Utilization rate and usage patterns of phakic and pseudophakic donor corneas recovered by the Singapore Eye Bank.

PURPOSE: To compare the utilization rate and usage patterns of pseudophakic and phakic donor corneas recovered by the Singapore Eye Bank. METHODS: Records of local donor corneas recovered by the Singapore Eye Bank from 2012 to 2017 were examined. Corneas that were deemed suitable for clinical use were stratified into phakic and pseudophakic groups. We examined the basic demographic pattern of both groups and the initial type of surgery/ies that the corneas were suitable for based on tissue parameters such as time from harvesting, stromal clarity, the clear central corneal area, the presence of Descemet's membrane tears or defects, and endothelial cell density and quality. We also identified the types of corneal grafts that the corneas were eventually used for; Penetrating Keratoplasty (PK), Anterior Lamellar Keratoplasty (ALK), Endothelial Keratoplasty (EK). Finally, the overall utilization rates for each group were determined. RESULTS: A total of 986 corneas deemed suitable for transplant were analyzed, 908 (92%) were phakic and 78 were pseudophakic (8%). The average age of pseudophakic donor corneas was (65 ± 8 yrs. old) and there was a slight male preponderance for both groups (55%). Age adjusted analysis of pseudophakic corneas showed the endothelial cell density (ECD) (mean: 2327 ± 47.1 cells/mm2) and clear area (mean: 7.0 ± 0.7 mm) were lesser than phakic corneas. The percentage of pseudophakic corneas that were of EK standard (ECD >2500 cells/mm2) were lower compared to phakic corneas (37% and 77% respectively, p < 0.001). There was significant correlation between previous cataract surgery and the endothelial cell count of the donor corneas (p < 0.001), and regression analysis also showed a strong association of ECD with cataract surgery in reference to non-cataract surgery (-478.8 (95% CI-576.9 to -380.7). The overall utilization rate for pseudophakic corneas was 58% compared to that of phakic corneas at 83%. The most common reason for pseudophakic corneas not to be utilized was due to the presence of Descemet's membrane (DM) tears or defects under the main or side port incision created during phacoemulsification (30%). Phakic corneas were used primarily for optical grafts 84% (mainly EK) while pseudophakic corneas were used mostly for therapeutic/tectonic grafts 47% (mainly ALK or patch grafts). CONCLUSION: Compared to phakic donor corneas, pseudophakic corneas generally have lower overall tissue quality leading to lower uptake by surgeons and lower utilization rates. Eye banks must continuously refine their donor acceptance criteria and engage surgeons to optimize utilization of each recovered tissue.

Long-Term Review of Penetrating Keratoplasty: A 20-Year Review in Asian Eyes.

PURPOSE: To review the long-term outcomes of optical, therapeutic and tectonic forms of penetrating keratoplasty over a 20-year period in Asian eyes. DESIGN: Prospective cohort study involving the Singapore Corneal Transplant Study (SCTS). METHODS: All penetrating keratoplasties (PK) performed at the Singapore National Eye Centre (SNEC) from January 1991 to December 2010 were analyzed using records from the computerized database of the SCTS. This database includes preoperative, intraoperative, and postoperative patient data and donor cornea data. Only primary grafts were included. Patient demographics, donor cornea source, indications for grafting, complications, graft survival rate, and causes of graft failure were analyzed. RESULTS: A total of 1,206 primary PKs were performed. The mean age of the patients was 55 years (range: <1-101 years). The overall corneal graft survival rates at 1, 5, 10, 15, and 20 years were 91%, 66.8%, 55.4%, 52%, and 44%, respectively. For optical grafts, pseudophakic bullous keratopathy, postinfectious corneal scarring and thinning and keratoconus were the most common diagnoses. Graft survival for optical grafts was significantly better than therapeutic and tectonic grafts at all time points. Multivariate analysis suggested that a younger donor cornea age and higher donor endothelial cell count are associated with better long-term graft survival for optical grafts. Irreversible allograft rejection and late endothelial failure accounted for more than 60% of graft failures. CONCLUSIONS: Graft survival decreased over time from 91% at 1 year to 44% at 20 years' follow-up. Allograft rejection and late endothelial failure accounted for more than 60% of graft failures.

Interventions for the management of CMV-associated anterior segment inflammation.

BACKGROUND: Cytomegalovirus (CMV) is a virus that usually affects people with reduced immunity. In recent years, this virus has been thought to cause repeated inflammation in the eye, in otherwise healthy people. This form of inflammation can cause damage to the cornea (the outer layer of the eye) or to the optic nerve by causing secondary glaucoma, or to both, leading to visual loss. OBJECTIVES: Our primary objective was to assess the effects of drug therapies for the treatment of CMV-associated anterior segment inflammation.Our secondary objective was to determine the optimal dose and duration of treatment with respect to recurrence and adverse effects. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 21 March 2017), Embase Ovid (1947 to 21 March 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 21 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 21 March 2017, and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 21 March 2017. We did not use any date or language restrictions in the electronic searches for trials. Two review authors independently reviewed the titles and abstracts. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) on the management of CMV-associated anterior segment inflammation. DATA COLLECTION AND ANALYSIS: We planned to have two review authors independently extract data from reports of included studies and analyse data based on methods expected by Cochrane. MAIN RESULTS: We did not identify any RCTs that met our inclusion criteria. AUTHORS' CONCLUSIONS: There is currently no good-quality evidence on the management of CMV-associated anterior segment inflammation. Ideally, a well-designed RCT is needed to evaluate the effectiveness of different anti-CMV medications as well as the optimal dose and duration.

Histological features of Cytomegalovirus-related corneal graft infections, its associated features and clinical significance.

AIM: To describe the histological features of ITALIC! Cytomegalovirus (CMV)-related corneal graft infections, its associated features and clinical significance. METHODS: This was a retrospective histological study of 48 consecutive cases of failed repeat penetrating keratoplasty cases with a clinical diagnosis of allograft rejection from 2011 to 2013. CMV infection was confirmed with CMV antibody immunohistochemistry (IHC) and electron microscopy. Additional CD163 and CD68 IHCs for macrophages were also performed. Clinical data and previous graft histology were then reviewed. RESULTS: Mean incidence of CMV infection in corneal graft rejection buttons was 6.3% per year. 3/48 graft buttons were CMV antibody positive. Histological features of CMV graft infection include: (1) stromal keratocytes with cytopathic changes; (2) lack of inflammation, only occasional macrophages present and (3) absence of vascularisation. None of the patients had a history of active CMV infection. CONCLUSION: CMV infection is not limited as endotheliitis, but extends into the corneal stroma, and is a potential reservoir for graft infection, especially in partial thickness endothelial surgery. Clinical features are often non-specific, although glaucoma was present in our patients. CMV-infected grafts showed CD163-positive M2 macrophages in close association with the infected keratocytes, suggesting that the macrophage may be important in CMV graft infection. Histological examination with CMV IHC is a useful method to detect CMV infection postoperatively. Post penetrating keratoplasty, CMV systemic treatment with valganciclovir can prevent graft infection and failure. Boston keratoprosthesis may be a potential alternative surgery in active CMV infections that obviates the need for systemic therapy.

The outcomes of primary pediatric keratoplasty in Singapore.

PURPOSE: To evaluate the long-term corneal graft survival and risk factors for graft failure in pediatric eyes. DESIGN: Retrospective, interventional consecutive case series. METHODS: Unilateral eyes of 105 patients aged 16 years and below were included from the Singapore Corneal Transplant Study between April 4, 1991 and April 4, 2011. Corneal graft survival was calculated using Kaplan-Meier survival analysis, and survival distributions were compared using log-rank test. RESULTS: Mean recipient age was 8.38 ± 5.63 years (range 0.18-15.92 years). Mean follow-up time was 34.16 ± 39.10 months. Main diagnoses were corneal scar (22.9%), limbal dermoid (21.9%), anterior segment dysgenesis (15.2%), and keratoconus (14.3%). Forty-four eyes (41.9%) underwent penetrating keratoplasty (PK), 37 (35.2%) underwent anterior lamellar keratoplasty (ALK), 22 (21.0%) underwent lamellar corneal patch graft, and 2 (1.9%) underwent Descemet stripping automated endothelial keratoplasty (DSAEK). Kaplan-Meier survival rates for PK were 92.8% at 1 year, 88.9% at 2-4 years, and 80.9% at 5-16 years; survival rates for ALK were 88.0% at 1 year and 84.3% at 2-7 years; survival rates for corneal patch graft were 100% at 1-3 years and 90% at 4-10 years; these were not statistically significant (P = .362). Deep corneal vascularization (P = .012), preexisting active inflammation (P = .023), preexisting glaucoma drainage device (P = .023), and preexisting ocular surface disease (P = .037) were associated with reduced graft survival in a univariate analysis. CONCLUSIONS: We report good long-term graft survival following pediatric keratoplasty for various indications. Lamellar keratoplasty, when indicated, should be the procedure of choice in high-risk keratoplasties.

Descemet stripping automated endothelial keratoplasty for Fuchs endothelial dystrophy-influence of graft diameter on endothelial cell loss.

PURPOSE: To evaluate the potential influence of graft diameter on endothelial cell loss after Descemet stripping automated endothelial keratoplasty. METHODS: A retrospective interventional case series of eyes treated with Descemet stripping automated endothelial keratoplasty for Fuchs endothelial dystrophy (n = 695) with at least 1-year follow-up at Price Vision Group (Indianapolis, IN) was analyzed, excluding eyes with prior glaucoma surgery. Graft diameters ranged from 7.5 to 9.5 mm, with 8.5- and 9-mm grafts accounting for the majority. Endothelial cell loss was assessed as a function of graft diameter by analysis of variance. RESULTS: Mean baseline donor endothelial cell density was 3039 cells per mm for 8.5-mm grafts (n = 225) and 3026 cells per mm for 9-mm grafts (n = 409). Mean endothelial cell density and postoperative endothelial cell loss at 1, 2, 3, 4, and 5 years was 2070 (32%), 1999 (34%), 1920 (37%), 1865 (39%), and 1617 (47%) cells per mm for 8.5-mm grafts versus 2098 (30%), 2019 (33%), 1857 (38%), 1854 (38%), and 1619 (46%) cells per mm for 9.0-mm grafts, respectively. Differences were not statistically significant at any time point. The rates of graft dislocation and immunologic rejection episode were comparable for 8.5-mm and 9.0-mm grafts (both P > 0.05). CONCLUSIONS: A larger graft diameter (9 mm) theoretically provides a larger reservoir of healthy endothelial cells but did not result in significantly less cell loss than a smaller diameter (8.5 mm) in eyes with Fuchs endothelial dystrophy during the 5-year follow-up.

Descemet membrane endothelial keratoplasty and hybrid techniques for managing failed penetrating grafts.

PURPOSE: To report the outcomes of Descemet membrane endothelial keratoplasty (DMEK) and Descemet membrane automated endothelial keratoplasty (DMAEK) for failed penetrating keratoplasties (PKs). METHODS: Retrospective chart review of patients with a failed PK who were managed with DMEK or DMAEK surgery. Surgical technique, clinical findings, visual outcomes, and complications were documented and reported. RESULTS: Six patients (mean age, 62 years; mean follow-up, 10 months) underwent DMEK (4 patients) or DMAEK (2 patients) under a failed PK. The graft diameter of the failed PK was 8 mm in all patients. In 3 patients, a 9-mm donor graft (DMAEK, 2; DMEK, 1) was used, whereas in the remaining patients, an 8-mm donor graft was chosen. Descemet membrane was stripped in 3 eyes because of the presence of Descemetic scarring. Four of the 6 eyes had a triple procedure. Two patients had preexisting open-angle glaucoma, whereas 1 patient developed postoperative steroid-response glaucoma. The median preoperative best-corrected visual acuity was 20/70, and postoperatively at 1, 3, and 6 months, 20/50, 20/40, and 20/30, respectively. The median donor endothelial cell density was 2801 cells per square millimeter, and at 3 and 6 months postoperatively, 1906 and 1880 cells per square millimeter, respectively. Three of the 4 DMEK eyes had peripheral graft detachment that attached successfully with 1 air injection. There was 1 primary failure that was managed with Descemet stripping endothelial keratoplasty. CONCLUSIONS: DMEK or DMAEK can be considered to treat failed PKs. However, prior experience in performing these techniques in virgin eyes is recommended before use with a failed PK, which can present an additional challenge.

A cause of reticular interface haze and its management after descemet stripping endothelial keratoplasty.

PURPOSE: To describe a cause and management of interface haze after Descemet stripping endothelial keratoplasty (DSEK). METHODS: Five patients underwent uncomplicated combined DSEK/phacoemulsification with intraocular lens implantation at a tertiary referral center over a span of 3 months. In each case, the recipient Descemet membrane was stripped with the anterior chamber filled with a cohesive viscoelastic. Patients subsequently developed visually significant haze in the graft-host interface that had a fine reticular pattern. Examination also revealed a small separation between the donor and recipient cornea in 3 cases. In all cases, there was no communication between the area of detachment and the anterior chamber, and the overlying recipient cornea was clear. Clinical and imaging findings of the interface haze suggested that it was the result of retained viscoelastic in the interface. Patients were either observed or underwent surgery to irrigate the viscoelastic from the interface. RESULTS: Of the 5 patients, 3 were simply observed with eventual clearing of the haze and attainment of best-corrected visual acuity of 20/40 or better. Two patients with more extensive interface haze and visible space on slit examination between the donor and recipient cornea underwent irrigation and aspiration of the graft-host interface, with quick resolution of the haze. All grafts remained clear at the last follow-up. CONCLUSIONS: Retained viscoelastic at the graft-host interface during DSEK can cause a reticular interface haze that can compromise visual clarity. The haze can be eliminated by irrigating and aspirating the graft-host interface with improvement in vision. Careful irrigation and aspiration of viscoelastic from the posterior corneal surface of the recipient at the time of endothelial keratoplasty can prevent this form of interface haze.

Descemet's stripping endothelial keratoplasty: long-term graft survival and risk factors for failure in eyes with preexisting glaucoma.

PURPOSE: To evaluate long-term corneal graft survival and risk factors for graft failure after Descemet's stripping endothelial keratoplasty (DSEK) in eyes with preexisting glaucoma. DESIGN: Retrospective case control study. PARTICIPANTS: A total of 835 DSEK cases performed by a single surgeon between December 2003 and August 2007 were reviewed. Only the first treated eye of each patient with at least 1 year follow-up was included, resulting in 453 cases; 342 had no prior glaucoma (C), 65 had medically managed preexisting glaucoma (G), and 46 had prior glaucoma surgery (GS). METHODS: Corneal graft failure was defined as persistent corneal edema resulting in irreversible loss of optical clarity. Corneal graft survival in the 3 groups was calculated using Kaplan-Meier survival analysis. Nine potential risk factors for graft failure were evaluated by Cox proportional hazards univariate and multivariate analysis. These methods took length of follow-up into consideration. MAIN OUTCOME MEASURES: Corneal graft survival and risk factors influencing long-term corneal endothelial failure. RESULTS: The 1-, 2-, 3-, 4-, and 5-year graft survival was 99%, 99%, 97%, 97%, and 96%, respectively, in group C; 100%, 98%, 98%, 96%, and 90%, respectively, in group G; and 96%, 91%, 84%, 69%, and 48%, respectively, in group GS (P < 0.001). In the GS group, the 5-year survival rate for eyes with a glaucoma drainage device (GDD) and those with trabeculectomy only was 25% and 59%, respectively. Indication for DSEK, surgically managed glaucoma, type and number of prior glaucoma surgeries, and occurrence of a rejection episode were the significant risk factors for graft survival in univariate analysis. Several factors were correlated; in a multivariate model, prior glaucoma surgery (P < 0.0001) and a prior rejection episode (0.0023) were the significant risk factors for corneal endothelial failure. CONCLUSIONS: Patients with medically managed glaucoma had significantly better 5-year graft survival than those with surgically managed glaucoma. A prior glaucoma shunt or trabeculectomy significantly increased the risk of DSEK endothelial failure.

Endothelial keratoplasty: a revolution in evolution.

Endothelial keratoplasty (EK) is continually evolving both in surgical technique and clinical outcomes. Descemet's stripping endothelial keratoplasty (DSEK) has replaced penetrating keratoplasty (PK) as the treatment of choice for corneal endothelial dysfunction. It is safe and predictable and offers early visual rehabilitation. Newer iterations include Descemet's membrane endothelial keratoplasty, Descemet's membrane automated endothelial keratoplasty, and other hybrid techniques. Early data on these newer EK techniques suggests that they provide significantly better visual outcomes compared to DSEK. Initial 5-year survival data indicates that EK is at least comparable to PK, and more widespread survival data is anticipated. Further work is needed to simultaneously optimize visual outcomes, refractive predictability, and endothelial cell survival, as well as surgical techniques of donor preparation and insertion.

Endothelial cell counts after Descemet's stripping automated endothelial keratoplasty versus penetrating keratoplasty in Asian eyes.

BACKGROUND: The purpose of this study was to compare endothelial cell counts after Descemet's stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty in Asian eyes. METHODS: This was a retrospective study of patients from our prospective Singapore Corneal Transplant Study cohort who received corneal transplantation in 2006-2008. We compared eyes that underwent DSAEK or penetrating keratoplasty for Fuchs' endothelial dystrophy or pseudophakic and aphakic bullous keratopathy. Clinical data, and donor and recipient characteristics were recorded. Of 241 patients who met our inclusion criteria, 68 underwent DSAEK and 173 underwent penetrating keratoplasty. The main outcome measure was endothelial cell loss at 1 year. Secondary outcome measures were graft survival and visual outcomes at 1-year follow-up. RESULTS: There were no significant differences in baseline characteristics of patients between the treatment groups. Percent endothelial cell loss at 1-year follow-up was greater in penetrating keratoplasty eyes (40.9% ± 2.9%) compared with DSAEK eyes (22.4% ± 2.3%; P < 0.001). DSAEK-treated eyes had significantly superior uncorrected visual acuity (mean difference = 0.42 ± 0.0059; P < 0.001) and best spectacle-corrected visual acuity (mean difference = 0.14 ± 0.032; P < 0.001) as compared with penetrating keratoplasty-treated eyes. Penetrating keratoplasty-treated eyes had worse astigmatism as compared with DSAEK-treated eyes (-3.0 ± 2.1 versus -1.7 ± 0.8; P < 0.001). Graft survival at 1 year was comparable in both groups, ie, 66/68 (97.0%) DSAEK-treated eyes versus 158/173 (92.0%) of penetrating keratoplasty-treated eyes had clear grafts (P = 0.479). CONCLUSION: We report lower percent endothelial cell loss comparing DSAEK and penetrating keratoplasty at 1-year follow-up in Asian eyes, with comparable graft survival rates in both groups.

Risk of corneal transplant rejection significantly reduced with Descemet's membrane endothelial keratoplasty.

PURPOSE: To evaluate the relative risk of immunologic rejection episode in patients who underwent Descemet's membrane endothelial keratoplasty (DMEK), Descemet's stripping endothelial keratoplasty (DSEK), and penetrating keratoplasty (PK). DESIGN: Comparative case series. PARTICIPANTS: One hundred forty-one eyes treated with DMEK at Price Vision Group, Indianapolis, Indiana. METHODS: The patients in the DMEK group were compared retrospectively with cohorts of DSEK (n = 598) and PK (n = 30) patients treated at the same center, with similar demographics, follow-up duration, and indications for surgery. The postoperative steroid regimen and rejection criteria were identical in the 3 groups. Kaplan-Meier survival analysis, which takes varying length of follow-up into consideration, was performed to determine the cumulative probability of a rejection episode 1 and 2 years after surgery. Proportional hazards analysis was used to determine the relative risk of rejection episodes between the 3 groups. P<0.05 was considered significant and calculated using the log-rank test. MAIN OUTCOME MEASURES: Rejection-free survival and cumulative probability of a rejection episode. RESULTS: The mean recipient age was 66 years (56% females and 94% Caucasian) and median follow-up duration was 13 months (range, 3-40) in the DMEK group. Fuchs' dystrophy was the most common indication for surgery (n = 127; 90%) followed by pseudophakic bullous keratopathy (n = 4; 4%) and regrafts (n = 9; 6.4%). Only 1 patient (0.7%) had a documented rejection episode in the DMEK group compared with 54 (9%) in the DSEK and 5 (17%) in the PK group. The Kaplan-Meier cumulative probability of a rejection episode at 1 and 2 years was 1% and 1%, respectively, for DMEK; 8% and 12%, respectively, for DSEK; and 14% and 18%, respectively, for PK. This was a highly significant difference (P = 0.004). The DMEK eyes had a 15 times lesser risk of experiencing a rejection episode than DSEK eyes (95% confidence limit [CL], 2.0-111; P = 0.008) and 20 times lower risk than PK eyes (95% CL, 2.4-166; P = 0.006). CONCLUSIONS: Patients undergoing DMEK had a significantly reduced risk of experiencing a rejection episode within 2 years after surgery compared with DSEK and PK performed for similar indications using the same corticosteroid regimen.

Endothelial keratoplasty: fellow eyes comparison of Descemet stripping automated endothelial keratoplasty and Descemet membrane endothelial keratoplasty.

PURPOSE: To evaluate patients' perspectives and outcomes of 2 different endothelial keratoplasty (EK) techniques performed in the fellow eyes of the same patients: Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK). METHODS: In this fellow eye, comparative, retrospective case series, the records of 15 patients who underwent DSAEK in 1 eye and DMEK in the fellow eye and completed at least 1 year of follow-up after the second procedure were reviewed. Visual outcomes and endothelial cell density were assessed. Patient satisfaction was evaluated using a subjective questionnaire. RESULTS: At 12 months postoperatively, the mean best spectacle-corrected visual acuity (BSCVA) in the DMEK group was 0.07 logarithm of the minimum angle of resolution (20/24) and 0.20 logMAR (20/32) in the DSAEK group (P = 0.004). The majority of the patients (85%) perceived better visual quality in the DMEK eye. Furthermore, 62% preferred or would recommend DMEK to a friend or relative, whereas 15% preferred DSAEK and 23% reported no preference between the surgical procedures. The 1-year endothelial cell loss and the perceived discomfort level during the postoperative period were comparable for the 2 procedures. CONCLUSIONS: The majority of the patients preferred or would recommend the DMEK procedure. Faster visual recovery and better final visual acuity were the main benefits of the DMEK technique.

Descemet's stripping endothelial keratoplasty under failed penetrating keratoplasty: visual rehabilitation and graft survival rate.

PURPOSE: To evaluate graft survival, risk factors for failure, complications, and visual rehabilitation in patients who underwent Descemet's stripping endothelial keratoplasty (DSEK) under a failed penetrating keratoplasty (PK). DESIGN: Retrospective interventional case series. PARTICIPANTS: Sixty eyes (60 patients) treated at Price Vision Group, Indianapolis, Indiana. METHODS: Graft diameters ranged from 8 to 9 mm and were ∼1 mm larger than the previous PK. The Descemet's membrane was not stripped in the majority (54, 84%). The graft was inserted using forceps or a Busin funnel glide (Moria, Anthony, France). The probability of graft survival was calculated by Kaplan-Meier survival analysis. MAIN OUTCOME MEASURES: Graft survival, best-corrected visual acuity (BCVA), and complications. RESULTS: The mean recipient age was 68 years (range, 17-95 years). Forty eyes had 1 previous failed PK, 14 eyes had 2 previous failed PKs, and 6 eyes had 3 previous failed PKs. Thirty-one eyes (52%) had preexisting glaucoma, and 16 eyes (27%) had prior glaucoma surgery (trabeculectomy in 4, shunt procedure in 12). Fifty-five grafts were performed for visual rehabilitation, and 5 grafts were performed for pain relief. Median follow-up was 2.3 years (range, 2 months to 6 years). Median preoperative BCVA was 1.23 logarithm of the minimum angle of resolution (logMAR) (range, 0.2-3, Snellen 20/340), and median postoperative visual improvement was 0.6 logMAR (6 lines), range -0.3 to +2.7. Four eyes had graft detachment (6.6%), 7 eyes (10.5%) had endothelial rejection, and 10 eyes (16.6%) had graft failure (primary failure in 2, secondary failure in 8). The overall secondary graft survival rates were 98%, 90%, 81%, and 74% at 1, 2, 3, and 4 years, respectively. Prior glaucoma shunt was the principal risk factor for graft failure. The graft survival rates were 100%, 96%, 96%, and 96% in eyes without a prior shunt versus 93%, 74%, 44%, and 22% with a prior shunt at 1, 2, 3, and 4 years, respectively (P=0.0005; relative risk = 20). Peripheral anterior synechiae (P=0.14), neovascularization (P=0.88), endothelial rejection (P=0.59), and number of prior PKs (P=0.13) were not independent risk factors for graft failure. CONCLUSIONS: Endothelial keratoplasty under a previous failed PK is a useful alternative to a repeat standard PK, particularly in eyes with an acceptable topography and refractive outcome before failure. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Descemet's membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss.

PURPOSE: To report 1-year outcomes of Descemet's membrane endothelial keratoplasty (DMEK) performed at 2 centers. DESIGN: Prospective, consecutive, interventional series. PARTICIPANTS: Patients with Fuchs' endothelial dystrophy, pseudophakic bullous keratoplasty, or failed previous graft (n = 136 eyes). INTERVENTION: The diseased central 7 mm of Descemet's membrane (DM) was stripped from the recipient cornea and replaced with healthy DM and endothelium stripped from donor corneas through a 2.8-mm corneal incision. Descemet's membrane endothelial keratoplasty was performed alone (n = 110) or combined with either phacoemulsification and intraocular lens implantation (n = 23) or pars plana vitrectomy (n = 3). MAIN OUTCOME MEASURES: Best spectacle-corrected visual acuity (BSCVA), manifest refraction, and endothelial cell density. RESULTS: Excluding eyes with pre-existing ocular comorbidities or those lost to follow-up, mean BSCVA at 1 year was 0.07 logarithm minimum angle of resolution (logMAR) units (20/24; range, 20/15-20/40; n = 81), improving from 0.51 logMAR (20/65; range, 20/20-counting fingers); 41% of the patients achieved a BSCVA of 20/20 or better, 80% could be corrected to 20/25 or better, and 98% achieved 20/30 or better vision. A refractive hyperopic shift of +0.24 ± 1.01 diopters (D; range, -1.50 to 2.25 D) was found at 1 year, but it was not statistically significant (P = 0.08). Also, there was no significant change in the preoperative astigmatism (P = 0.17). The endothelial cell loss at 1 year was 36 ± 20% (n = 94; range, 13%-88%), with most of the loss being observed during the first 3 months after surgery: 31 ± 18% (range, 3%-77%). The DMEK graft creation could not be successfully completed in 6 cases (4.2%). All these unsuccessful attempts were among the initial 40 cases. Intracameral air was used to fix graft detachments, which usually were partial and peripheral, in 62% of the cases. Eleven grafts (8%) demonstrated primary failure and 1 eye (0.7%) had secondary failure resulting from endothelial rejection. Episodes of immunologic rejection were documented in 7 eyes (5.1%) during the first year of follow-up. CONCLUSIONS: Descemet's membrane endothelial keratoplasty had better visual acuity results in the first year after surgery than typically reported for other endothelial keratoplasty techniques, such as Descemet's stripping automated endothelial keratoplasty, while having less refractive changes and similar endothelial cell counts but a higher rebubbling rate. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Alterations in the aqueous humor proteome in patients with a glaucoma shunt device.

PURPOSE: To investigate whether implantation of a glaucoma shunt device leads to inappropriate accumulation of plasma derived proteins in the aqueous humor. METHODS: Aqueous humor samples were collected from 11 patients (study group) with a glaucoma shunt device undergoing either cataract surgery or a corneal transplant and 11 patients (control) with senile cataract undergoing routine cataract extraction. Of the study group, 9 had an Ahmed valve implant and 2 eyes had a Baerveldt implant. Tryptic digests of the mixture of proteins in aqueous humor (AH) were analyzed using Liquid Chromatography/Mass Spectrometry (LC-MS/MS). Proteins were identified with high confidence using stringent criteria and compared quantitatively using a label-free platform (IdentiQuantXL™). RESULTS: We identified 135 proteins in the albumin-depleted fraction in both the study and control group AH. Using stringent criteria, 13 proteins were detected at a significantly higher level compared to controls. These proteins are known to play a role in oxidative stress, apoptosis, inflammation and/or immunity and include gelsolin (p=0.00005), plasminogen (p=0.00009), angiotensinogen (p=0.0001), apolipoprotein A-II (p=0.0002), beta-2-microglobulin (p=0.0002), dickkopf-3 (DKK-3; p=0.0002), pigment epithelium-derived factor (p=0.0002), RIG-like 7-1 (p=0.0002), afamin (p=0.0003), fibronectin 1 (FN1; p=0.0003), apolipoprotein A-I (p=0.0004), activated complement C4 protein (C4a; p=0.0004) and prothrombin (p=0.0004). Many of the identified proteins were novel proteins that have not been associated with glaucoma in prior studies. All but C4a (complement C4 is a plasma protein but not in an activated form) are known plasma proteins and the elevated levels of these proteins in the aqueous humor suggests a breach in the blood-aqueous barrier with passive influx into the anterior chamber of the eye. CONCLUSIONS: The presence of these proteins in the aqueous humor suggests that glaucoma shunt device causes either a breach in blood-aqueous barrier or chronic trauma, increasing influx of oxidative, apoptotic and inflammatory proteins that could potentially cause corneal endothelial damage.

Postoperative risk factors influencing corneal graft survival in the Singapore Corneal Transplant Study.

PURPOSE: To determine postoperative risk factors that influence long-term corneal graft survival. DESIGN: Prospective cohort study. METHODS: Nine-hundred one consecutive penetrating keratoplasty procedures for optical, therapeutic, or tectonic indications from the Singapore Corneal Transplant Study. Univariate and multivariate analysis was performed for postoperative risk factors; Cox proportional hazards regression with a time-dependent covariate was used for preoperative, intraoperative, donor, and postoperative risk factors in a combined model. RESULTS: Raised intraocular pressure (20.7%) was the most common complication, followed by rejection (18.2%), whereas glaucoma surgery (7.9%) and repeat grafting (7.3%) were the most common procedures after penetrating keratoplasty. The primary graft failure rate was 1.4%, and late failure was seen in 9.4% of eyes. In the combined regression model, rejection (hazard ratio [HR], 3.4; P = .00), microbial keratitis (HR, 3.6; P = .00), endophthalmitis (HR, 7.7; P = .00), primary disease recurrence (HR, 73.9; P = .00), wound dehiscence (HR, 2.8; P = .02), lid surgery (HR, 2.3; P = .02), glaucoma surgery (HR, 2.46; P = .02), and repeat grafting (HR, 3.2; P = .00) were the significant postoperative failure predictors; the significant preoperative and intraoperative factors identified were female gender, graft size of less than 7 mm and more than 9 mm, primary diagnosis, preoperative inflammation, and preexisting perforation. CONCLUSIONS: Postoperative complications and operative procedures after grafting have an adverse effect on graft survival.

Anterior lamellar keratoplasty: 'Back to the Future'- a review.

Newer forms of lamellar keratoplasty techniques have emerged in the last decade or so revolving around the concept of targeted replacement of diseased corneal layers. These include anterior lamellar keratoplasty (ALK) techniques that aim to selectively replace diseased corneal stroma and, endothelial keratoplasty techniques aiming to replaced damaged endothelium in endothelial disorders. ALK surgery has a distinct advantage over penetrating keratoplasty (PK) in that it minimizes unnecessary replacement of the unaffected healthy endothelial layer thereby almost eliminating the risk of endothelial rejection, a major cause of graft failure in PK. Overall it provides increased life expectancy to the graft and with advancements in the surgical technique and instrumentation for ALK, the visual outcomes are now comparable if not better to standard PK. There are several forms of ALK procedures that have evolved to cater to a wide range of stromal disorders. This article reviews the various emerging techniques of anterior lamellar surgery, its indications and visual outcomes, to emphasize the shift from PK to ALK for stromal disorders with a healthy endothelium.

Paradigm shifts in corneal transplantation.

Conventional corneal transplantation, in the form of penetrating keratoplasty (PK), involves full-thickness replacement of the cornea, and is a highly successful procedure. However, the cornea is anatomically a multi-layered structure. Pathology may only affect individual layers of the cornea, hence selective lamellar surgical replacement of only the diseased corneal layers whilst retaining unaffected layers represents a new paradigm shift in the field. Recent advancements in surgical techniques and instrumentation have resulted in several forms of manual, microkeratome and femto-second laser-assisted lamellar transplantation procedures. Anterior lamellar keratoplasty (ALK) aims at replacing only diseased or scarred corneal stroma, whilst retaining the unaffected corneal endothelial layer, thus obviating the risk of endothelial allograft rejection. Posterior lamellar keratoplasty/endothelial keratoplasty (PLK/EK) involves the replacement of the dysfunctional endothelial cell layer only. Whilst significant technical and surgical challenges are involved in performing lamellar micro-dissection of a tissue which is only 0.5 mm thick, the benefits of a more controlled surgical procedure and improved graft survival rates have resulted in a shift away from conventional PK. This review details the current advances in emerging lamellar corneal surgical procedures and highlights the main advantages and disadvantages of these new lamellar corneal procedures.

Cytomegalovirus endotheliitis in Descemet's stripping endothelial keratoplasty.

OBJECTIVE: To report 4 cases of undiagnosed cytomegalovirus (CMV) endotheliitis in patients who underwent Descemet's stripping automated endothelial keratoplasty (DSAEK). DESIGN: Retrospective interventional case series. PARTICIPANTS: Four eyes of 4 patients diagnosed with active CMV endotheliitis after DSAEK. METHODS: Retrospective review of the medical records of 4 patients with DSAEK who had an aqueous tap that was positive for CMV DNA but negative for herpes simplex virus (HSV) and varicella zoster virus. MAIN OUTCOME MEASURE: Clinical features and management. RESULTS: Four immunocompetent Chinese male patients with a mean age of 67 years underwent DSAEK for posterior polymorphous dystrophy (1), Fuchs' heterochromic cyclitis (1), pseudophakic bullous keratopathy (1), and herpetic keratouveitis (1). Clinical findings seen in all patients were localized corneal edema, increased intraocular pressure, pigmented keratic precipitates (KPs), and no/minimal anterior chamber (AC) activity. An unexplained sudden decrease in endothelial cell count (ECC) in the absence of rejection or significant inflammation was seen in 3 patients, whereas 1 patient also developed concomitant retinitis. CMV DNA was positive in all aqueous specimens and from the vitreous of the patient with retinitis. All patients were treated with oral valganciclovir with resolution of inflammation; 2 patients had recurrences; 1 patient developed recurrent retinitis; and 1 patient developed recurrent CMV endotheliitis and is currently receiving maintenance therapy with oral valganciclovir. CONCLUSIONS: CMV endotheliitis with corneal edema masqueraded as a variety of other endothelial conditions, which resulted in DSAEK surgery being performed in these patients who may have responded to antiviral treatment without the need for endothelial transplantation. A heightened awareness is required to exclude CMV endotheliitis as the cause for endothelial decompensation or unexplained, sudden reduction in ECCs post-DSAEK in the absence of other complications, and it should be differentiated from allograft rejection in view of the critical difference in treatment.