Feeder-free differentiation of cells exhibiting characteristics of corneal endothelium from human induced pluripotent stem cells.

The purpose of this study was to devise a strategy for the derivation of corneal endothelial cells (CEnCs) from adult fibroblast-derived induced pluripotent stem cells (iPSCs). IPSCs were generated from an adult human with normal ocular history via expression of OCT4, SOX2, KLF4 and c-MYC Neural crest cells (NCCs) were differentiated from iPSCs via addition of CHIR99021 and SB4315542. NCCs were driven toward a CEnC fate via addition of B27, PDGF-BB and DKK-2 to CEnC media. Differentiation of NCCs and CEnCs was evaluated via rt-PCR, morphological and immunocytochemical analysis. At 17 days post-NCC induction, there were notable changes in cell morphology and upregulation of the neural crest lineage transcripts PAX3, SOX9, TFAP2A, SOX10 and p75NTR and the proteins p75/NGFR and SOX10. Exposure of NCCs to B27, PDGF-BB and DKK-2 induced a shift in morphology from a spindle-shaped neural phenotype to a tightly-packed hexagonal appearance and increased expression of the transcripts ATP1A1, COL8A1, COL8A2, AQP1 and CDH2 and the proteins ZO-1, N-Cad, AQP-1 and Na+/K+ATPase. Replacement of NCC media with CEnC media on day 3, 5 or 8 reduced the differentiation time needed to yield CEnCs. IPSC-derived CEnCs could be used for evaluation of cornea endothelial disease pathophysiology and for testing of novel therapeutics.

Glaucoma-associated corneal endothelial cell damage: A review.

The corneal endothelium is critical in maintaining a healthy and clear cornea. Corneal endothelial cells have a significant reserve function, but preservation of these cells is paramount as they have limited regenerative capacity. Glaucoma is a prevalent disease, and damage to the corneal endothelium may be caused by the disease process itself as well as by its treatment. The mechanisms involved in glaucoma-associated damage to the corneal endothelium need further investigation. Understanding how glaucoma and glaucoma surgery impact the endothelium is important for protecting corneal clarity and visual acuity in all glaucoma patients, including those undergoing corneal transplant. We will discuss a range of identified factors that may impact corneal endothelial cell health in glaucoma, including intraocular pressure, glaucoma medications, surgical glaucoma management, mechanical forces, and alterations in the aqueous environment.

Incidence and Outcomes of Positive Donor Corneoscleral Rim Fungal Cultures after Keratoplasty.

PURPOSE: To determine the incidence of positive corneoscleral donor rim fungal cultures after keratoplasty and to report clinical outcomes of grafts with culture-positive donor rims. DESIGN: Retrospective cohort study. PARTICIPANTS: Consecutive donor corneas and keratoplasty recipients at a single tertiary referral center over 20 years. METHODS: Patient charts were reviewed to determine the incidence of positive donor rim fungal cultures and clinical outcomes of all grafts using contaminated tissue. MAIN OUTCOME MEASURES: The primary outcome measures were positive donor rim fungal culture results and the development of postkeratoplasty fungal infection using corresponding corneal tissue. The secondary outcome measure was the impact of postoperative prophylaxis on donor tissue-associated infections. RESULTS: A total of 3414 keratoplasty cases were included in the statistical analysis. Seventy-one cases (2.1%) were associated with a fungal culture-positive donor rim. Candida species were cultured in 40 cases (56.3%). There was a higher incidence of positive rim cultures over the last 5 years of the analytic period compared with the first 15 years (P = 0.018). Fungal keratitis developed in 4 cases (5.6%), and all patients required further surgical intervention to achieve cure. There were no cases of fungal endophthalmitis. Empiric antimycotic prophylaxis initiated at the time of positive culture result reduced the incidence of keratitis from 15.8% in untreated cases to 1.9% in treated cases (P = 0.056). CONCLUSIONS: Positive donor rim fungal cultures are uncommon, but carry an unacceptably high risk of postoperative fungal infection. This risk may be reduced with prophylactic antimycotic therapy when culture-positive donor rims are identified.

Boston Type 1 Keratoprosthesis: Visual Outcomes, Device Retention, and Complications.

PURPOSE: To determine the visual outcomes, device retention, and complications after Boston type 1 keratoprosthesis (KPro-1) device implantation. METHODS: Comprehensive review of every case of KPro-1 implantation at a tertiary eye care center. RESULTS: The initial KPro-1 procedure, performed in 75 eyes without a previous keratoprosthesis, was included in the analysis. During the first 6 postoperative months, improvement occurred in the mean preoperative best-corrected visual acuity of 20/1265 to a mean best-obtained postoperative visual acuity of 20/97 (P < 0.001). After a mean follow-up period of 41.4 months (range, 0.8-82.8 months), the final mean best-corrected visual acuity was 20/428. Improved vision was recorded in 43 eyes (57.3%), ambulatory vision (≥20/400) in 47 eyes (62.7%), intermediate functional vision (≥20/80) in 23 eyes (30.7%), and full functional vision (≥20/40) in 11 eyes (14.7%). The initial device was retained in 64 eyes (85.3%), with a Kaplan-Meier retention probability of 96% at 6 months and 82% at 5 years. One or more sight-threatening complications occurred in 51 eyes (68%). These included device extrusion in 11 eyes (14.7%), ulcerative keratitis in 12 eyes (16%), endophthalmitis in 7 eyes (9.3%), sterile vitritis in 3 eyes (4%), retroprosthetic membranes in 25 eyes (33.3%), maculopathy in 26 eyes (34.7%), retinal detachment in 9 eyes (12%), and progressive optic neuropathy in 7 eyes (9.3%). CONCLUSIONS: Boston KPro-1 implantation is associated with satisfactory visual outcomes and excellent device retention in a majority of cases. However, serious postoperative complications are common and may compromise the final visual result.

Incidence of Cystoid Macular Edema After Descemet Membrane Endothelial Keratoplasty as a Staged and Solitary Procedure.

PURPOSE: To compare the incidence of visually significant postoperative cystoid macular edema (CME) in pseudophakic eyes after Descemet membrane endothelial keratoplasty (DMEK) performed after recent versus remote cataract surgery. METHODS: A retrospective chart review was performed of all consecutive eyes that underwent DMEK without concurrent cataract surgery at the University of Iowa between October 2012 and December 2014. The DMEK procedures were classified as staged if performed between 2 weeks and 6 months after cataract surgery and solitary if performed more than 6 months after cataract surgery. Possible confounders, including a history of diabetes in the recipient, were tracked. Macular optical coherence tomography was performed to detect CME 1 month after DMEK if the best-corrected visual acuity was ≤20/30 with a clear cornea with no other reason for visual compromise. RESULTS: A total of 173 eyes from 140 patients were included in the statistical analysis. Staged DMEK was performed in 88 eyes (50.8%) and solitary DMEK in 85 eyes (49.2%). The incidence of CME was 8.0% (7 of 88 eyes) in the staged DMEK group and 7.1% (6 of 85 eyes) in the solitary DMEK group (P = 0.823). The incidence of CME did not differ significantly between the staged and solitary DMEK groups regardless of the recipient diabetic status. All cases of CME resolved within 6 months on topical therapy. CONCLUSIONS: The incidence of postoperative CME after DMEK is similar in the setting of recent or remote cataract surgery.

Microbial Keratitis and Endophthalmitis After the Boston Type 1 Keratoprosthesis.

PURPOSE: To determine the incidence, ocular surface disease associations, microbiological profile, and clinical course of postoperative infections after implantation of the Boston type 1 keratoprosthesis (KPro-1). METHODS: A retrospective chart review was conducted of all cases of the KPro-1 performed at a tertiary eye care center between January 1, 2008, and December 31, 2014. RESULTS: Seventy-five KPro-1 procedures were included in the analysis. Postoperative infections occurred in 13 eyes (17.3%) with an incidence of 0.064 cases per eye-year. The Kaplan-Meier probability of an infection-free graft was 0.96, 0.90, 0.88, 0.87, and 0.86 at years 1 through 5, respectively. The rate of infections was greater in eyes with ocular surface disease (26.3% vs. 8.1%, P = 0.06), especially in those with a history of chemical or thermal injury or herpes zoster keratopathy (P = 0.001). There were 8 cases (10.7%) of microbial keratitis due to either fungi (5 cases) or bacteria (3 cases). There were 7 cases (9.3%) of endophthalmitis due to bacteria (5 cases) or intraocular extension of fungal keratitis (2 cases). The incidence of microbial keratitis and endophthalmitis was 0.034 and 0.03 cases per eye-year, respectively. Therapeutic management of the infected eyes required graft and device removal in 7 eyes (53.8%). After completion of microbiologic treatment, 7 eyes (53.8%) had lost more than 2 lines of the best-corrected preinfection visual acuity, including 5 eyes with endophthalmitis that had hand motion vision or worse. CONCLUSIONS: Postoperative infections are a serious issue that compromises device retention and visual outcomes after keratoprosthesis implantation.

Boston type 1 keratoprosthesis for failed keratoplasty.

The purpose of this study was to evaluate the outcomes of the Boston type 1 keratoprosthesis (Kpro-1) in eyes with failed keratoplasty. A retrospective review was performed of every patient treated with a Kpro-1 at a tertiary eye care center between January 1, 2008 and July 1, 2013. Eyes with a failed keratoplasty originally performed for corneal edema, trauma, or keratoconus were included in the statistical analysis. The main outcome measures were visual outcome, prosthesis retention, and postoperative complications. Twenty-four eyes met the inclusion criteria, including 13 eyes with corneal edema, 8 eyes with trauma, and 3 eyes with keratoconus. After a mean follow-up period of 28.9 months (range 7-63 months), the median best corrected visual acuity (BCVA) was 20/125. The BCVA was ≥ 20/40 in 4 (16.7 %) eyes, ≥ 20/70 in 9 (37.5 %) eyes, and ≥ 20/200 in 14 (58.3 %) eyes. Overall, the postoperative BCVA improved in 17 (70.9 %) eyes, was unchanged in 3 (12.5 %) eyes, and was worse in 4 (16.7 %) eyes. The initial Kpro-1 was retained in 22 (91.7 %) eyes, and was successfully repeated in the other 2 eyes. One or more serious prosthesis- or sight-threatening complications occurred in 8 (33.3 %) eyes. These included 1 case of wound dehiscence leading to prosthesis extrusion, 1 case of fungal keratitis leading to prosthesis extrusion, 4 cases of endophthalmitis, and 5 retinal detachments. The Boston Kpro-1 is associated with an excellent prognosis for prosthesis retention and satisfactory visual improvement in eyes with previous failed keratoplasty.

Boston type 1 keratoprosthesis for primary congenital glaucoma.

BACKGROUND/AIMS: To evaluate the Boston type 1 keratoprosthesis (KPro-1) in treatment of eyes with primary congenital glaucoma. METHODS: A retrospective review was performed of every eye with congenital glaucoma that was treated with a KPro-1 at a tertiary eye care centre between 1 January 2008 and 1 July 2014. The main outcome measures were visual outcome, prosthesis retention and postoperative complications. RESULTS: Six eyes of six patients met the inclusion criteria. This included two paediatric patients, aged 6 months and 6 years, and four adults who were 27-33 years of age. Preoperatively, the best corrected visual acuity (BCVA) was worse than 20/400 in every eye. Three eyes had hand motions and one eye had light perception vision. After a mean follow-up period of 31 months (range 16-51 months), three eyes (50.0%) had a BCVA that was ≥20/400. Overall, the BCVA improved in four eyes (66.7%), and remained the same in two eyes (33.3%). The device was retained in six eyes (83.3%). One or more complications occurred in five eyes (83.3%) and included sterile corneal ulceration (three eyes), retroprosthetic membrane formation (three eyes), progressive glaucomatous optic neuropathy (two eyes), device extrusion (one eye) and an epiretinal membrane (one eye). CONCLUSIONS: The Boston KPro-1 has an excellent prognosis for retention in eyes with congenital glaucoma. The visual prognosis remains guarded due to the high prevalence of pre-existing ocular comorbidity and the common occurrence of sight-threatening postoperative complications.

A Simple and Reliable Technique to Orient Donor Corneal Tissue Using the Radial Width of the Surgical Limbus.

PURPOSE: To develop a method based on identification of the widest region of the surgical limbus that can yield quick and accurate orientation of excised human donor corneas. METHODS: Corneoscleral tissue from donors 49 to 75 years old was marked at the temporal sclera at the time of recovery. Digital images obtained from 20 corneas stored in viewing chambers, retroilluminated and viewed from the endothelial side, were used to quantify the per-degree radial width of the surgical limbus, defined as the distance from the scleral spur to clear cornea. To evaluate differences in radial width among regions, measurements were compared with the intracorneal mean limbal width, and a per-degree z-score was calculated by averaging among corneas. Using images of corneas with the temporal mark masked and the sidedness known, 6 observers were subjected to a blinded trial of 10 corneas to determine the central point of the widest limbal region of each cornea. RESULTS: Compared with the intracorneal mean, the mean radial width of the surgical limbus was greatest in the superior quadrant, and the difference compared with the inferior, nasal, and temporal quadrants was significant (P < 0.0001). The superior region was identified with 100% accuracy in blinded trials. The average absolute difference between the predicted and actual central point of the superior limbus was 9.75 ± 0.30 degrees. CONCLUSIONS: The radial width of the surgical limbus is greatest in the superior region of the cornea and can be used as a diagnostic feature to orient donor corneal tissue.

Boston Type 1 Keratoprosthesis for Iridocorneal Endothelial Syndromes.

PURPOSE: To evaluate the outcome of the Boston type 1 keratoprosthesis (KPro-1) in eyes with iridocorneal endothelial syndromes and failed keratoplasties. METHODS: A retrospective review was performed of every eye with a history of iridocorneal endothelial syndrome and a failed corneal transplant that was treated with a KPro-1 at a tertiary eye care center between January 1, 2008, and July 1, 2014. The main outcome measures were visual outcome, prosthesis retention, and postoperative complications. RESULTS: Four eyes met the inclusion criteria. Two eyes had essential iris atrophy and 2 eyes had Chandler syndrome. All 4 eyes had failed corneal transplants and successful glaucoma drainage devices. The mean patient age at the time of KPro-1 surgery was 68.3 years (range, 60-80 years). The mean postoperative follow-up duration was 47 months (range, 27-69 months). Preoperatively, the best-corrected visual acuity (BCVA) was worse than 20/200 in all 4 eyes, including 2 eyes that had hand motions vision. After KPro-1, all 4 eyes initially obtained a BCVA of ≥20/70. At the most recent examination, the BCVA was still ≥20/100 in 3 eyes. The KPro-1 device was retained in all 4 eyes. Postoperative complications included glaucoma progression (1 eye), a retroprosthetic membrane (1 eye), and sterile vitritis (1 eye). CONCLUSIONS: The Boston KPro-1 may offer a better prognosis than repeat traditional keratoplasty in reestablishing corneal clarity in eyes with iridocorneal endothelial syndromes. Despite anatomic success, visual rehabilitation may be compromised by preexisting glaucomatous optic neuropathy and its postoperative progression.

Regional assessment of energy-producing metabolic activity in the endothelium of donor corneas.

PURPOSE: We characterized mitochondrial respiration and glycolysis activity of human corneal endothelium, and compared metabolic activity between central and peripheral regions. METHODS: Endothelial keratoplasty-suitable corneas were obtained from donors aged 50 to 75 years. The endothelium-Descemet membrane complex (EDM) was isolated, and 3-mm punches were obtained from central and peripheral regions. Endothelium-Descemet membrane punches were assayed for mitochondrial respiration (oxygen consumption) and glycolysis (extracellular acidification) using an extracellular flux analyzer. Enzymatic (citrate synthase, glucose hexokinase) and mitochondrial density (MitoTracker) assays also were performed. RESULTS: Ten corneas were analyzed per assay. Metabolic activity for mitochondrial respiration and glycolysis showed expected changes to assay compounds (P < 0.01, all pairwise comparisons). Basal mitochondrial respiration and glycolysis activity did not differ between regions (P > 0.99). Similarly, central versus peripheral activity after assay compound treatment showed no significant differences (P > 0.99, all time points). The intracorneal coefficient of variation for basal readings between two and four peripheral punches was 18.5% of the mean. Although peripheral samples displayed greater enzymatic activity than central samples (P < 0.05), similar to extracellular flux results, mitochondrial density did not differ between regions (P = 0.78). CONCLUSIONS: Extracellular flux analysis of oxygen and pH is a valid technique for characterizing metabolic activity of human corneal endothelium. This technique demonstrates high reproducibility, allows quantification of metabolic parameters using small quantities of live cells, and permits estimation of overall metabolic output. Neither oxygen consumption nor extracellular acidification differed between central and peripheral regions of transplant suitable corneas in this series. Our results show that endothelial cell health can be quantified biochemically in transplant suitable corneas.

Graft survival of diabetic versus nondiabetic donor tissue after initial keratoplasty.

PURPOSE: To compare corneal graft survival using tissue from diabetic and nondiabetic donors in patients undergoing initial Descemet stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty (PKP). METHODS: A retrospective chart review of pseudophakic eyes that underwent DSAEK or PKP was performed. The primary outcome measure was graft failure. Cox proportional hazard regression and Kaplan-Meier survival analyses were used to compare diabetic versus nondiabetic donor tissue for all keratoplasty cases. RESULTS: A total of 183 eyes (136 DSAEK, 47 PKP) were included in the statistical analysis. Among 24 procedures performed using diabetic donor tissue, there were 4 cases (16.7%) of graft failure (3 DSAEK, 1 PKP), and among 159 procedures performed using nondiabetic donor tissue, there were 18 cases (11.3%) of graft failure (12 DSAEK, 6 PKP). Cox proportional hazard ratio of graft failure for all cases comparing diabetic with nondiabetic donor tissue was 1.69, but this difference was not statistically significant (95% confidence interval, 0.56-5.06; P = 0.348). There were no significant differences in Kaplan-Meier curves comparing diabetic with nondiabetic donor tissue for all cases (P = 0.380). Statistical analysis of graft failure by donor diabetes status within each procedure type was not possible because of the small number of graft failure events involving diabetic tissue. CONCLUSIONS: We found similar rates of graft failure in all keratoplasty cases when comparing tissue from diabetic and nondiabetic donors, but further investigation is needed to determine whether diabetic donor tissue results in different graft failure rates after DSAEK compared with PKP.

Treatment of acanthamoeba keratitis with intravenous pentamidine before therapeutic keratoplasty.

PURPOSE: The aim of this study was to evaluate the outcome of pretreatment of Acanthamoeba keratitis with intravenous pentamidine (IVP) before therapeutic keratoplasty (TKP). METHODS: A retrospective chart review was performed of the medical records of every patient treated with IVP before TKP for Acanthamoeba keratitis at a single, tertiary care eye center between January 1, 2002, and December 31, 2012. The main outcome measures were microbiological cure, graft survival, and visual outcome. RESULTS: Eight eyes of 7 patients met the inclusion criteria. Preoperatively, all 8 eyes had failed traditional antiamoebic therapy, including 5 eyes with recurrent infections after previous TKP. The patients were treated with IVP (190-400 mg/d) for a median of 14 days (range, 7-26 days). After 8 TKP, a microbiological cure was achieved, and a clear graft was maintained in 5 (62.5%) eyes during a mean follow-up interval of 31.2 months (range, 1.0-95.7 months). Repeat TKP in 3 eyes with recurrent Acanthamoeba keratitis resulted in 2 additional microbiological cures and 1 more clear graft. The final best-corrected visual acuity was ≥20/40 in 5 (62.5%) eyes and worse than 20/200 in 3 eyes. Overall, the final vision was improved in 6 (75.0%) eyes, remained the same in 1 (12.5%) eye, and was worse in 1 (12.5%) eye. CONCLUSIONS: The adjunctive use of IVP before TKP may assist with the achievement of microbiological cure, clear graft, and good visual outcome in a majority of eyes with Acanthamoeba keratitis.

Diabetes mellitus increases risk of unsuccessful graft preparation in Descemet membrane endothelial keratoplasty: a multicenter study.

PURPOSE: The aim of this study was to evaluate preparation outcomes of tissue prepared for Descemet membrane endothelial keratoplasty (DMEK) from diabetic and nondiabetic donors. METHODS: In this nonrandomized, consecutive case series, DMEK grafts were prepared from diabetic and nondiabetic donors by experienced technicians in 2 eye banks using slightly different, modified submerged manual preparation techniques to achieve "prestripped" graft tissue. Graft preparation results were analyzed retrospectively. The main outcome measure was the rate of unsuccessful (failed) DMEK graft preparations, defined as tears through the graft area that prevent tissue use. RESULTS: A total of 359 corneas prepared from 290 donors (114 diabetic and 245 nondiabetic) were included in the statistical analysis of graft preparation failure. There were no significant differences between diabetic and nondiabetic donor tissue characteristics with respect to donor age, death to preservation time, death to preparation time, endothelial cell density, percent hexagonality, or coefficient of variation. DMEK tissue preparation was unsuccessful in 19 (5.3%) cases. There was a significant difference in the site-adjusted rate of DMEK preparation failure between diabetic [15.3%; 95% confidence interval (CI), 9.0-25.0] and nondiabetic donors (1.9%; 95% CI, 0.8-4.8), and the corresponding site-adjusted odds ratio of DMEK graft preparation failure in diabetic donor tissue versus nondiabetic donor tissue was 9.20 (95% CI, 2.89-29.32; P = 0.001). CONCLUSIONS: Diabetes may be a risk factor for unsuccessful preparation of donor tissue for DMEK. We recommend caution in the use of diabetic tissue for DMEK graft preparation. Further study is needed to identify what subset of diabetic donors is at risk for unsuccessful DMEK graft preparation.

Boston type 1 keratoprosthesis for chemical and thermal injury.

PURPOSE: To evaluate the outcome of the Boston type 1 keratoprosthesis (Kpro-1) in eyes with failed interventions for chemical and thermal injury. METHODS: A retrospective review was performed of every eye with chemical or thermal injury that was treated with a Kpro-1 at a tertiary eye care center between January 1, 2008 and July 1, 2013. The main outcome measures were visual outcome, prosthesis retention, and postoperative complications. RESULTS: Nine eyes met the inclusion criteria, including 7 eyes with alkali burns, 1 eye with an acid burn, and 1 eye with a thermal burn. After a mean follow-up of 40.7 months (range, 29-60 months), the median best-corrected visual acuity was 20/60 (range, 20/15 to no light perception). One eye was ≥20/20, 3 eyes were ≥20/40, and 6 eyes were ≥20/70. The initial Kpro-1 prosthesis was retained in 7 (77.7%) eyes and successfully replaced in the other 2 eyes. One or more serious complications occurred in 6 (66.7%) eyes. These included 2 cases of sterile corneal ulceration with prosthesis extrusion, 2 cases of microbial keratitis (1 bacterial and 1 fungal), 2 cases of bacterial endophthalmitis, and 2 cases of retinal detachments. These complications contributed to visual outcomes of hand motions in 2 eyes and no light perception in 1 eye. CONCLUSIONS: The Boston Kpro-1 is associated with highly satisfactory visual outcomes and prosthesis retention in most cases of severe chemical or thermal injury. Serious complications are common and may compromise the final outcome.

Graft survival versus glaucoma treatment after penetrating or Descemet stripping automated endothelial keratoplasty.

PURPOSE: The aim of this study was to assess and compare the association of glaucoma therapy with graft survival after performing penetrating keratoplasty (PKP) and Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: A retrospective chart review was performed of cases: primary PKP from January 1, 2003, to December 31, 2005, or primary DSAEK from January 1, 2006, to December 31, 2008. Eyes with a surgical indication of pseudophakic corneal edema were included in the statistical analysis. Eyes were stratified by glaucoma treatment into those with (1) no glaucoma treatment, (2) medical therapy only, or (3) surgical intervention. The main outcome measure was graft survival. RESULTS: Fifty-seven PKP-operated and 156 DSAEK-operated eyes met the inclusion criteria. After PKP and DSAEK, respectively, the 5-year Kaplan-Meier graft survival was 94.7% and 93.8% in eyes with no glaucoma treatment (P > 0.99), 93.8% and 96.3% in eyes with medical therapy only (P > 0.99), and 56.8% and 50% in eyes with surgical intervention (P > 0.99). After both procedures were performed, graft survival was significantly worse in eyes with surgical intervention compared with that in eyes with no glaucoma treatment (P < 0.0001) or in eyes with medical therapy alone (P < 0.0001). CONCLUSIONS: PKP and DSAEK have comparable graft survival in eyes without glaucoma management and in those with comparable glaucoma management.

Boston keratoprosthesis type 1 for herpes simplex and herpes zoster keratopathy.

PURPOSE: The aim of this study was to evaluate and compare the outcomes of Boston keratoprosthesis type 1 (Kpro-1) in eyes with herpes simplex virus (HSV) and herpes zoster virus (HZV) keratopathy. METHODS: A retrospective review was performed of the medical records of every patient treated with a Boston Kpro-1 at the University of Iowa Hospitals and Clinics between January 1, 2008 and July 1, 2012. Eyes with visual loss due to HSV or HZV keratopathy were included in the statistical analysis. The main outcome measures were graft retention, postoperative complications, and visual outcome. RESULTS: Nine eyes met the inclusion criteria, including 5 eyes in the HSV group and 4 eyes in the HZV group. The graft retention rate was 100% in the HSV group after a mean follow-up of 48.4 months, compared with 25% in the HZV group after 50.5 months (P = 0.048). There were 3 cases of microbial keratitis, including 2 eyes that also developed endophthalmitis, in the HZV group, compared with no cases in the HSV group (P = 0.048). There was significantly better best-corrected visual acuity at the most recent examination in the HSV group than in the HZV group (P = 0.019). All 5 HSV eyes had improved best-corrected visual acuity compared with preoperative acuity, whereas only 1 HZV eye experienced a similar result (P = 0.048). CONCLUSIONS: Kpro-1 is associated with an excellent prognosis for graft retention, acceptably low prevalence of sight-threatening complications, and highly satisfactory visual improvement in eyes with HSV keratopathy, but not in eyes with HZV keratopathy.

Outcomes of treatment of fungal keratitis at the University of Iowa Hospitals and Clinics: a 10-year retrospective analysis.

PURPOSE: To evaluate the outcomes of medical and surgical management of fungal keratitis at a tertiary care eye center. METHODS: A retrospective review was performed of the medical records of all patients with a diagnosis of microbiologically or histopathologically confirmed fungal keratitis at the University of Iowa Hospitals and Clinics from July 1, 2001, through June 30, 2011. The main outcome measure was a microbiological cure with either medical therapy alone or medical therapy combined with therapeutic keratoplasty (TKP). The secondary outcome measures were graft survival of the TKPs and subsequent optical keratoplasties (OKPs) and visual outcome. RESULTS: Seventy-three eyes met the inclusion criteria. A microbiological cure was achieved in 72 eyes (98.6%). Forty-one eyes (56.2%) were treated with medical therapy alone, and 32 (43.8%) eyes required 1 TKP (29 eyes) or 2 TKPs (3 eyes). Among the 32 eyes treated with TKP, 17 (53.1%) maintained a clear graft. Among 15 eyes with failed grafts, 12 eyes ultimately achieved clear grafts after a total of 19 OKP procedures. Among 41 eyes treated with medical therapy alone, all 3 eyes treated with OKP remained clear. The final median best-corrected visual acuity was 20/30 in the medical therapy group and 20/40 in the TKP group. CONCLUSIONS: A high microbiological cure rate can be achieved in eyes with fungal keratitis; however, TKP is often needed to achieve this objective. A good final visual outcome can be achieved in most cases, but multiple keratoplasty procedures may be required.

Treatment of aniridia with Boston type I keratoprosthesis.

PURPOSE: To report the outcomes of Boston keratoprosthesis (K-pro) type I implantation for congenital aniridia. METHODS: A retrospective review of the medical records of every patient with congenital aniridia who underwent Boston K-pro type I implantation at the University of Iowa Hospitals and Clinics from January 1, 2009, through December 31, 2011 was performed. The main outcome measures were visual acuity, graft retention, and postoperative complications. RESULTS: A total of 7 eyes (7 patients) met the inclusion criteria. The mean patient age was 52 years (range, 12-85 years). The preoperative visual acuity was 20/1600 in 6 eyes (85.7%) and hand motions in 1 eye (14.3%). After a median follow-up period of 18 months (range, 3-30 months), the median final best spectacle-corrected visual acuity was 20/200 (range, 20/100 to light perception). This included 2 eyes (28.6%) that were 20/100 and 5 eyes (71.4%) that were better than 20/300. Compared with the preoperative best spectacle-corrected visual acuity, the final vision was improved in 6 eyes (85.7%) and worse in 1 eye (14.3%). The K-pro graft was retained in all 7 eyes (100%). The most common complication was the formation of a retroprosthetic membrane in 3 eyes (42.9%), none of which required either a YAG capsulotomy or a vitrectomy. One eye (14.3%) developed a wound dehiscence that required surgical repair. CONCLUSIONS: The Boston K-pro type I is a good option for the visual rehabilitation of eyes with congenital aniridia.

Confirmation of the association between the TCF4 risk allele and Fuchs endothelial corneal dystrophy in patients from the Midwestern United States.

PURPOSE: To determine the role of the single nucleotide polymorphism (SNP) (rs613872) in the TCF4 gene in Fuchs endothelial corneal dystrophy (FECD) in patients from Iowa. METHODS: A cohort of 82 patients with FECD and 163 normal control subjects from Iowa were genotyped at the SNP rs613872 using a real-time allelic discrimination assay. RESULTS: The frequencies of the alleles of rs613872 were compared between FECD patients and control subjects. A highly significant association (p-value = 2.96 × 10(-10)) was detected between this SNP and FECD. Comparison of the genotypes of SNP rs613872 between FECD patients and control subjects produced a p-value of 2.43 × 10(-10). CONCLUSION: Prior reports have shown that SNP rs613872 in the TCF4 gene is highly associated with FECD. Our study confirms this association and shows that the TCF4 gene has an important role in the pathogenesis of corneal disease in patients from Iowa.