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.
Why Are Corneal Specialists Resistant to Treating Patients Who Have Severe Ocular Surface Disease With Limbal Stem Cell Deficiency?
Cornea. 2023 Sep 1;42(9):1063-1068. doi: 10.1097/ICO.0000000000003322. Epub 2023 Jun 8.
PURPOSE: To highlight the paucity of surgeons performing ocular surface stem cell transplantation with systemic immunosuppression (OSSTx with SI) for limbal stem cell deficiency (LSCD) patients, suboptimal treatments for LSCD, and obstacles to adoption.
METHODS: A review of the Eye Bank Association of America annual reports and the authors' case volume for OSSTx with SI was performed. Examination of the published literature on corneal surgeries, especially for LSCD, was completed. These findings were combined with our clinical observations to develop this editorial.
RESULTS: Despite techniques and protocols for OSSTx with SI published more than 30 years ago for the treatment of severe bilateral LSCD, only a small number of corneal specialists have adopted these techniques. There is a paucity of attention to this population of patients, with minimal publications to advance this area of our field. We are too often referred patients with LSCD and severe ocular surface disease that have had suboptimal treatments such as penetrating keratoplasties or primary keratoprostheses. Hesitancy for adopting OSSTx with SI is likely due to a lack of exposure to these procedures during training and fear of systemic immunosuppression. Corneal surgeons are likely unaware of the safety of systemic immunosuppression with appropriate monitoring especially when comanaging these patients with an organ transplant specialist.
CONCLUSION: There is a large unmet need for the treatment of corneal blindness secondary to conjunctival and LSCD. For the vast majority of patients, OSSTx should be the first surgical choice to treat these eyes. We hope major ophthalmology centers will meet this need by building programs, and groups of corneal surgeons should collaborate to create regional centers to make this treatment more accessible to help this population.
Preparing the Ocular Surface for a Boston Keratoprosthesis Type 1 Through En Bloc Minor Salivary Gland Transplantation and Mucous Membrane Grafting in End-Stage Stevens-Johnson Syndrome
Cornea. 2023 Jul 1;42(7):912-916. doi: 10.1097/ICO.0000000000003262. Epub 2023 Apr 19.
PURPOSE: This case describes the successful visual restoration of a patient with end-stage Stevens-Johnson syndrome (SJS) with a severely keratinized ocular surface.
METHODS: This study is a case report.
RESULTS: A 67-year-old man with SJS secondary to allopurinol sought visual rehabilitation options. His ocular surface was severely compromised from sequelae of chronic SJS, leaving him with light perception vision bilaterally. The left eye was completely keratinized with severe ankyloblepharon. The right eye had failed penetrating keratoplasty, limbal stem cell deficiency, and a keratinized ocular surface. The patient declined both a Boston type 2 keratoprosthesis and a modified osteo-odonto keratoprosthesis. Therefore, a staged approach was pursued with (1) systemic methotrexate to control ocular surface inflammation, (2) minor salivary gland transplant to increase ocular surface lubrication, (3) lid margin mucous membrane graft to reduce keratinization, and finally, (4) Boston type 1 keratoprosthesis for visual restoration. After minor salivary gland transplant and mucous membrane graft, the Schirmer score improved from 0 mm to 3 mm with improvement in ocular surface keratinization. This approach successfully restored the vision to 20/60, and the patient has retained the keratoprosthesis for over 2 years.
CONCLUSIONS: Sight restoration options are limited in patients with end-stage SJS with a keratinized ocular surface, aqueous and mucin deficiency, corneal opacification, and limbal stem cell deficiency. This case demonstrates successful ocular surface rehabilitation and vision restoration in such a patient through a multifaceted approach that resulted in successful implantation and retention of a Boston type 1 keratoprosthesis.
Vision-Related Quality of Life in Patients With Keratoconus With Enantiomorphic Topography After Bilateral Intrastromal Corneal Ring Implantation
Cornea. 2023 Apr 7. doi: 10.1097/ICO.0000000000003285. Online ahead of print.
PURPOSE: The aim of this study was to evaluate the quality of life (QOL) after intrastromal ring implantation in patients with keratoconus.
METHODS: This was a prospective, randomized, interventional study. We analyzed 60 eyes of 30 patients aged 16 to 35 years who were treated at the Department of Ophthalmology and Visual Sciences, Federal University of São Paulo, Brazil. The Visual Function Questionnaire (VFQ-25) and Short-Form 36 Questionnaire (SF-36) were used before intracorneal ring segment (ICRS) implantation and at 3, 6, and 12 months after surgical intervention.
RESULTS: The mean corrected visual acuity improved from a mean of 0.32 ± 0.2 logMAR (20/40) preoperatively to 0.14 ± 0.11 logMAR (20/25) 1 year postoperatively (P = 0.001). The mean spherical equivalent varied from -7.24 ± 3.47 preoperatively to -4.13 ± 2.41 postoperatively (P = 0.001). The overall composite score for the VFQ-25 improved from 55.1 preoperatively to 80.4 1 postoperatively (P = 0.001). SF-36 showed statistically significant improvement in all scores. When analyzing the correlation between visual acuity and VFQ composite score, a significant correlation was found between both variables (Pearson correlation coefficient of -0.40, P = 0.001).
CONCLUSIONS: Patients with keratoconus had increased psychological symptoms and lower QOL and improved psychosocial criteria associated with corneal remodeling and decreased visual dependence on others after surgery. Extrapolation of these data to the whole keratoconus population suggests that ICRS implantation could improve QOL in these patients.
Interface Fluid Syndrome After Descemet Membrane Endothelial Keratoplasty in Patients With History of Postlaser In Situ Keratomileusis
Cornea. 2023 Jan 23;42(11):1391-4. doi: 10.1097/ICO.0000000000003238. Online ahead of print.
PURPOSE: The aim of this study was to evaluate the visual, pachymetric, tomographic, and biomicroscopic findings in a series of cases presenting laser in situ keratomileusis (LASIK) flap interface fluid syndrome (IFS) after Descemet membrane endothelial keratoplasty (DMEK) surgery.
METHODS: Six cases were included in this study; all patients had a history of LASIK surgery and underwent DMEK for the treatment of bullous keratopathy. After uneventful surgery, all patients presented with corneal edema and IFS under the LASIK flap, which was demonstrated with anterior segment optical coherence tomography (AS-OCT). Visual acuity, clinical findings, pachymetry, endothelial cell count, and AS-OCT were documented during the management of these cases.
RESULTS: IFS appears 2.33 days (±1.03) after DMEK surgery. One case improved with conservative treatment. In 5 cases, the LASIK flap was lifted, the fluid was drained, and the flap was replaced. The mean best-corrected visual acuity after fluid drainage was 0.44 logMAR (range 0.18-1.0) and mean central corneal thickness was 538 μm ± 160. Total resolution of the IFS was achieved at 14.5 days (range 4-30) after DMEK surgery. AS-OCT showed resolution of the flap interface in 5 of 6 cases, while 1 patient required second DMEK due to reaccumulation of the interface fluid.
CONCLUSIONS: IFS can occur after DMEK surgery in patients with previous LASIK surgery. AS-OCT is a valuable tool for monitoring these cases preoperatively and postoperatively. Early surgical management is often needed to achieve resolution.
Corneal Pigment Opacity From Face-Down Positioning After Pars Plana Vitrectomy, Treated With Descemet Stripping Only Technique
Cornea. 2022 Oct 1;41(10):1299-1301. doi: 10.1097/ICO.0000000000002972. Epub 2022 Jan 24.
PURPOSE: The purpose of this study was to report a case of corneal opacity resulting from pigment deposition after face-down positioning, which was treated with Descemet stripping only (DSO) to enable concurrent pars plana vitrectomy (PPV) for retinal detachment repair.
METHODS: A 79-year-old man with a history of Fuchs endothelial dystrophy and retinal detachment presented for the repair of recurrent retinal detachment and evaluation of a central corneal opacity.
RESULTS: The patient was found to have significant corneal endothelial pigment deposition obscuring the view to the fundus. A repeat macula-involving retinal detachment was visualized on limited fundoscopic examination and confirmed using ultrasonography. The patient subsequently underwent combination scleral buckle, DSO, and PPV. DSO achieved corneal clarity for the entire duration of the PPV and allowed for the necessary postoperative face-down positioning. Immunohistochemistry of the corneal specimen revealed deposition of retinal pigment epithelium as the origin of the pigment opacity. The corneal edema cleared at postoperative month 4, and the retina remained attached, resulting in an improvement of visual acuity from counting fingers preoperatively to 20/70.
DISCUSSION: This is, to the best of our knowledge, the first case describing the formation of a corneal endothelial opacity because of retinal pigment epithelium deposition associated with face-down positioning after PPV for retinal detachment. DSO is a minimally invasive, viable alternative to endothelial keratoplasty or temporary keratoprosthesis placement for the clearance of focal corneal endothelial opacities for PPV.
Animal models of corneal endothelial dysfunction to facilitate development of novel therapies
Ann Transl Med. 2021 Aug;9(15):1271. doi: 10.21037/atm-20-4389.
Progressive corneal endothelial disease eventually leads to corneal edema and vision loss due to the limited regenerative capacity of the corneal endothelium in vivo and is a major indication for corneal transplantation. Despite the relatively high success rate of corneal transplantation, there remains a pressing global clinical need to identify improved therapeutic strategies to address this debilitating condition. To evaluate the safety and efficacy of novel therapeutics, there is a growing demand for pre-clinical animal models of corneal endothelial dysfunction. In this review, experimentally induced, spontaneously occurring and genetically modified animal models of corneal endothelial dysfunction are described to assist researchers in making informed decisions regarding the selection of the most appropriate animal models to meet their research goals.
Current Global Bioethical Dilemmas in Corneal Transplantation
Cornea. 2020 Apr;39(4):529-533. doi: 10.1097/ICO.0000000000002246.
PURPOSE: To analyze some of the bioethical dilemmas that may arise during the process required for corneal transplantation.
METHODS: We conducted a narrative review based on the available literature and the experience of cornea specialists from 3 different countries.
RESULTS: Bioethical dilemmas related to informed consent for organ and tissue donation, allocation of corneal tissues, transplant tourism, corneal tissue exportation and importation, and for-profit eye banking were analyzed and discussed.
CONCLUSIONS: Around the world, the number of required corneal transplants exceeds the number of donated corneas that are available and suitable for transplantation. This shortage of corneal tissue has led to the emergence of practices that may put the 4 basic principles of bioethics at risk: autonomy, beneficence, nonmaleficence, and justice. Therefore, it has been necessary to create ethical guidelines such as the Barcelona Principles and the World Health Organization Principles of Transplantation that attempt to regulate these practices.
The Use of Electrotherapeutics in Ophthalmology
Am J Ophthalmol. 2020 Mar;211:4-14. doi: 10.1016/j.ajo.2019.11.011. Epub 2019 Nov 15.
PURPOSE: To present a perspective on the use of electrotherapeutics in the history of ophthalmology along with the development of novel contemporary ophthalmic instrumentation.
DESIGN: Perspective study.
METHODS: We reviewed historical journals, articles, and books discussing the use of electricity and electrotherapeutics in ophthalmology.
RESULTS: Electrotherapeutic applications have been researched and used to treat ocular diseases as far back as the 18th century. By the 20th century, research in electrotherapeutics in ophthalmology had caught the eye of Edward Jackson, the first president of the American Academy of Ophthalmology and Otolaryngology and first editor of the present (third) series American Journal of Ophthalmology. Edward Jackson published an extensive review on this topic and reported a variety of modalities used to treat ocular diseases.
CONCLUSIONS: While many early therapeutic uses of electricity did not produce effective and replicable results, studies on electrical stimulation of the eye provided the foundation for the development of clinically significant vision enhancing and restoring instrumentation.
Practice Patterns in the Management of Primary Pterygium: A Survey Study
Cornea. 2019 Nov;38(11):1339-1344. doi: 10.1097/ICO.0000000000002091.
PURPOSE: To characterize cornea specialists' current practice preferences in the management of primary pterygium.
METHODS: A 25-item survey regarding indications for surgery, surgical technique, use of adjuvant therapy, type and duration of postoperative therapy, and treatment of early recurrences was designed and sent to members of the Cornea Society through the kera-net listserv.
RESULTS: In total, 199 cornea specialists completed the questionnaire. More than 90% considered that surgery should be performed when there is proximity of the pterygium to the visual axis, pain or redness, eye movement restriction, or induction of astigmatism. Cosmesis was considered as an indication by 41.7% of the participants. The most frequent technique for pterygium excision was complete resection including the base and a moderate quantity of Tenon capsule followed by autologous conjunctival or limbal-conjunctival graft. The preferred graft fixation method in this survey was fibrin glue (61.2%). Most respondents reported a recurrence rate of less than 5% and no use of adjuvant agents to prevent recurrence. When early recurrence did occur, the preferred agents were corticosteroids.
CONCLUSIONS: This study reflects the preferences of cornea experts regarding primary pterygium treatment and may serve as a guide for the management of this pathology.
Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel
Br J Dermatol. 2020 May;182(5):1269-1276. doi: 10.1111/bjd.18420. Epub 2019 Oct 16.
BACKGROUND: A transition from a subtyping to a phenotyping approach in rosacea is underway, allowing individual patient management according to presenting features instead of categorization by predefined subtypes. The ROSacea COnsensus (ROSCO) 2017 recommendations further support this transition and align with guidance from other working groups.
OBJECTIVES: To update and extend previous global ROSCO recommendations in line with the latest research and continue supporting uptake of the phenotype approach in rosacea through clinical tool development.
METHODS: Nineteen dermatologists and two ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and management. Voting was electronic and blinded.
RESULTS: Delphi statements on which the panel achieved consensus of ≥ 75% voting 'Agree' or 'Strongly agree' are presented. The panel recommends discussing disease burden with patients during consultations, using four questions to assist conversations. The primary treatment objective should be achievement of complete clearance, owing to previously established clinical benefits for patients. Cutaneous and ocular features are defined. Treatments have been reassessed in line with recent evidence and the prior treatment algorithm updated. Combination therapy is recommended to benefit patients with multiple features. Ongoing monitoring and dialogue should take place between physician and patients, covering defined factors to maximize outcomes. A prototype clinical tool (Rosacea Tracker) and patient case studies have been developed from consensus statements.
CONCLUSIONS: The current survey updates previous recommendations as a basis for local guideline development and provides clinical tools to facilitate a phenotype approach in practice and improve rosacea patient management. What's already known about this topic? A transition to a phenotype approach in rosacea is underway and is being recommended by multiple working groups. New research has become available since the previous ROSCO consensus, necessitating an update and extension of recommendations. What does this study add? We offer updated global recommendations for clinical practice that account for recent research, to continue supporting the transition to a phenotype approach in rosacea. We present prototype clinical tools to facilitate use of the phenotype approach in practice and improve management of patients with rosacea.
Epithelial downgrowth after femtosecond laser-assisted cataract surgery
Am J Ophthalmol Case Rep. 2019 Jul 2;15:100507. doi: 10.1016/j.ajoc.2019.100507. eCollection 2019 Sep.
PURPOSE: To present the case of a 72-year-old female with epithelial downgrowth after femtosecond laser-assisted cataract surgery.
OBSERVATIONS: The patient previously underwent YAG vitreolysis after uncomplicated femtosecond laser-assisted cataract surgery and presented 1 year later with epithelial downgrowth causing complete pupillary block and severe angle closure glaucoma. Subsequent management with nd:YAG peripheral iridotomies failed rapidly leading to a confusing presentation with a flat anterior chamber and high intraocular pressure ultimately requiring surgical management.
CONCLUSIONS: We describe the occurrence of epithelial downgrowth after femtosecond laser-assisted cataract surgery and illustrate the utility of ultrasound biomicroscopy to differentiate between severe pupillary block and malignant glaucoma.
Posterior Segment Complications and Impact on Long-Term Visual Outcomes in Eyes With a Type 1 Boston Keratoprosthesis
Cornea. 2019 Sep;38(9):1111-1116. doi: 10.1097/ICO.0000000000001983.
PURPOSE: To determine the spectrum of retinal complications (RCs) in a cohort of eyes with a type 1 Boston keratoprosthesis (KPro).
METHODS: All patients (36 eyes of 31 patients) who received a type 1 Boston KPro from January 2004 to December 2015 at the University of California, Davis, were included. Electronic medical records were reviewed for relevant clinical data. Demographic information, initial corneal diagnosis, postoperative course, posterior segment complications, preoperative and final visual acuity were tabulated and analyzed.
RESULTS: Posterior segment complications after type 1 Boston KPro were identified in 56% of eyes (n = 20). They included retinal detachment (n = 11; 31%), retroprosthetic membrane (n = 10; 28%), endophthalmitis (n = 7; 19%), cystoid macular edema (n = 5; 14%), epiretinal membrane (n = 4; 11%), vitreous hemorrhage (n = 2; 6%), choroidal detachment (n = 2; 6%), retinal vein occlusion (n = 1; 3%), and macular hole (n = 1; 3%). During the average follow-up period of 53.8 months (median, 57.1 months; range, 1.8-108.7 months) after type 1 Boston KPro, final best-corrected visual acuity improved by a mean of 0.12 logarithm of the minimum angle of resolution (LogMAR) units (range, -2.26 to +2.26) overall. The proportion of eyes with final best-corrected visual acuity better than 20/200 was 2 of 20 (10%) in the group with RCs, in contrast to 7 of 16 eyes (44%) noted among eyes without RCs.
CONCLUSIONS: Long-term visual outcomes in eyes after type 1 Boston KPro may depend, in part, on maintaining a healthy posterior pole. Retinal detachment, in particular, may represent a threat to ultimate visual functioning. Regular examination of the peripheral fundus is recommended.
Effectiveness of Intrastromal Corneal Ring Implantation in the Treatment of Adult Patients With Keratoconus: A Systematic Review
J Refract Surg. 2019 Mar 1;35(3):191-200. doi: 10.3928/1081597X-20190109-02.
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.].
Whorl pattern keratopathies in veterinary and human patients
Vet Ophthalmol. 2018 Nov;21(6):661-667. doi: 10.1111/vop.12552. Epub 2018 Feb 6.
The course travelled by corneal epithelial cells from their stem cell niche at the limbus toward the vertex of the cornea is normally not evident due to their transparency, but in certain conditions, the epithelial cells can be rendered visible to the clinician. In such cases, the pathway taken by epithelial cells can manifest as a whorl pattern described using a variety of terms including hurricane keratitis/keratopathy, vortex keratopathy, whorl keratopathy, cornea verticillata, and at times, named after causative agents as exemplified by amiodarone keratopathy. Here, we briefly discuss the terminology used and the spectrum of conditions that can result in keratopathies with whorl patterns in human patients. We review the manifestations of such patterns in veterinary patients and discuss the state of understanding of the underlying forces that create the whorl distribution of epithelial cells on the ocular surface.
Keratoconus and Personality-A Review
Cornea. 2018 Mar;37(3):400-404. doi: 10.1097/ICO.0000000000001479.
PURPOSE: To assess the existing literature on the subject of keratoconus and personality and to propose a theory that might account for the perceived personality changes associated with this condition.
METHODS: A literature search was conducted in the PubMed database using the term "keratoconus" in combination with keywords such as personality, psychiatry, psychology, anxiety, depression, or psychosis. A total of 15 articles pertaining to personality and psychiatric disorders in keratoconus were retained and reviewed.
RESULTS: Although patients with keratoconus tend to score differently on personality scales compared with normal controls, the literature fails to substantiate the existence of a unique "keratoconic personality." Instead, patients with keratoconus prove to have more dysfunctional coping mechanisms that specifically alter their interaction with health care providers and may account for the persistent clinical impression of less respectful, conforming, and cooperative patients.
CONCLUSIONS: We hypothesize that the stage of life at which keratoconus commonly presents plays a crucial role in personality and coping mechanism development that significantly affects behavioral patterns and the relationship with caregivers.
Favorable Outcome in Coccidioides Endophthalmitis-A Combined Medical and Surgical Treatment Approach
Cornea. 2017 Nov;36(11):1423-1425. doi: 10.1097/ICO.0000000000001353.
PURPOSE: To describe a case of Coccidioides endophthalmitis that resulted in a favorable visual outcome after a combined medical and surgical approach.
METHODS: A 33-year-old previously healthy woman was referred for evaluation of dyspnea and left-sided vision loss, which began 3 months before, after a trip to Nevada. She was found to have a pulmonary cavitary lesion and fluffy white material in the anterior chamber. An aqueous and vitreous paracentesis grew Coccidioides species. She was managed medically with a total of 7 weekly intravitreal injections of amphotericin B and intravenous liposomal amphotericin B followed by transition to oral posaconazole. Seven months after presentation, to ensure ocular sterilization and to clear the visual axis, she underwent temporary keratoprosthesis implantation, anterior segment reconstruction, removal of a cyclitic membrane and the crystalline lens, pars plana vitrectomy, placement of a pars plana Ahmed drainage device, and penetrating keratoplasty.
RESULTS: After surgical intervention and with maintenance posaconazole therapy, the patient had resolution of her dyspnea and improved uncorrected (aphakic) vision with a clear corneal graft, quiet anterior chamber, and normal optic nerve and retina.
CONCLUSIONS: A combined medical and surgical approach resulted in a favorable visual outcome and avoided the need for enucleation.
Evaluation of a Portable Artificial Vision Device Among Patients With Low Vision
JAMA Ophthalmol. 2016 Jul 1;134(7):748-52. doi: 10.1001/jamaophthalmol.2016.1000.
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.
In vivo evaluation of the cornea and conjunctiva of the normal laboratory beagle using time‐and Fourier‐domain optical coherence tomography and ultrasound pachymetry
Veterinary ophthalmology, 19(1), pp.50-56
Ocular Adverse Events Associated with Antibody-Drug Conjugates in Human Clinical Trials
J Ocul Pharmacol Ther. 2015 Dec;31(10):589-604. doi: 10.1089/jop.2015.0064. Epub 2015 Nov 5.
This article reviews ocular adverse events (AEs) reported in association with administration of antibody-drug conjugates (ADCs) in human clinical trials. References reporting ocular toxicity or AEs associated with ADCs were collected using online publication searches. Articles, abstracts, or citations were included if they cited ocular toxicities or vision-impairing AEs with a confirmed or suspected association with ADC administration. Twenty-two references were found citing ocular or vision-impairing AEs in association with ADC administration. All references reported use of ADCs in human clinical trials for treatment of various malignancies. The molecular target and cytotoxic agent varied depending on the ADC used. Ocular AEs affected a diversity of ocular tissues. The most commonly reported AEs involved the ocular surface and included blurred vision, dry eye, and corneal abnormalities (including microcystic corneal disease). Most ocular AEs were not severe (≤ grade 2) or dose limiting. Clinical outcomes were not consistently reported, but when specified, most AEs improved or resolved with cessation of treatment or with ameliorative therapy. A diverse range of ocular AEs are reported in association with administration of ADCs for the treatment of cancer. The toxicologic mechanism(s) and pathogenesis of such events are not well understood, but most are mild in severity and reversible. Drug development and medical professionals should be aware of the clinical features of these events to facilitate early recognition and intervention in the assessment of preclinical development programs and in human clinical trials.
Single-Pass Microkeratome System for Eye Bank DSAEK Tissue Preparation: Is Stromal Bed Thickness Predictable and Reproducible?
Cornea. 2016 Jan;35(1):95-9. doi: 10.1097/ICO.0000000000000675.
PURPOSE: To evaluate the predictability and reproducibility of stromal bed thickness for single-pass donor Descemet stripping automated endothelial keratoplasty (DSAEK) tissue preparation, using the ML7 Microkeratome Donor Cornea System (Med-logics Inc, Athens, TX).
METHODS: In this retrospective chart review of 256 consecutive corneal tissue preparations for DSAEK surgery, from June 2013 to August 2014, tissue thicknesses were divided into 3 groups, depending on surgeon preference: <91 μm (group A), 90 to 120 μm (group B), and 120 to 160 μm (group C). Precut and postcut data were recorded.
RESULTS: Average postcut donor corneal thickness was 114 ± 30 μm (range 60-183 μm), whereas the average in group A was 97 ± 23 μm (range 60-128), in group B was 113 ± 21 μm (range 77-179), and in group C was 134 ± 43 (range 89-183). Average postcut endothelial cell density was very adequate at 3013 ± 250 cells per square millimeter. There were a total of 7 failed procedures from 256 attempts, which represents a rate of 2.7%. This rate decreases to 1.5% when analyzing the last 200 cuts.
CONCLUSIONS: The ML7 Microkeratome Donor Cornea System allows for reliable and reproducible DSAEK tissue preparation. Ultrathin DSAEK tissues can be prepared with a single-pass. Aiming for a graft thickness between 90 and 120 μm seems to be most reliable.
Use of Scleral Lenses and Miniscleral Lenses After Penetrating Keratoplasty
Eye Contact Lens. 2016 May;42(3):185-9. doi: 10.1097/ICL.0000000000000163.
PURPOSE: To examine the clinical outcomes of scleral lenses for visual rehabilitation after penetrating keratoplasty (PK).
METHODS: A retrospective review was conducted for 34 patients (48 eyes) who had a history of prior PK and were fit with scleral lenses between October 2009 and December 2013 at the UC Davis Eye Center.
RESULTS: The most common initial indication for PK was keratoconus in 27 eyes (56%). Thirty-three eyes (69%) had previously been fit with other types of contact lenses, with small-diameter rigid gas-permeable lenses being the most common. The improvement in best-corrected visual acuity with a scleral lens compared with prior spectacle refraction or other contact lens was a mean of two best-corrected visual acuity lines. Forty-four eyes (91.7%) achieved functional vision with best scleral lens-corrected visual acuities of 20/40 or better. Patients who continued wearing scleral lenses were significantly more likely to report "good" subjective vision compared with patients who abandoned scleral lens wear (P=0.009), although change in objective best-corrected visual acuity did not differ significantly. There were no cases of infectious keratitis. Six eyes (12.5%) developed graft rejection; 3 were able to resume scleral lens wear. Nineteen eyes (39.5%) discontinued scleral lens wear for various reasons, the most common reason for discontinuation of lens wear was difficulty with scleral lens insertion or removal (8 eyes, 42.1%).
CONCLUSION: Scleral lenses are effective and safe in patients who have had PK. There was a mean gain in visual acuity, with the majority of patients achieving 20/40 vision or better. The patient's subjective perception of vision was a significant factor in determining whether scleral lens wear was continued or abandoned.
<em>In vivo</em> volumetric depth-resolved vasculature imaging of human limbus and sclera with 1<em>μ</em>m swept source phase-variance optical coherence angiography
J Opt. 2015 Jun;17(6):065301. doi: 10.1088/2040-8978/17/6/065301.
We present nnnnnin vivo volumetric depth-resolved vasculature images of the anterior segment of the human eye acquired with phase-variance based motion contrast using a high-speed (100 kHz, 105 A-scans/s) swept source optical coherence tomography system (SSOCT). High phase stability SSOCT imaging was achieved by using a computationally efficient phase stabilization approach. The human corneo-scleral junction and sclera were imaged with swept source phase-variance optical coherence angiography and compared with slit lamp images from the same eyes of normal subjects. Different features of the rich vascular system in the conjunctiva and episclera were visualized and described. This system can be used as a potential tool for ophthalmological research to determine changes in the outflow system, which may be helpful for identification of abnormalities that lead to glaucoma.
In vivo ocular imaging of the cornea of the normal female laboratory beagle using confocal microscopy
Vet Ophthalmol. 2016 Jan;19(1):63-7. doi: 10.1111/vop.12264. Epub 2015 Mar 6.
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.
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. 2016 Jan;19(1):50-6. doi: 10.1111/vop.12256. Epub 2015 Feb 10.
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.
Factors associated with corneal graft survival in the cornea donor study
JAMA Ophthalmol. 2015 Mar;133(3):246-54. doi: 10.1001/jamaophthalmol.2014.3923.
IMPORTANCE: The Cornea Donor Study (CDS) showed that donor age is not a factor in survival of most penetrating keratoplasties for endothelial disease. Secondary analyses confirm the importance of surgical indication and presence of glaucoma in outcomes at 10 years.
OBJECTIVE: To assess the relationship between donor and recipient factors and corneal graft survival in the CDS.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter prospective, double-masked, controlled clinical trial conducted at 80 clinical sites. One hundred five surgeons enrolled 1090 participants undergoing corneal transplant for a moderate-risk condition, principally Fuchs dystrophy or pseudophakic or aphakic corneal edema (PACE). Forty-three eye banks provided corneas.
INTERVENTIONS: Corneas from donors younger than 66 years and donors 66 years or older were assigned, masked to donor age. Surgery and postoperative care were performed according to the surgeons' usual routines. Participants were followed up for as long as 12 years.
MAIN OUTCOMES AND MEASURES: Graft failure, defined as a regrafting procedure or a cloudy cornea for 3 consecutive months.
RESULTS: The 10-year cumulative probability of graft failure was higher in participants with PACE than in those with Fuchs dystrophy (37% vs 20%; hazard ratio [HR], 2.1 [99% CI, 1.4-3.0]; P < .001) and in participants with a history of glaucoma before penetrating keratoplasty, particularly with prior glaucoma surgery (58% with prior glaucoma surgery and use of medications to lower intraocular pressure at the time of surgery vs 22% with no history of glaucoma surgery or medication use; HR, 4.1 [99% CI, 2.2-7.5]; P < .001). We found trends toward increased graft failure in recipients who were 70 years or older compared with those younger than 60 years (29% vs 19%; HR, 1.2 [99% CI, 0.7-2.1]; P = .04) or were African American (HR, 1.5; P = .11) or who had a history of smoking (35% vs 24%; HR, 1.6 [99% CI, 0.9-2.8]; P = .02). Lower endothelial cell density (ECD) and higher corneal thickness (CT) at 6 months (6% vs 41% for ECD ≥2700 vs <1700 cells/mm2 [P < .001]; 14% vs 36% for CT <500 vs ≥600 μm [P = .001]), 1 year (4% vs 39% for ECD ≥2700 vs <1700 cells/mm2 [P < .001]; 18% vs 28% for CT <500 vs ≥600 μm [P = .04]), and 5 years (2% vs 29% for ECD ≥1500 vs <500 cells/mm2 [P < .001]; 7% vs 34% for CT <550 vs ≥650 μm [P < .001]) were associated with subsequent graft failure.
CONCLUSIONS AND RELEVANCE: Most penetrating corneal grafts for Fuchs dystrophy or PACE remain clear at 10 years. The risk for failure is greater for graft recipients with PACE and those with a history of glaucoma. Measurements of ECD and CT during the course of postkeratoplasty follow-up are associated with a risk for failure. However, even with very low ECD and high CT at 5 years, most corneas remain clear at 10 years.
Corneal graft rejection 10 years after penetrating keratoplasty in the cornea donor study
Cornea. 2014 Oct;33(10):1003-9. doi: 10.1097/ICO.0000000000000212.
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.
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. doi: 10.1097/ICO.0000000000000160.
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.
Interfacial phenomena and the ocular surface
Ocul Surf. 2014 Jul;12(3):178-201. doi: 10.1016/j.jtos.2014.01.004. Epub 2014 Apr 16.
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.
Simultaneous surgery for corneal edema and aphakia: DSEK and placement of a retropupillary iris claw lens
Cornea. 2014 Feb;33(2):197-200. doi: 10.1097/ICO.0b013e3182a9dffb.
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.
Donor age and factors related to endothelial cell loss 10 years after penetrating keratoplasty: Specular Microscopy Ancillary Study
Ophthalmology. 2013 Dec;120(12):2428-2435. doi: 10.1016/j.ophtha.2013.08.044.
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.
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):2419-2427. doi: 10.1016/j.ophtha.2013.08.026.
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.
Ocular rosacea: common and commonly missed
J Am Acad Dermatol. 2013 Dec;69(6 Suppl 1):S36-41. doi: 10.1016/j.jaad.2013.04.042.
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.
Evaluation of microbial flora in eyes with a Boston type 1 Keratoprosthesis
Cornea. 2013 Dec;32(12):1537-9. doi: 10.1097/ICO.0b013e3182a81992.
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.
Epithelial downgrowth after penetrating keratoplasty: imaging by high-resolution optical coherence tomography and in vivo confocal microscopy
Cornea. 2013 Nov;32(11):1505-8. doi: 10.1097/ICO.0b013e31829c6d13.
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.
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. doi: 10.1117/1.JBO.18.8.086002.
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.
Eye banking and corneal transplantation communicable adverse incidents: current status and project NOTIFY
Cornea. 2013 Aug;32(8):1155-66. doi: 10.1097/ICO.0b013e31828f9d64.
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.
High-resolution spectral domain anterior segment optical coherence tomography in type 1 Boston keratoprosthesis
Cornea. 2013 Jul;32(7):951-5. doi: 10.1097/ICO.0b013e318285c8f4.
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.
Standard terminology and labeling of ocular tissue for transplantation
Cornea. 2013 Jun;32(6):725-8. doi: 10.1097/ICO.0b013e3182873405.
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.
Anterior segment OCT and confocal microscopy findings in atypical corneal intraepithelial neoplasia
Cornea. 2013 Jun;32(6):875-9. doi: 10.1097/ICO.0b013e318285cab9.
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.
Endothelial morphometric measures to predict endothelial graft failure after penetrating keratoplasty
JAMA Ophthalmol. 2013 May;131(5):601-608. doi: 10.1001/jamaophthalmol.2013.1693.
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.
Ocular rosacea--a review
Arq Bras Oftalmol. 2012 Oct;75(5):363-9. doi: 10.1590/s0004-27492012000500016.
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.
Corneal thickness as a predictor of corneal transplant outcome
Cornea. 2013 Jun;32(6):729-36. doi: 10.1097/ICO.0b013e31827b14c7.
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.
Characterization of novel O-glycans isolated from tear and saliva of ocular rosacea patients
J Proteome Res. 2013 Mar 1;12(3):1090-100. doi: 10.1021/pr3008013. Epub 2013 Feb 6.
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.
Intereye asymmetry detected by Scheimpflug imaging in subjects with normal corneas and keratoconus
Cornea. 2013 Jun;32(6):779-82. doi: 10.1097/ICO.0b013e31827b14ae.
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.
Glycomic analysis of tear and saliva in ocular rosacea patients: the search for a biomarker
Ocul Surf. 2012 Jul;10(3):184-92. doi: 10.1016/j.jtos.2012.04.003. Epub 2012 May 3.
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.
Jupiter Scleral Lenses: the UC Davis Eye Center experience
Eye Contact Lens. 2012 May;38(3):179-82. doi: 10.1097/ICL.0b013e31824daa5e.
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.