Prospective Randomized Trial of Corneal Cross-linking Riboflavin Dosing Frequencies for Treatment of Keratoconus and Corneal Ectasia.

PURPOSE: To investigate whether the riboflavin dosing frequency affects corneal cross-linking efficacy or safety, given that isotonic riboflavin solution is viscous and each installation coats the corneal surface with a film that absorbs some of the incident ultraviolet A light. DESIGN: Prospective, randomized, single-center equivalence trial. PARTICIPANTS: Patients with progressive keratoconus or ectasia after refractive surgery (n = 510). METHODS: One eye per patient was prospectively randomized to 2-minute or 5-minute riboflavin dosing intervals with standard corneal cross-linking (epithelial removal and 30-minute irradiation with 3 mW/cm2 ultraviolet A light). Block randomization resulted in comparable representation of keratoconus and ectasia after refractive surgery in the 2 treatment arms. Treatment equivalence was assessed using the 2 one-sided test. Fellow eyes (n = 207) were treated with 5-minute dosing and considered in the safety analysis. MAIN OUTCOME MEASURES: The primary hypothesis was equivalent change in the topography-derived maximum keratometry value from baseline to 6 months with 2-minute vs. 5-minute dosing. A ±0.75-diopter margin of equivalence for the treatment difference between dosing regimens was considered clinically relevant. Adverse events and changes from baseline to 6 months in corrected distance visual acuity (CDVA), uncorrected distance visual acuity, and minimum corneal thickness were assessed. RESULTS: The mean reduction in maximum keratometry from baseline was equivalent with 2-minute and 5-minute riboflavin dosing intervals at 6 months (0.97 and 0.76 diopters, respectively; 90% confidence interval for treatment difference, -0.23 to 0.66; per-protocol population). With both dosing intervals, the mean improvement in CDVA was 0.07 logarithm of the minimum angle of resolution or 3.5 letters at 6 months. Of the 635 study and fellow eyes examined at 6 months, 134 (21%) gained and 32 (5%) lost 2 or more lines of CDVA. Three eyes (0.4%) developed sterile infiltrates, 1 (0.1%) had delayed epithelial healing with dendrites, and 3 (0.4%) had recurrent epithelial defects. Three eyes (0.4%) were re-treated. CONCLUSIONS: The 2 riboflavin dosing regimens produced equivalent reduction in the maximum keratometry value, with a favorable safety profile.

Descemet's Membrane Endothelial Keratoplasty: Risk of Immunologic Rejection Episodes after Discontinuing Topical Corticosteroids.

PURPOSE: To assess the risk of immunologic rejection episodes if topical corticosteroids are discontinued 1 year after Descemet's membrane endothelial keratoplasty (DMEK) compared with continued once-per-day use. DESIGN: Prospective, longitudinal, parallel-group study. PARTICIPANTS: A total of 400 eyes of 259 DMEK recipients, aged 23 to 90 years. METHODS: Patients were enrolled 1 year after DMEK and allowed to choose whether to stop or continue once-daily topical corticosteroids to maximize compliance. Fellow eyes were eligible for enrollment because the donor grafts were independent. Participants were examined at 1, 3, 6, and 12 months during the second year after DMEK. Results were assessed using Kaplan-Meier survival analysis. MAIN OUTCOME MEASURES: Incidence of immunologic rejection episodes. RESULTS: Steroids were discontinued in 277 eyes (no steroid group) and continued once per day in 123 eyes (steroid group). The subject demographics were well balanced across groups; 99% of the subjects were white, and 95% of the grafts were performed to treat Fuchs' dystrophy. The cumulative incidence of rejection episodes was significantly greater in the no steroid group (6% vs. 0% in the steroid group; P = 0.013). Thirteen of 14 rejection episodes (all in the no steroid group) resolved with resumption of topical corticosteroids. Overall, 1 of 277 grafts (0.4%) failed in the no steroid group, and none failed in the steroid group during the second year after DMEK (P = 0.49). The endothelial cell loss between 1 and 2 years was comparable in the no steroid and steroid groups (6.4%±12% vs. 5.6%±14%, respectively; P = 0.67). CONCLUSIONS: Continued once-per-day use of a topical corticosteroid, even a weak one, was protective against rejection episodes during the second year after DMEK, whereas 6% experienced a rejection episode when steroids were discontinued. Among the 364 eyes that completed 12 months' follow-up, only 1 graft (0.27%) failed.

Repeat Descemet Membrane Endothelial Keratoplasty: Secondary Grafts with Early Intervention Are Comparable with Fellow-Eye Primary Grafts.

PURPOSE: To evaluate the outcomes of secondary Descemet membrane endothelial keratoplasty (DMEK) after failed primary DMEK. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Fifty-five DMEK recipients 42 to 89 years of age. METHODS: An initial consecutive series of 1655 DMEK surgeries was reviewed to identify cases of secondary DMEK after failed primary DMEK (n = 55). A paired fellow-eye analysis was performed with a subgroup of 29 patients who underwent secondary DMEK in 1 eye and successful primary DMEK in the fellow eye. MAIN OUTCOME MEASURES: Corrected distance visual acuity (CDVA), central corneal thickness, and 1-year endothelial cell loss. RESULTS: The median follow-up after DMEK regraft was 18 months (range, 3-61 months). All 55 regrafts cleared, 8 (15%) had air reinjected to promote attachment, 1 eye (2%) with trabeculectomy and progressive synechiae demonstrated late endothelial failure, and no rejection episodes occurred (0%). In the paired analysis, the median duration of endothelial decompensation before the regraft was 21 days (range, 2-133 days). At 1, 3, 6, or 12 months, CDVA did not differ between the primary and secondary grafts in fellow eyes (mean difference, ≤2 Snellen letters; P > 0.05 at all examinations). At 1 year, the visual acuity was ≥20/20 in 61%, ≥20/25 in 81%, and ≥20/40 in 100% of the secondary grafts in the paired analysis, excluding 1 eye with retinal problems. Vision differed by ≤1 line between fellow eyes in all but the 1 patient with the longest time to regraft (133 days), who demonstrated central haze and irregular astigmatism from anterior stromal scarring during that period. At 1 year, CDVA associated with the scarring was 20/40 versus 20/20 for the fellow-eye primary graft. The central corneal thickness was comparable between fellow-eye primary and secondary grafts at 3, 6, and 12 months (mean difference at 1 year, 2 µm; P = 0.57). The 1-year endothelial cell loss was comparable in primary and secondary grafts (27% vs. 31%, respectively; P = 0.58). CONCLUSIONS: In patients who received prompt intervention to minimize the duration of central corneal decompensation, the visual outcomes with secondary DMEK matched the fellow-eye visual outcomes with primary DMEK.

Prospective Assessment of Loteprednol Etabonate 0.25% for Prevention of Immunologic Rejection After Descemet Membrane Endothelial Keratoplasty in Eyes With Fuchs Dystrophy.

PURPOSE: The purpose of this study was to assess off-label use of loteprednol etabonate 0.25% ophthalmic suspension for prevention of immunologic rejection after Descemet membrane endothelial keratoplasty (DMEK). METHODS: This prospective, open-label study enrolled 70 eyes of 70 participants without preexisting glaucoma 1 month after DMEK. Participants used topical loteprednol 0.25% 4 times daily for 2 months, tapered by 1 drop/month to once daily use, and continued use through 1 year after DMEK. Main outcomes were rate of intraocular pressure (IOP) elevation (defined as a relative increase of ≥10 mm Hg over the pretransplant IOP) and rate of initial allograft rejection episodes. The results were compared with historical data using the log-rank test. RESULTS: All participants had Fuchs dystrophy, and 40 of 70 (57%) were female. None (0%) experienced an immunologic graft rejection episode, matching the previously reported efficacy of prednisolone acetate 1% suspension and loteprednol 0.5% gel (both 0% incidence). One study eye developed IOP elevation 3 months after DMEK (cumulative risk 1.5%). Compared with historical data, this was similar to the risk with loteprednol 0.5% gel (4%, P = 0.36) and significantly lower than the risk with prednisolone 1% suspension (18%, P = 0.0025). Two participants (3%) complained of instillation site discomfort, consistent with the 5% rate reported on package labeling. CONCLUSIONS: Loteprednol 0.25% suspension, approved for short-term treatment of dry eyes, effectively prevented immunologic rejection episodes with minimal risk of IOP elevation when used from 1 month until 12 months after DMEK in patients without preexisting glaucoma.

Proteasome subunit Rpn1 binds ubiquitin-like protein domains.

The yeast protein Rad23 belongs to a diverse family of proteins that contain an amino-terminal ubiquitin-like (UBL) domain. This domain mediates the binding of Rad23 to proteasomes, which in turn promotes DNA repair and modulates protein degradation, possibly by delivering ubiquitinylated cargo to proteasomes. Here we show that Rad23 binds proteasomes by directly interacting with the base subcomplex of the regulatory particle of the proteasome. A component of the base, Rpn1, specifically recognizes the UBL domain of Rad23 through its leucine-rich-repeat-like (LRR-like) domain. A second UBL protein, Dsk2, competes with Rad23 for proteasome binding, which suggests that the LRR-like domain of Rpn1 may participate in the recognition of several ligands of the proteasome. We propose that the LRR domain of Rpn1 may be positioned in the base to allow the cargo proteins carried by Rad23 to be presented to the proteasomal ATPases for unfolding. We also report that, contrary to expectation, the base subunit Rpn10 does not mediate the binding of UBL proteins to the proteasome in yeast, although it can apparently contribute to the binding of ubiquitin chains by intact proteasomes.

Endothelial Keratoplasty Update 2020.

ABSTRACT: Endothelial keratoplasty has revolutionized the treatment of corneal endothelial dysfunction and lowered the threshold for treatment by providing rapid visual rehabilitation and setting a high standard for safety and efficacy. Over time, endothelial keratoplasty techniques have evolved toward the use of thinner tissue to optimize visual outcomes; refinements have facilitated donor tissue preparation, handling, and attachment; and adaptations have expanded utilization in eyes with challenging ocular anatomy. Despite early concerns about graft longevity, emerging 10-year endothelial cell loss and graft survival data have been encouraging. A shortage of human donor corneas restricts utilization in many areas of the world and is driving a search for keratoplasty alternatives. Further work is needed to expand the donor supply, minimize impediments to adoption, optimize graft survival, and improve refractive predictability.

Randomized, Double-Masked Trial of Netarsudil 0.02% Ophthalmic Solution for Prevention of Corticosteroid-Induced Ocular Hypertension.

PURPOSE: To assess whether prophylactic use of netarsudil 0.02% ophthalmic solution reduces the risk of intraocular pressure (IOP) elevation associated with prolonged use of topical corticosteroids to prevent cornea transplantation rejection. DESIGN: Prospective, randomized clinical trial. METHODS: In this study, 120 subjects were randomized to use netarsudil (off-label) or placebo once daily for 9 months after Descemet membrane endothelial keratoplasty, and 71 fellow eyes were enrolled and assigned to the opposite treatment arm. Participants concurrently used topical prednisolone acetate 1% 4× daily for 3 months, 3× daily for a month, twice daily for a month, and once daily for 4 months. The main outcome was IOP elevation (defined as IOP ≥24 mm Hg or an increase of ≥10 mm Hg over baseline) assessed by Kaplan-Meier and proportional hazards analyses, taking loss to follow-up into consideration. RESULTS: Overall, 95 eyes were assigned to netarsudil and 96 to placebo; 15 eyes (16%) were withdrawn early from the netarsudil arm because of ocular irritation. The rate of IOP elevation was 14% with netarsudil and 21% with placebo (relative risk: 0.6; 95% confidence interval: 0.3-1.3; P = .23). IOP was >30 mm Hg in 7.8% assigned to netarsudil versus 7.4% assigned to placebo (P = .84). Median 6-month central endothelial cell loss was 31% versus 29% with netarsudil versus placebo, respectively (P = .49). CONCLUSIONS: Netarsudil did not produce a statistically significant reduction in the risk of steroid-induced IOP elevation after corneal transplantation relative to placebo.

Traumatic flap striae 6 years after LASIK: case report and literature review.

PURPOSE: To report a case of traumatic flap striae without flap dislocation 6 years after LASIK and provide a literature review of surgical flap striae, late traumatic flap striae, and their management. METHODS: A 28-year-old man presented with late traumatic flap striae without concurrent flap dislocation, which closely approximated the longest reported interval between LASIK and the development of flap striae. RESULTS: In the absence of flap dislocation, the finding of striae alone was subtle and went undetected initially. The flap was successfully refloated, stretched, and smoothed with recovery of 20/20 vision. CONCLUSIONS: Traumatic LASIK flap complications may occur many years after the original procedure. This report presents the first case of late traumatic flap striae without concurrent flap dislocation. Proper management can restore good visual function.

Descemet Membrane Endothelial Keratoplasty for Failed Penetrating Keratoplasty: Visual Outcomes and Graft Survival.

PURPOSE: To evaluate outcomes and graft survival of Descemet membrane endothelial keratoplasty (DMEK) for failed penetrating keratoplasty (PK). METHODS: Ninety-three DMEK procedures performed in 84 eyes of 77 patients with failed PK were retrospectively reviewed. The main outcomes were corrected distance visual acuity and graft survival assessed with Kaplan-Meier survival analysis and proportional hazards modeling taking follow-up into consideration. RESULTS: Sixty-nine eyes had 1 previous failed PK, 13 had 2, 1 had 3, and 1 had 4. Ten eyes had failed Descemet stripping endothelial keratoplasty (DSEK) performed under failed PK. Fourteen cases (15%) had previous glaucoma filtration surgery (9 trabeculectomy alone; 5 trabeculectomy and aqueous shunt). Median follow-up was 21 months (range, 1 month to 7 years). Median Snellen corrected distance visual acuity improved from 20/100 preoperatively (range, 20/30 to count fingers) to 20/30 at 6 months postoperatively (n = 73; range, 20/20-20/200). Rebubbling rates were 53% when the diameter of the DMEK graft was oversized, 27% when same sized, and 33% when undersized relative to that of the previous PK graft. Two grafts (2%) experienced an immunologic rejection episode, and 15 (16%) failed, including 5 primary/early failures and 10 late failures. Previous glaucoma surgery was the only significant risk factor for failure (relative risk, 7.1; 95% confidence interval, 2.1-37.0). The 1-, 2-, and 3-year graft survival rates were 96%, 89%, and 89% without versus 78%, 53%, and 39% with previous glaucoma surgery. CONCLUSIONS: Treatment of failed PK with DMEK produced similar 4-year survival (76%) and better visual outcomes than previously reported with Descemet stripping endothelial keratoplasty or an initial PK regraft.

Micropulse Transscleral Cyclophotocoagulation in Keratoplasty Eyes.

PURPOSE: To assess the outcomes of micropulse transscleral cyclophotocoagulation for intraocular pressure (IOP) control in keratoplasty eyes. METHODS: Outcomes of micropulse laser treatments of postkeratoplasty eyes were retrospectively reviewed. IOP was assessed with applanation tonometry. Keratoplasty survival was calculated with Kaplan-Meier survival analysis. RESULTS: Sixty-one eyes in 57 patients received laser treatment; 31 eyes received 1, 21 received 2, 8 received 3, and 1 received 4 treatments. The median follow-up was 21 months (range, 2-35 months). At baseline, the mean IOP was 28 ± 11 mm Hg. At 1, 3, 6, and 12 months after the last treatment, respectively, the numbers of eyes with IOP data were 58, 50, 46, and 38; the mean IOP was 17 ± 7, 17 ± 8, 18 ± 9, and 15 ± 5 mm Hg; the proportions of eyes with IOP ≤ 15 mm Hg were 40%, 51%, 48%, and 55%; and the proportions with IOP ≤ 12 mm Hg were 21%, 29%, 20% and 29%. Six eyes (10%) received subsequent glaucoma filtration surgery. The mean number of antiglaucoma medications used before the initial treatment was 2.7 (range, 0-4) versus 2.2 (range, 0-4) at last follow-up. At baseline, 7 grafts were decompensated and 5 of 54 clear grafts (9%) had endothelial cell density < 700 cells/mm. Graft survival was 94% at 1 year and 81% at 2 years after the initial laser treatment. CONCLUSIONS: Micropulse transscleral cyclophotocoagulation is a noninvasive alternative to glaucoma filtration surgery for IOP reduction in keratoplasty eyes.

Patient satisfaction with epithelium-off corneal crosslinking.

PURPOSE: To assess patient satisfaction with corneal crosslinking (CXL). SETTING: Price Vision Group, Indianapolis, Indiana, USA. DESIGN: Prospective case series. METHODS: Patients treated with the Dresden protocol or accelerated epithelium-off CXL during an 8-year period were invited to participate in an electronic survey. RESULTS: Of the 552 patients who were invited to participate, 448 (80% response rate) completed the electronic survey. The median time from CXL to survey completion was 3.5 years (range 1 to 9 years). The participants were 73% men; 78% had keratoconus, 22% had post-refractive surgical ectasia, and 44% had bilateral treatment. Comparable proportions of those treated with standard and accelerated CXL reported that it halted disease progression (88% versus 87%, respectively, P = .78). A younger treatment age was associated with higher perceived efficacy (P = .0003). The proportion who considered CXL effective was 93% among those with mild keratoconus, 86% with moderate to severe keratoconus, and 78% with post-refractive surgical ectasia (P = .0004). Regarding vision, 41% reported improvement after CXL, 46% noted no change, and 14% perceived continued decline. The mean satisfaction score was 8.8 ± 1.7 (SD) on a scale of 1 (would not recommend CXL) to 10 (definitely would recommend) among those treated for keratoconus and 7.6 ± 2.5 among those treated for ectasia after keratorefractive surgery (P < .0001). Eleven (1.7%) of 644 treated eyes had subsequent keratoplasty. CONCLUSION: Most patients considered CXL effective. The perceived efficacy did not vary significantly as a function of follow-up time (P = .90), suggesting no discernible fading of effect over the 1- to 9-year follow-up.

Overview of Systemic Candida Infections in Hospital Settings and Report of Candida After DMEK Successfully Treated With Antifungals and Partial Graft Excision.

PURPOSE: To report novel surgical and medical management of intraocular and corneal infection with Candida glabrata that manifested 3 months after Descemet membrane endothelial keratoplasty (DMEK) and to review demographic reasons for increasing fungal contamination of donor tissue. METHODS: Demographics, donor rim cultures, diagnostic tests, management, clinical course, outcomes, and donor mate outcomes are reported for a fungal infection after DMEK. RESULTS: The fungal infection was treated for 3 weeks with a combination of intracameral and intracorneal voriconazole and intracameral and topical amphotericin B (off-label use). After initial improvement, the infection appeared to spread to the posterior chamber and the cornea decompensated. Pars plana vitrectomy was performed, and the fungal plaque and underlying area of the graft (approximately 3 mm area) were excised with the vitrector. After surgical intervention, the voriconazole and amphotericin B injections were discontinued, and oral posaconazole was prescribed for 2 months (off-label use). This combination of surgical and medical management successfully cleared the infection. Surprisingly, corneal edema completely resolved, and central DMEK endothelial cell density was 2506 cells/mm 1 month after discontinuing the antifungal injections, which apparently caused reversible endothelial toxicity. CONCLUSIONS: The incidence of nosocomial fungal infections, particularly non-albicans Candida, is increasing, as are the rates of positive fungal cultures from corneal donor tissue and postkeratoplasty fungal infections. Prospective studies are needed to assess the value of routine donor cultures, compare the safety and efficacy of various prophylactic treatments, and evaluate addition of antifungals to cold storage media.

Endothelium-in Versus Endothelium-out Insertion With Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To determine whether graft orientation during insertion affects Descemet membrane endothelial keratoplasty (DMEK) outcomes. METHODS: This was a retrospective analysis of 754 consecutive DMEK cases performed by 2 experienced surgeons to treat Fuchs dystrophy. Both surgeons used an intraocular lens insertor. One surgeon always inserted the tissue scrolled endothelium outward (group 1, n = 245). The other surgeon tested 3 methods: endothelium-outward scroll configuration (group 2, n = 161), endothelium-inward trifold configuration (group 3, n = 172), and trifold configuration with concurrent use of an anterior chamber maintainer (group 4, n = 176). The main outcome measures were rebubbling rate, regrafting or failure within 6 months, and 6-month endothelial cell loss. The tissue unfolding time from graft insertion to air fill was measured in a subset of 120 cases by 1 surgeon. RESULTS: The rebubbling rates were comparable across groups (ie, 12%, 10%, 10%, and 13% for groups 1, 2, 3, and 4, respectively, P = 0.21). The 6-month graft failure/replacement rates were comparable across groups (ie, 0.8%, 1.2%, 2.3%, and 0.6%, respectively, P = 0.18). Similarly, the 6-month endothelial cell loss did not differ significantly between groups (ie, 28% ± 11%, 30% ± 13%, 28% ± 15%, and 27% ± 13%, respectively, P = 0.019). In the subset analysis, the tissue unfolding time was similar for scroll and trifold configurations (6.0 ± 3.5 vs. 5.4 ± 3.0 minutes, respectively, P = 0.43). CONCLUSIONS: The outcomes were similar for endothelium-out and endothelium-in (trifold) insertion methods with DMEK, suggesting that the choice is a matter of surgeon preference.

Intraoperative hyphema in Descemet membrane endothelial keratoplasty alone or combined with phacoemulsification.

PURPOSE: To identify whether intraoperative hyphema from the peripheral iridotomy during Descemet membrane endothelial keratoplasty (DMEK) is associated with anticoagulant or antiplatelet use, age, combined phacoemulsification, or adverse outcomes. SETTING: Price Vision Group, Indianapolis, Indiana, USA. DESIGN: Retrospective case series. METHODS: Data were obtained from consecutive DMEK cases with an intraoperative iridotomy from July 2015 through July 2016. Hyphema was classified as negative or positive (small or large). Associations with possible risk factors and with transplant outcomes were assessed. RESULTS: Of 445 cases, 262 (59%) were negative for hyphema and 183 (41%) were positive. The proportion of patients who used preoperative anticoagulant or antiplatelet medication did not differ significantly with the hyphema classification (negative hyphema 42%, small hyphema 34%, large hyphema 46%) (P = .31). Likewise, recipient age was not a risk factor for hyphema (P = .085). Hyphema was more likely in cases combined with phacoemulsification than in single DMEK procedures (relative risk, 1.5 [95% confidence interval, 1.2-1.9]). Hyphema was not associated with postoperative rebubbling rates (negative hyphema 10.5%, small hyphema 10.3%, large hyphema 8.0%) (P = .33), 6-month endothelial cell loss (mean = 29%, P = .19), or 6-month visual acuity (mean = 20/25 Snellen in all hyphema groups, P = .98). CONCLUSIONS: Preoperative anticoagulant or antiplatelet use was not a significant risk factor for hyphema. The risk for hyphema was increased somewhat when DMEK was combined with cataract surgery. Intraoperative hyphema did not significantly affect the rebubbling rate, endothelial cell loss, or visual acuity outcomes.

Recurrence of Granular Corneal Dystrophy Type 1 After Phototherapeutic Keratectomy, Lamellar Keratoplasty, and Penetrating Keratoplasty in a Single Population.

PURPOSE: To describe the recurrence of granular corneal dystrophy type 1 (GCD1) after penetrating keratoplasty (PKP), anterior lamellar keratoplasty (ALK), deep anterior lamellar keratoplasty (DALK), and phototherapeutic keratectomy (PTK) in a single population. The time required to achieve best-corrected visual acuity (BCVA) after each intervention was also analyzed. METHODS: Retrospective review of all patients with GCD1 from a single center between 1989 and 2016. Surgical interventions were performed 50 times on 28 eyes of 15 patients. Data were primarily analyzed through Cox regression modeling with clustering and robust log-rank testing. RESULTS: Significant recurrence occurred most rapidly after PTK (median time 2.7 years) and was most delayed after PKP (13.7 years). Significant recurrence occurred at a similar interval after ALK and DALK (3.7 and 3.2 years, respectively). Significant recurrence-free survival was longer for PKP than for ALK, DALK, or PTK (P = 0.04). The time required to obtain BCVA was shorter in the PTK group (median 1.8 months) than in the PKP and DALK groups (median 5.3 and 8.4 months, respectively; P = 0.03 and P = 0.02). All groups achieved a similar median BCVA (20/25-20/30). CONCLUSIONS: This series indicates that GCD1 recurrence-free survival is longest after PKP with an associated delay in attaining BCVA. Conversely, PTK provided the fastest visual recovery with shorter recurrence-free survival.

Effect of Donor and Recipient Diabetes Status on Descemet Membrane Endothelial Keratoplasty Adherence and Survival.

PURPOSE: To evaluate whether donor and/or recipient diabetes status affects the outcomes of Descemet membrane endothelial keratoplasty (DMEK). METHODS: A consecutive, single-center DMEK case series was reviewed. The outcome measures were success of surgeon tissue preparation, air reinjection rate, Kaplan-Meier 4-year graft replacement/failure rate for any reason, and endothelial cell loss. RESULTS: The donor had a history of diabetes in 504 of 1791 cases (28%) and the recipient in 14%. For donors without and with diabetes, the preparation success rate was 99% versus 95% (P < 0.0001), the air reinjection rate was 16% versus 18% (P = 0.19), and the 4-year graft replacement/failure rate was 7% versus 9%, respectively (P = 0.15). Endothelial cell loss was not associated with donor diabetes (P = 0.76). For recipients without and with diabetes, the 4-year graft replacement/failure rate was 7% versus 9% (P = 0.68), and median endothelial cell loss increased from 27% versus 29% at 1 month to 42% versus 48% at 4 years, respectively (P = 0.02). Recipient use of insulin therapy was associated with poorer graft attachment and a higher air reinjection rate (P = 0.0023). CONCLUSIONS: Although donor diabetes was associated with a 5-fold increased risk of tissue preparation failure, it was not significantly associated with air reinjection, graft survival, or endothelial cell loss. This provides reassurance that tissue prepared successfully from donors with diabetes is safe to use for DMEK. Recipient diabetes was associated with increased endothelial cell loss; the potential effect on longer-term graft survival merits further study.

Immunologic Rejection Episodes After Deep Anterior Lamellar Keratoplasty: Incidence and Risk Factors.

PURPOSE: To assess the rejection episode rate after deep anterior lamellar keratoplasty (DALK) and to identify associated risk factors. METHODS: This retrospective review of 251 primary DALK procedures performed by 14 surgeons at a single center between February 2008 and November 2015 evaluated the rejection episode rate and associated risk factors using Kaplan-Meier survival and proportional hazards analyses, which took the length of follow-up into consideration. RESULTS: Transplant indications were keratoconus or ectasia after laser refractive surgery (n = 170, 68%), corneal opacity (n = 72, 28%), and other anterior corneal disease (n = 9, 4%). The median recipient age was 46 years. The overall rejection episode rate was 14% with 18-month median follow-up and a 7-week median postoperative corticosteroid duration. In univariate analysis, increased risk of rejection episodes was associated with younger recipient age [relative risk (RR): 2.1, 95% confidence interval (CI): 1.4-5.2], African American race (RR: 2.1, 95% CI: 1.1-4.1), and use of manual trephination (compared with the femtosecond laser) for the side-cut incisions (RR: 2.7, 95% CI: 1.4-5.2). In multivariate analysis, the combined effect of patient age and race (P = 0.0012) and the side-cut method (P = 0.021) were each significant risk factors. CONCLUSIONS: This study demonstrates the substantial rate of rejection episodes that can be induced by corneal stroma in DALK and suggests that postoperative topical corticosteroids should be continued longer than the study's 7-week median and that young African Americans need higher-dose, longer-duration topical corticosteroids. The association between the side-cut method and rejection risk merits further investigation.

Anatomical double-bundle anterior cruciate ligament reconstruction.

A careful review of the literature suggests that a significant number of patients undergoing anterior cruciate ligament (ACL) reconstruction have less than optimal results. Although overall outcomes of ACL reconstruction are favourable, there remains considerable room for improvement. Anatomically, the ACL consists of two major functional bundles, the anteromedial and the posterolateral bundle. Biomechanically, both bundles contribute significantly to the anterior and the rotational stability of the knee. Therefore, anatomical double-bundle ACL reconstruction techniques may further improve the outcomes in ACL surgery. Our preferred technique for arthroscopic double-bundle ACL reconstruction includes the use of two femoral and two tibial tunnels to restore both the anteromedial and the posterolateral bundle of the ACL and their anatomical footprints at their tibial and femoral insertion site. We use two tibialis anterior tendon allografts for the restoration of the two ACL bundles. Clinical long-term outcome studies may focus on the evaluation of functional outcomes, restoration of anterior and rotational knee stability, and the risk of degenerative osteoarthritis of the knee joint following anatomical double-bundle ACL reconstruction versus single-bundle ACL reconstruction.