Graft Survival, Graft Rejection, and Glaucoma in a Consecutive Series of Descemet Stripping Endothelial Keratoplasty.

PURPOSE: The goal of this study was to compare outcomes of Descemet stripping endothelial keratoplasty (DSEK) in eyes with glaucoma and abnormal anatomy to eyes with Fuchs endothelial corneal dystrophy (FECD). METHODS: In a retrospective interventional series of all cases of DSEK between April 1, 2006, and November 30, 2015, recipient diagnosis, preoperative glaucoma status, concurrent surgical procedures, and graft outcomes were recorded. Graft survival, risk of rejection, and subsequent glaucoma surgery were estimated by using Kaplan-Meier analysis with risk factors determined by proportional hazard models. RESULTS: Of 703 DSEKs in 666 eyes (509 subjects), the main recipient diagnoses were FECD (n = 496), pseudophakic corneal edema (n = 112), and failed graft (n = 83). Glaucoma was present in 150 cases before DSEK. Overall graft survival was 85%, 75%, and 71% at 5, 10, and 12 years, respectively, and for FECD without glaucoma was 95%, 89%, and 87% at 5, 10, and 12 years, respectively. Independent risk factors for graft failure included recipient diagnoses of pseudophakic corneal edema (HR = 8.3, P < 0.001), failed graft (HR = 6.4, P < 0.001), and preoperative medical glaucoma (HR = 7.1, P < 0.001) or surgical glaucoma (HR = 12.3, P < 0.001). Preoperative glaucoma treated by previous surgery resulted in graft survival of 28% at 10 years. Preoperative glaucoma was associated with an increased risk of graft rejection (HR = 6.8, P < 0.001) and subsequent glaucoma surgery (HR > 17.4, P < 0.001). CONCLUSIONS: Preoperative glaucoma increases the risk of graft failure, graft rejection, and needing subsequent glaucoma surgery in the first decade after DSEK. With previous glaucoma surgery, DSEK graft survival was more favorable compared with published reports of Descemet membrane endothelial keratoplasty.

Oxalosis Associated With High-Dose Vitamin C Ingestion in a Peritoneal Dialysis Patient.

We report a case of systemic oxalosis involving the eyes and joints due to long-term use of high-dose vitamin C in a patient receiving maintenance peritoneal dialysis (PD). This 76-year-old woman with autosomal dominant polycystic kidney disease underwent living unrelated kidney transplantation 10 years earlier. The transplant failed 6 months before presentation, and she initiated hemodialysis therapy before transitioning to PD therapy 4 months later. During the month before presentation, the patient noted worsening arthralgias and decreased vision. Ophthalmologic examination revealed proliferative retinopathy and calcium oxalate crystals. Plasma oxalate level was markedly elevated at 187 (reference range, <1.7) µmol/L, and urine oxalate-creatinine ratio was high (0.18mg/mg). The patient reported taking up to 4g of vitamin C per day for several years. Workup for causes of primary and secondary hyperoxaluria was otherwise negative. Vitamin C use was discontinued, and the patient transitioned to daily hemodialysis for 2 weeks. Plasma oxalate level before the dialysis session decreased but remained higher (30-53µmol/L) than typical for dialysis patients. Upon discharge, the patient remained on thrice-weekly hemodialysis therapy with stabilized vision and improved joint symptoms. This case highlights the risk of high-dose vitamin C use in patients with advanced chronic kidney disease, especially when maintained on PD therapy.

Healthcare Utilization by Glaucoma Patients in a Team Care Model.

PURPOSE: To determine the effect of a glaucoma team care model on resource utilization and efficiency in glaucoma management. METHODS: Retrospective cohort study of 358 patients diagnosed and treated for glaucoma. Analysis included number of patient visits, diagnostic tests, and glaucoma procedures performed before (2005-2007) and after (2008-2010) implementation of a team care model in 2008. Patients not involved in the model served as controls. RESULTS: Number of patient visits did not change significantly after model implementation (p > .05). Diagnostic tests significantly increased in comprehensive ophthalmologist and glaucoma subspecialist groups 25 months after diagnosis (p = .03 and p = .001). Procedures increased for glaucoma subspecialists but was not statistically significant (p = .06). Optometrists used billing codes with significantly lower reimbursement than other providers (p < .001). CONCLUSIONS: Team care model had neutral effect on patient visits and increased testing. Continued evaluation of this model is required to determine its effect on disease progression and outcomes.

Fuchs' Endothelial Corneal Dystrophy in Patients With Myotonic Dystrophy, Type 1.

Purpose: RNA toxicity from CTG trinucleotide repeat (TNR) expansion within noncoding DNA of the transcription factor 4 (TCF4) and DM1 protein kinase (DMPK) genes has been described in Fuchs' endothelial corneal dystrophy (FECD) and myotonic dystrophy, type 1 (DM1), respectively. We prospectively evaluated DM1 patients and their families for phenotypic FECD and report the analysis of CTG expansion in the TCF4 gene and DMPK expression in corneal endothelium. Methods: FECD grade was evaluated by slit lamp biomicroscopy in 26 participants from 14 families with DM1. CTG TNR length in TCF4 and DMPK was determined by a combination of Gene Scan and Southern blotting of peripheral blood leukocyte DNA. Results: FECD grade was 2 or higher in 5 (36%) of 14 probands, significantly greater than the general population (5%) (P < 0.001). FECD segregated with DM1; six of eight members of the largest family had both FECD and DM1, while the other two family members had neither disease. All DNA samples from 24 subjects, including four FECD-affected probands, were bi-allelic for nonexpanded TNR length in TCF4 (<40 repeats). Considering a 75% prevalence of TCF4 TNR expansion in FECD, the probability of four FECD probands lacking TNR expansion was 0.4%. Neither severity of DM1 nor DMPK TNR length predicted the presence of FECD in DM1 patients. Conclusions: FECD was common in DM1 families, and the diseases cosegregated. TCF4 TNR expansion was lacking in DM1 families. These findings support a hypothesis that DMPK TNR expansion contributes to clinical FECD.

Analysis of a Physician-led, Team-based Care Model for the Treatment of Glaucoma.

PURPOSE: To determine the effect of a protocol for a new physician-led, team-based glaucoma care model implemented in 2008 at Mayo Clinic's campus in Rochester, Minnesota (MCR), to increase conformance with the American Academy of Ophthalmology (AAO) Preferred Practice Pattern guidelines for treatment of primary open-angle glaucoma. METHODS: Records of 591 patients with newly diagnosed glaucoma were assessed retrospectively for the completion of 9 AAO Preferred Practice Pattern recommended metrics including measured corneal thickness, intraocular pressure (IOP), cup to disk ratio, visual acuity, recorded IOP target, gonioscopy, fundus photos, ocular coherence tomography, and visual field in the 3 years before and 3 years after protocol implementation. Treatment by the glaucoma care team at MCR was compared with treatment at a community-based general ophthalmology practice and with a group of comprehensive ophthalmologists at MCR without team care, which served as controls. RESULTS: Adherence to AAO recommendations increased for the documentation of target IOP (+24%, 42.6% to 66.7%; P=0.007), gonioscopy (+27%, 66.7% to 93.3%; P≤0.001), fundus photos (+29%, 44.4% to 73.3%; P≤0.001), and ocular coherence tomography (+20%, 48.1% to 68.0%; P=0.02) after protocol initiation. No change in pattern of testing occurred in the control groups without team care during the same time period. Type and severity of glaucoma were similar between MCR and community practice. CONCLUSIONS: An increase in compliance with AAO guidelines was found after implementation of our protocol for a physician-led, team-based care model to standardize glaucoma care among providers.

Stanniocalcin-1 Is an Ocular Hypotensive Agent and a Downstream Effector Molecule That Is Necessary for the Intraocular Pressure-Lowering Effects of Latanoprost.

Purpose: To identify downstream signaling molecules through which intraocular pressure (IOP) is lowered following treatment with the prostaglandin analog latanoprost. Methods: Total RNA and protein isolated from primary human Schlemm's canal cells (n = 3) treated with latanoprost (free acid; 100 nM) were processed for quantitative PCR and Western blot analysis. IOP was evaluated in stanniocalcin-1 (STC-1-/-) and wild-type mice following treatment with latanoprost or Rho kinase inhibitor Y27632. Human anterior segment pairs (n = 8) were treated with recombinant STC-1 (5, 50, or 500 ng/mL) and pressure was recorded using custom-designed software. The effect of recombinant STC-1 (0.5 mg/mL) on IOP was evaluated in wild-type mice. Tissue morphology was evaluated by light and transmission electron microscopy. Results: Increased STC-1 mRNA (4.0- to 25.2-fold) and protein expression (1.9- to 5.1-fold) was observed within 12 hours following latanoprost treatment. Latanoprost reduced IOP in wild-type mice (22.0% ± 1.9%), but had no effect on STC-1-/- mice (0.5% ± 0.7%). In contrast, Y27632 reduced IOP in both wild-type (12.5% ± 1.2%) and in STC-1-/- mice (13.1% ± 2.8%). Human anterior segments treated with STC-1 (500 ng/mL) showed an increase in outflow facility (0.15 ± 0.03 to 0.27 ± 0.09 µL/min/mm Hg) while no change was observed in paired vehicle-treated controls. Recombinant STC-1 reduced IOP in wild-type mice by 15.2% ± 3.0%. No observable morphologic changes were identified between treatment groups when evaluated by microscopy. Conclusions: Latanoprost-induced reduction of IOP is mediated through the downstream signaling molecule STC-1. When used by itself, STC-1 exhibits ocular hypotensive properties.

Effects of prostaglandin analogues on aqueous humor outflow pathways.

Elevated intraocular pressure (IOP) is the most prevalent risk factor for glaucoma. All treatments, whether surgical or pharmaceutical, are aimed at lowering IOP. Prostaglandin analogues are a first line therapy for glaucoma due to their ability to reduce IOP, once-daily dosing, efficacy, and minimal side-effect profile. Whereas prostaglandin analogues have been known to alter aqueous humor outflow through the unconventional (uveoscleral) pathway, more recent evidence suggests their action also occurs through the conventional (trabecular) pathway. Understanding how prostaglandin analogues successfully lower IOP is important, as this information may lead to the discovery of new molecular targets for future therapeutic intervention. This review explores the current understanding of prostaglandin analogue biology as it pertains to IOP reduction and improved aqueous humor outflow facility.

Pulse duration and energy dependence of photodamage and lethality induced by femtosecond near infrared laser pulses in Drosophila melanogaster.

The potential application of nonlinear optical imaging diagnosis and treatment using femtosecond laser pulses in humans accentuates the need for studies carried out in whole organisms instead of single cells or cell cultures. While there is a general consensus that in order to minimize the level of photodamage the excitation power has to be kept as low as possible, it has yet to be determined if shorter pulses have greater benefit than longer pulses. Here we evaluate the rate of death in Drosophila melanogaster as the integral parameter related to photodamage resulting from femtosecond near infrared (NIR) laser irradiation under conditions comparable to those used in two-photon excited fluorescence (TPEF) microscopy. We found that the lethality (resulting from photodamage) as a function of laser energy fluence fits a 3-region dose-response curve. The lethality was accompanied with development of necrosis and apoptosis in irradiated tissues. Quantitative analysis showed that the damage has a mostly linear character on energy fluence per pulse, and for a given TPEF signal, shorter (37 fs) pulse duration results in lower lethality than longer (100 fs) pulse duration. These results have important implications for the use of femtosecond NIR laser pulses in microscopy as well as in vivo medical imaging.

Applications of femtochemistry to proteomic and metabolomic analysis.

Femtosecond laser pulses have been widely used as a tool to study molecular ionization and fragmentation. This article bridges the application of femtosecond laser technology in early research focused on small isolated molecules with that in modern biological mass spectrometry for proteomics and metabolomic analysis on large (140+ atoms) biomolecules. The single-shot interaction of a femtosecond laser with neutral para-nitrotoluene (pNT) is investigated with time-of-flight mass spectrometry and compared with the ultrafast photodissociation of protonated pNT in an ion trap mass spectrometer accumulated over ∼1000 pulses. The ion trap experiment is then extended to longer biomolecules. As demonstrated in the examples of vasopressin and tomatine, this novel ion activation method provides greater sequence coverage and nonstatistical fragmentation, leading to valuable information complementary to conventional methods for structural analysis.