, and graft attachment. Additional variables included: presence of a prior glaucoma drainage device, graft-to-host size disparity, number of sutures remaining in PKP, and stripping of the Descemet membrane at the time of DSAEK surgery.
RESULTS: Ninety patients (97 eyes) were included in the study. In 31% (30 of 97), the endothelial graft dislocated after surgery. All 30 cases required a rebubble except 1, which reattached spontaneously. Ninety-eight percent (95 of 97) of all grafts remained attached for the duration of the follow-up period. Only 2 eyes (2.2%) required repeat graft. Endothelial grafts dislocated in 67% of patients with glaucoma draining devices. The dislocation rate for grafts larger than the host was 12 of 49 (24%), equal to the host was 3 of 17 (18%), and smaller than the host was 8 of 19 (42%). Dislocations occurred in 5 of 21 (24%) of grafts with sutures remaining and 22 of 76 (29%) of those with all sutures out. Five of 12 (42%) cases of grafts performed without stripping the Descemet had dislocations.
CONCLUSIONS: The graft dislocation rate in DSAEK procedures after PKP is comparable to that after primary DSAEK cases. Donor grafts that are smaller than the host PKP and the presence of prior glaucoma drainage devices are risk factors for higher rates of graft dislocation.
PMID: 21099405 [PubMed - indexed for MEDLINE]
Downregulation of PTEN at corneal wound sites accelerates wound healing through increased cell migration.
Invest Ophthalmol Vis Sci. 2011 Apr;52(5):2272-8
Authors: Cao L, Graue-Hernandez EO, Tran V, Reid B, Pu J, Mannis MJ, Zhao M
PURPOSE: The PI3K/Akt pathway is required for cell polarization and migration, whereas the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has inhibitory effects on the PI3K/Akt pathway. The authors therefore hypothesized that wounding would downregulate PTEN and that this downregulation would enhance wound healing.
METHODS: In human corneal epithelial (HCE) cell monolayer and rat cornea scratch wound models, the authors investigated PTEN and Akt expression using Western blot and immunofluorescence analyses. The effects of PTEN and PI3K inhibitors dipotassium bisperoxo (picolinato) oxovanadate (bpv(pic)) and LY294002 on cell migration and wound closure were investigated using time-lapse imaging. Finally, the authors investigated the effect of PTEN inhibition on wound healing in whole rat eyes.
RESULTS: In HCE cell monolayer and rat cornea, PTEN was downregulated at the wound edges within 30 minutes of wounding. The downregulation of PTEN was causal in a simultaneous increase in Akt activation, which was responsible for a significant increase in individual cell migration rate from 8.8 μm/h to 17.3 μm/h. An increased migration rate was maintained for 20 hours. PTEN inhibition significantly enhanced the wound healing rate in the HCE cell monolayer from 10 minutes onward after treatment and reduced the healing time in eye organ culture from 30 to 20 hours.
CONCLUSIONS: Injury to the corneal epithelium downregulates the expression of PTEN at wound edges, allowing increased PI3K/Akt signaling, thereby contributing to a significant enhancement of cell migration and wound healing. These results suggest that PTEN inhibition may be an effective treatment for corneal injury.
PMID: 21212174 [PubMed - indexed for MEDLINE]
Modulating endogenous electric currents in human corneal wounds--a novel approach of bioelectric stimulation without electrodes.
Cornea. 2011 Mar;30(3):338-43
Authors: Reid B, Graue-Hernandez EO, Mannis MJ, Zhao M
PURPOSE: To measure electric current in human corneal wounds and test the feasibility of pharmacologically enhancing the current to promote corneal wound healing.
METHODS: Using a noninvasive vibrating probe, corneal electric current was measured before and after wounding of the epithelium of donated postmortem human corneas. The effects of drug aminophylline and chloride-free solution on wound current were also tested.
RESULTS: Unwounded cornea had small outward currents (0.07 μA/cm²). Wounding increased the current more than 5 fold (0.41 μA/cm²). Monitoring the wound current over time showed that it seemed to be actively regulated and maintained above normal unwounded levels for at least 6 hours. The time course was similar to that previously measured in rat cornea. Drug treatment or chloride-free solution more than doubled the size of wound currents.
CONCLUSIONS: Electric current at human corneal wounds can be significantly increased with aminophylline or chloride-free solution. Because corneal wound current directly correlates with wound healing rate, our results suggest a role for chloride-free and/or aminophylline eyedrops to enhance healing of damaged cornea in patients with reduced wound healing such as the elderly or diabetic patient. This novel approach offers bioelectric stimulation without electrodes and can be readily tested in patients.
PMID: 21099404 [PubMed - indexed for MEDLINE]
[The IC3D classification of the corneal dystrophies].
Klin Monbl Augenheilkd. 2011 Jan;228 Suppl 1:S1-39
Authors: Weiss JS, Møller HU, Lisch W, Kinoshita S, Aldave AJ, Belin MW, Kivelä T, Busin M, Munier FL, Seitz B, Sutphin J, Bredrup C, Mannis MJ, Rapuano C, Van Rij G, Kim EK, Klintworth GK
BACKGROUND: The recent availability of genetic analyses has demonstrated the shortcomings of the current phenotypic method of corneal dystrophy classification. Abnormalities in different genes can cause a single phenotype, whereas different defects in a single gene can cause different phenotypes. Some disorders termed corneal dystrophies do not appear to have a genetic basis.
PURPOSE: The purpose of this study was to develop a new classification system for corneal dystrophies, integrating up-to-date information on phenotypic description, pathologic examination, and genetic analysis.
METHODS: The International Committee for Classification of Corneal Dystrophies (IC3D) was created to devise a current and accurate nomenclature.
RESULTS: This anatomic classification continues to organize dystrophies according to the level chiefly affected. Each dystrophy has a template summarizing genetic, clinical, and pathologic information. A category number from 1 through 4 is assigned, reflecting the level of evidence supporting the existence of a given dystrophy. The most defined dystrophies belong to category 1 (a well-defined corneal dystrophy in which a gene has been mapped and identified and specific mutations are known) and the least defined belong to category 4 (a suspected dystrophy where the clinical and genetic evidence is not yet convincing). The nomenclature may be updated over time as new information regarding the dystrophies becomes available.
CONCLUSIONS: The IC3D Classification of Corneal Dystrophies is a new classification system that incorporates many aspects of the traditional definitions of corneal dystrophies with new genetic, clinical, and pathologic information. Standardized templates provide key information that includes a level of evidence for there being a corneal dystrophy. The system is user-friendly and upgradeable and can be retrieved on the website www.corneasociety.org/ic3d .
PMID: 21290351 [PubMed - indexed for MEDLINE]
Ionic components of electric current at rat corneal wounds.
PLoS One. 2011;6(2):e17411
Authors: Vieira AC, Reid B, Cao L, Mannis MJ, Schwab IR, Zhao M
BACKGROUND: Endogenous electric fields and currents occur naturally at wounds and are a strong signal guiding cell migration into the wound to promote healing. Many cells involved in wound healing respond to small physiological electric fields in vitro. It has long been assumed that wound electric fields are produced by passive ion leakage from damaged tissue. Could these fields be actively maintained and regulated as an active wound response? What are the molecular, ionic and cellular mechanisms underlying the wound electric currents?
METHODOLOGY/PRINCIPAL FINDINGS: Using rat cornea wounds as a model, we measured the dynamic timecourses of individual ion fluxes with ion-selective probes. We also examined chloride channel expression before and after wounding. After wounding, Ca(2+) efflux increased steadily whereas K(+) showed an initial large efflux which rapidly decreased. Surprisingly, Na(+) flux at wounds was inward. A most significant observation was a persistent large influx of Cl(-), which had a time course similar to the net wound electric currents we have measured previously. Fixation of the tissues abolished ion fluxes. Pharmacological agents which stimulate ion transport significantly increased flux of Cl(-), Na(+) and K(+). Injury to the cornea caused significant changes in distribution and expression of Cl(-) channel CLC2.
CONCLUSIONS/SIGNIFICANCE: These data suggest that the outward electric currents occurring naturally at corneal wounds are carried mainly by a large influx of chloride ions, and in part by effluxes of calcium and potassium ions. Ca(2+) and Cl(-) fluxes appear to be mainly actively regulated, while K(+) flux appears to be largely due to leakage. The dynamic changes of electric currents and specific ion fluxes after wounding suggest that electrical signaling is an active response to injury and offers potential novel approaches to modulate wound healing, for example eye-drops targeting ion transport to aid in the challenging management of non-healing corneal ulcers.
PMID: 21364900 [PubMed - indexed for MEDLINE]
Salzmann nodular degeneration.
Cornea. 2010 Mar;29(3):283-9
Authors: Graue-Hernández EO, Mannis MJ, Eliasieh K, Greasby TA, Beckett LA, Bradley JC, Schwab IR
PURPOSE: To describe the characteristic, clinical, and epidemiological features of Salzmann nodular degeneration.
METHODS: Retrospective review of cases. All patients with diagnosis of Salzmann nodular degeneration examined on the Cornea and External Disease Service in the Department of Ophthalmology and Vision Science at the University of California, Davis, were included in this review. Demographic features, clinical characteristics, treatment regimens, surgical procedures, and outcomes were recorded. Descriptive statistics, correlation statistics in bilateral cases, and simple regression models were constructed to assess the effect of potential indicators of severity.
RESULTS: One hundred eighty eyes of 108 patients were included in this review. Seventy-nine patients (72.2%) were female and 29 (27.8%) were male. Seventy-two patients had bilateral disease. The mean age for all patients was 60.8 (13-92) years, and the mean follow-up time was 61.2 months (0-357 months). 76.1% of all eyes were from White. Mean logarithm of the minimum angle of resolution best-corrected visual acuity was 0.24 (Snellen equivalent 20/35, range -0.12 to 2.60, SD 0.44). Decreased visual acuity was the most common symptom in 30.6% of patients. The visual axis was affected in 30% of the cases. Meibomian gland dysfunction was the most common coexistent condition, identified in 41.7% of the cases. For bilateral cases, Spearman correlations for best-corrected visual acuity, magnitude of astigmatism, spherical equivalent, and disease extension were statistically significant (P = 0.001). The number of quadrants affected was found to be a significant predictor for astigmatism (P = 0.01). Surgery was indicated in 41 eyes of 30 patients. Decreased visual acuity was the most common indication for superficial keratectomy. Patients with more than 1 quadrant of the cornea affected or those in which the central visual axis was involved were more likely to require surgery (P = 0.015 and 0.0001, respectively). The surgical outcome was satisfactory in 90.2% of the cases; 9 eyes (21.9%) developed recurrences.
CONCLUSIONS: Salzmann nodular degeneration is a disease of uncertain etiology in which inflammation of the ocular surface may play a role. It predominantly affects women in the sixth decade of life. Management with conservative therapy is generally adequate, and in cases that require surgical intervention, simple nodulectomy is usually effective.
PMID: 20098304 [PubMed - indexed for MEDLINE]
Endothelial cell density to predict endothelial graft failure after penetrating keratoplasty.
Arch Ophthalmol. 2010 Jan;128(1):63-9
Authors: Lass JH, Sugar A, Benetz BA, Beck RW, Dontchev M, Gal RL, Kollman C, Gross R, Heck E, Holland EJ, Mannis MJ, Raber I, Stark W, Stulting RD, Cornea Donor Study Investigator Group
OBJECTIVE: To determine whether preoperative and/or postoperative central endothelial cell density (ECD) and its rate of decline postoperatively are predictive of graft failure caused by endothelial decompensation following penetrating keratoplasty to treat a moderate-risk condition, principally, Fuchs dystrophy or pseudophakic corneal edema.
METHODS: In a subset of Cornea Donor Study participants, a central reading center determined preoperative and postoperative ECD from available specular images for 17 grafts that failed because of endothelial decompensation and 483 grafts that did not fail.
RESULTS: Preoperative ECD was not predictive of graft failure caused by endothelial decompensation (P = .91). However, the 6-month ECD was predictive of subsequent failure (P < .001). Among those that had not failed within the first 6 months, the 5-year cumulative incidence (+/-95% confidence interval) of failure was 13% (+/-12%) for the 33 participants with a 6-month ECD of less than 1700 cells/mm(2) vs 2% (+/-3%) for the 137 participants with a 6-month ECD of 2500 cells/mm(2) or higher. After 5 years' follow-up, 40 of 277 participants (14%) with a clear graft had an ECD below 500 cells/mm(2).
CONCLUSIONS: Preoperative ECD is unrelated to graft failure from endothelial decompensation, whereas there is a strong correlation of ECD at 6 months with graft failure from endothelial decompensation. A graft can remain clear after 5 years even when the ECD is below 500 cells/mm(2).
PMID: 20065219 [PubMed - indexed for MEDLINE]