A Randomized Multicenter Clinical Trial of Ultrathin Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) versus DSAEK.

OBJECTIVE: To compare visual acuity, refraction, endothelial cell density (ECD), and complications after Descemet stripping automated endothelial keratoplasty (DSAEK) and ultrathin DSAEK (UT-DSAEK). DESIGN: A multicenter, prospective, double-masked, randomized, controlled clinical trial. PARTICIPANTS: From 66 patients with irreversible corneal endothelial dysfunction dues to Fuchs' dystrophy who enrolled from 4 tertiary medical centers in the Netherlands, 66 eyes were studied. METHODS: Participants were centrally randomized to undergo either UT-DSAEK or DSAEK, based on preoperative best spectacle-corrected visual acuity (BSCVA), recipient central corneal thickness, patient age, and recruitment center. Donor corneas were precut by a single cornea bank. PARTICIPANTS: Participants underwent ophthalmic examinations preoperatively and 3, 6, and 12 months after the operation, including manifest refraction, BSCVA using an Early Treatment Diabetic Retinopathy Study chart, and endothelium imaging. MAIN OUTCOME MEASURES: BSCVA 12 months postoperatively. RESULTS: Preoperative BSCVA did not differ between patients undergoing DSAEK (0.35 logarithm of the minimum angle of resolution [logMAR] [95% confidence interval {CI} 0.27-0.43]; n = 32) and UT-DSAEK (0.37 logMAR [95% CI 0.31-0.43]; n = 34; P = 0.8). BSCVA was significantly better after UT-DSAEK compared with that after DSAEK at 3 months (0.17 logMAR [95% CI 0.13-0.21], n = 31 vs. 0.28 logMAR [95% CI 0.23-0.33], n = 31; P = 0.001), 6 months (0.14 logMAR [95% CI 0.10-0.18], n = 30 vs. 0.24 logMAR [95% CI 0.20-0.28], n = 30; P = 0.002), and 12 months (0.13 logMAR [95% CI 0.09-0.17], n = 33 vs. 0.20 logMAR [95% CI 0.15-0.25], n = 29; P = 0.03). Refraction, ECD loss (40% at 3 months; P < 0.001), donor loss (DSAEK n = 2 vs. UT-DSAEK n = 3 [relative risk {RR} 1.4 {95% CI 0.24-7.5}; P = 0.7]), and graft dislocation (DSAEK n = 5 vs. UT-DSAEK n = 5 [RR 1.0 {95% CI 0.34-3.33}; P = 0.9]) did not differ between UT-DSAEK and DSAEK. Donor thickness was significantly thinner for UT-DSAEK (101 µm [95% CI 93-110 µm]; range 50-145 µm) than for DSAEK (209 µm [95% CI 196-222 µm]; range 147-289 µm; P < 0.001). CONCLUSIONS: This study indicates that compared with DSAEK, UT-DSAEK results in faster and better recovery of BSCVA with similar refractive outcomes, endothelial cell loss, and incidence of complications.

Cataract surgery in patients with Fuchs' endothelial corneal dystrophy: when to consider a triple procedure.

PURPOSE: To ascertain preoperative and intraoperative factors that predict the need for endothelial keratoplasty (EK) in patients with Fuchs' endothelial corneal dystrophy (FECD) undergoing cataract surgery. DESIGN: Prospective, observational cohort study. PARTICIPANTS: Eighty-nine patients (89 eyes) with FECD who require cataract surgery. METHODS: One month before cataract surgery, we assessed best-corrected visual acuity, contrast sensitivity, straylight, keratometry, ultrasonic pachymetry, intraocular pressure, 7 corneal features of FECD and cataract density at slit-lamp examination, and corneal backscatter using in vivo confocal microscopy (IVCM; Confoscan 4, NIDEK Technologies, Padova, Italy). After surgery, measurements were repeated at 1, 2, and 12 months. We used stepwise binary logistic regression analysis to evaluate 30 preoperative and 5 intraoperative parameters for their ability to predict the postoperative need for EK. Receiver operating characteristic (ROC) curves of the predictive factors were used to identify their optimal cutoff points. MAIN OUTCOME MEASURES: Central corneal thickness (CCT) and backscatter at the basal epithelial cell layer (EV). RESULTS: After cataract surgery, 35 (39%) of 89 eyes underwent EK to restore vision. Of all preoperative and intraoperative parameters, only CCT and EV were identified as significant factors, predictive of the need for EK. The area under the ROC curve of EV was significantly higher than that of CCT (P = 0.003), whereas a combination of both factors in a linear discriminant function did not improve the predictive value (P = 0.66). As optimal cutoff points, we chose 1894 scatter units for EV and 630 µm for CCT. Both cutoff points correspond with a specificity of 94% and represent sensitivity of 63% for EV and 40% for CCT. CONCLUSIONS: Backscatter at the basal epithelial cell layer measured by IVCM predicts the need for EK after cataract surgery in patients with FECD. As an indicator for the corneal hydration state, the EV improves patient selection for combined cataract surgery and EK. In deciding whether to perform a triple procedure, CCT remains a less effective, but adequate, alternative. Regardless of the predictive factor used, a tailor-made approach is recommended accounting for individuals' expectations.

Ocular infections in sub-Saharan Africa in the context of high HIV prevalence.

Healthy eyes and good vision are important determinants of populations' health across the globe. Sub-Saharan Africa is affected by simultaneous epidemics of ocular infections and human immunodeficiency virus (HIV). Ocular infection and its complications, along with cataract and ocular trauma, are common conditions in this region with great impact on daily life. In this review, we discuss the epidemiology, clinical manifestations and microbial aetiology of the most important infectious ocular conditions in sub-Saharan Africa: conjunctivitis, keratitis and uveitis. We focus specifically on the potential association of these infections with HIV infection, including immune recovery uveitis. Finally, challenges and opportunities for clinical management are discussed, and recommendations made to improve care in this neglected but very important clinical field.

Self-limiting corneal edema with multiple parallel lines on the endothelium (SCEMPLE).

The purpose of this study was to report the natural course and in vivo confocal microscopy (IVCM) findings of five cases with unilateral self-limiting corneal edema and multiple parallel lines on the endothelium (SCEMPLE). This study is an observational case series. Five patients, who experienced a blurred vision due to SCEMPLE, were studied using slit-lamp examination and white-light IVCM (Confoscan 4; Nidek Technologies, Padova, Italy). IVCM of the linear deposits revealed characteristic hyperreflective material protruding between the endothelial cells. The lines also displayed spot-like holes and polygonal precipitates, which resembled dislodged endothelial cells. Because other signs of corneal inflammation, such as stromal infiltration and ciliary injection, were lacking, the condition was left untreated. After 1 day, slit-lamp examination and IVCM revealed only a small residual of the lines. Spontaneous, complete resolution occurred in all five cases within 1 week, leaving a lower endothelial cell density of the affected eyes as only sequela. SCEMPLE requires no treatment but may result in endothelial cell loss. The self-limiting character and IVCM appearance dispute SCEMPLE being a form of endotheliitis and suggest a different etiology.

Acyclovir prophylaxis predisposes to antiviral-resistant recurrent herpetic keratitis.

PURPOSE: Long-term acyclovir (ACV) prophylaxis, recommended to prevent recurrent herpes simplex virus type 1 (HSV-1) ocular disorders, may pose a risk for ACV-refractory disease due to ACV resistance. We determined the effect of ACV prophylaxis on the prevalence of corneal ACV-resistant (ACV(R)) HSV-1 and clinical consequences thereof in patients with recurrent HSV-1 keratitis (rHK). METHODS: Frequencies of ACV(R) viruses were determined in 169 corneal HSV-1 isolates from 78 rHK patients with a history of stromal disease. The isolates' ACV susceptibility profiles were correlated with clinical parameters to identify risk factors predisposing to ACV(R) rHK. RESULTS: Corneal HSV-1 isolates with >28% ACV(R) viruses were defined as ACV(R) isolates. Forty-four isolates (26%) were ACV-resistant. Multivariate analyses identified long-term ACV prophylaxis (≥12 months) (odds ratio [OR] 3.42; 95% confidence interval [CI], 1.32-8.87) and recurrence duration of ≥45 days (OR 2.23; 95% CI, 1.02-4.87), indicative of ACV-refractory disease, as independent risk factors for ACV(R) isolates. Moreover, a corneal ACV(R) isolate was a risk factor for ACV-refractory disease (OR 2.28; 95% CI, 1.06-4.89). CONCLUSIONS: The data suggest that long-term ACV prophylaxis predisposes to ACV-refractory disease due to the emergence of corneal ACV(R) HSV-1. ACV-susceptibility testing is warranted during follow-up of rHK patients.

Latent acyclovir-resistant herpes simplex virus type 1 in trigeminal ganglia of immunocompetent individuals.

Specific mutations within the hypervariable herpes simplex virus (HSV) gene thymidine kinase (TK) gene lead to acyclovir (ACV) resistance. To uncover the existence of latent ACV-resistant (ACV(R)) HSV-1, we determined the genetic and functional variability of the HSV-1 TK gene pool in paired trigeminal ganglia (TG) of 5 immunocompetent individuals. The latent virus pool consisted of a donor-specific HSV-1 quasispecies, including one major ACV-sensitive (ACV(S)) and multiple phylogenetic-related minor ACV(S) and ACV(R) TK variants. Contrary to minor variants, major TK variants were shared between paired TG. The data demonstrate the coexistence of phylogenetic-related ACV(S) and ACV(R) latent HSV-1 in human TG.

Allogeneic Serum Eye Drops: A Randomized Clinical Trial to Evaluate the Clinical Effectiveness of Two Drop Sizes.

INTRODUCTION: Allogeneic serum from blood donors is starting to be used to treat patients with dry eye disease (DED). However, the optimal dose is not known. We therefore aimed to evaluate the clinical efficaciousness and user-friendliness of micro-sized versus conventional-sized allogeneic serum eye drops (SEDs). METHODS: In a randomized trial, patients with DED first receive micro-sized SEDs (7 µl/unit) for 1 month, followed by a 1-month washout, before receiving conventional-sized SEDs (50 µl/unit) for 1 month; or vice versa. The primary endpoint was the Ocular Surface Disease Index (OSDI) score. Secondary endpoints were tear break-up time (TBT), tear production (TP), and presence of corneal punctate lesions (CP). The user-friendliness of both application systems was also compared. A linear mixed model for cross-over design was applied to compare both treatments. RESULTS: Forty-nine patients completed the trial. The mean OSDI score significantly improved from 52 ± 3 to 41 ± 3 for micro-sized SEDs, and from 54 ± 3 to 45 ± 3 for conventional-sized SEDs. Non-inferiority (margin = 6) of micro-sized SEDs was established. We demonstrate a significant improvement for TBT in case of conventional-sized SEDs and for CP in both treatment groups. TP trended towards an improvement in both treatment groups. The user-friendliness of the conventional drop system was significantly higher. CONCLUSIONS: For the first time, non-inferiority of micro-sized allogeneic SEDs was established. The beneficial effect of both SED volumes was similar as measured by the OSDI score. Although user-friendliness of the micro drop system was significantly lower, it is an attractive alternative as it saves valuable donor serum. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03539159).

How normal is the transparent cornea? Effects of aging on corneal morphology.

PURPOSE: To ascertain the effects of aging on corneal morphology and to illustrate the morphologic diversity of the different layers in the normal cornea as seen by in vivo confocal microscopy (IVCM). DESIGN: Observational cross-sectional study. PARTICIPANTS: A total of 150 healthy subjects, evenly distributed over 5 age categories, comprising 75 men and 75 women. METHODS: Both transparent corneas (n = 300) of all subjects were examined in duplicate by white light IVCM (Confoscan 4, NIDEK Technologies, Albignasego, Padova, Italy). After reviewing the IVCM examinations for morphologic variations of the corneal layers, we selected the 8 most common features to illustrate the morphologic diversity. Subsequently, all 600 IVCM examinations were assessed for the presence of these features. We used binary logistic regression analyses to assess the age-relatedness of each feature. MAIN OUTCOME MEASURES: Age distribution of bright superficial epithelial cells, dendriform cells, alterations characteristic of epithelial basement membrane dystrophy (EBMD), tortuous stromal nerves, stromal microdots in the anterior stroma, folds in the posterior stroma, opacification of Descemet's membrane, and corneal guttae. RESULTS: Four features were found characteristic of the aging cornea: stromal microdots in the anterior stroma (P<0.0001), folds in the posterior stroma (P<0.0001), opacification of Descemet's membrane (P<0.0001), and corneal guttae (P<0.0001). Alterations characteristic of EBMD were found in 3% of all eyes and only detected in subjects aged ≥40 years, suggesting age-relatedness (P = 0.09). Other features, such as bright superficial epithelial cells (n = 38, 13%), dendriform cells (n = 42, 14%), and tortuous stromal nerves (n = 115, 38%), were age-independent. We also found a novel phenotype of corneal endothelium in 4 normal eyes of 2 subjects, which we coined "salt and pepper endothelium." We could not establish whether this novel phenotype represented a morphologic variant of normal endothelium, an early stage of a known corneal endothelial disorder, or a completely new disease entity. CONCLUSIONS: Knowledge of the common morphologic variations of the corneal layers and the effects of aging on corneal morphology as seen by IVCM increases our understanding of corneal degenerative disorders and is essential to detect corneal pathology. Our finding of a novel phenotype of corneal endothelium emphasizes the morphologic diversity of this optically transparent tissue.

Monitoring the inflammatory process in herpetic stromal keratitis: the role of in vivo confocal microscopy.

PURPOSE: To investigate the role of in vivo confocal microscopy (IVCM) in the detection of inflammatory activity and follow-up of herpetic stromal keratitis (HSK). DESIGN: Prospective observational cohort study. PARTICIPANTS: Thirty-eight patients with active HSK. METHODS: Within 7 days after diagnosis of active HSK, both eyes of each patient were examined by slit-lamp biomicroscopy and white-light IVCM (Confoscan 4; Nidek Technologies, Padova, Italy). The HSK-affected eyes were followed up at 1, 3, 6, and 12 months, whereas the unaffected fellow eyes were reexamined after 12 months. Three patients did not complete follow-up and were excluded for data analyses. All IVCM examinations were assessed for morphologic alterations characteristic of inflammatory activity and for corneal backscatter. As secondary outcome parameters, best-corrected visual activity (BCVA), central corneal thickness (CCT), intraocular pressure (IOP), and endothelial cell density (ECD) were determined at each study visit. We used repeated-measures analysis of variance to assess changes during the 12-month follow-up period and paired t tests to compare HSK-affected eyes with fellow eyes. MAIN OUTCOME MEASURES: Presence of dendriform cells, pseudoguttae, and keratic precipitates, and follow-up of mean corneal backscatter. RESULTS: An increase of dendriform cells and pseudoguttae often accompanied stromal infiltration. Because these IVCM parameters were indiscernible or overlooked at slit-lamp examination, they proved to be excellent indicators of inflammatory activity. At 12 months' follow-up, mean corneal backscatter had decreased significantly by 36%, but still fell outside the normal range in 24 (69%) of the HSK-affected eyes. By using slit-lamp in conjunction with IVCM, we detected 17 recurrences in 14 of 35 patients (40%). Three of these recurrences were missed by slit-lamp, and 6 of these were missed by IVCM. At 12 months' follow-up, BCVA (-9 letters), CCT (-36 µm), and ECD (-313 cells/mm(2)) were significantly lower, whereas IOP (1.8 mmHg) was significantly higher, in HSK-affected eyes compared with fellow eyes. CONCLUSIONS: The data presented demonstrate that IVCM is complementary to slit-lamp examination in the follow-up of HSK, particularly because of its power to detect early signs of intracorneal inflammatory activity. Therapy guidance based on morphologic assessment and corneal backscatter measurement by combined IVCM and slit-lamp examination may improve the outcome of HSK. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Cluster of Symptomatic Graft-to-Host Transmission of Herpes Simplex Virus Type 1 in an Endothelial Keratoplasty Setting.

Purpose: Descemet's membrane endothelial keratoplasty (DMEK) is becoming the gold standard to treat corneal endothelial dysfunctions worldwide. Compared with conventional penetrating keratoplasty, infectious complications after DMEK are ill defined. We describe the clinical picture of 2 DMEK recipients, operated on the same day and in the same clinic, who developed atypical herpes simplex virus type 1 (HSV-1) infection in the transplant recipient eye within days post-DMEK. Because recipients received cornea tissue from 2 different donors prepared by the same eye bank, the likelihood of a common HSV-1 source was determined. Design: Case series. Participants: Two DMEK recipients who developed atypical intraocular HSV-1 disease shortly after surgery and surplus cornea specimens of 6 donors. Methods: Surplus cornea donor (pre-DMEK cornea remnants and conditioned cornea storage and transport media) and recipient samples (post-DMEK aqueous humor) were assayed for HSV-1 DNA and infectious virus by real-time polymerase chain reaction (RT-PCR) and cell culture, respectively. Target-enriched whole viral genome sequencing was performed on HSV-1 DNA-positive ocular specimens. Main Outcome Measures: Clinical picture of atypical intraocular HSV-1 infection post-DMEK and presence and homology of HSV-1 genomes between ocular specimens of DMEK donors and recipients. Results: Herpes simplex virus type 1 DNA was detected in aqueous humor and donor cornea specimens of both DMEK cases, but not in the cornea remnants of 6 randomly selected donors processed by the same eye bank. Infectious HSV-1 was isolated from the cornea remnant and corresponding culture medium of 1 cornea donor. Notably, whole-genome sequencing of virus DNA-positive specimens demonstrated exceptionally high genetic similarity between HSV-1 strains in recipient and donor specimens of both DMEK cases. Conclusions: Data indicate cross-contamination of cornea grafts during DMEK preparation with subsequent graft-to-host HSV-1 transmission that caused atypical sight-threatening herpetic eye disease shortly after DMEK. Ophthalmologists should be aware that HSV-1 transmission by DMEK is possible and can lead to atypical ocular disease, a condition that can easily be prevented by taking appropriate technical and clinical measures at both eye bank and surgical levels.

Zipper cell endotheliopathy: a new subset of idiopathic corneal edema.

PURPOSE: To report the clinical and histologic findings of a new subset of idiopathic corneal edema: zipper cell endotheliopathy. DESIGN: Observational case report. PARTICIPANT: A 55-year-old woman with unilateral bullous keratopathy. METHODS: Clinical observation consisted of slit-lamp examination and in vivo confocal microscopy (IVCM). Aqueous humor samples and the excised corneal button were analyzed for the presence of herpes viruses. The excised cornea was subjected to detailed immunohistochemistry (IHC) and scanning and transmission electron microscopy. MAIN OUTCOME MEASURES: Clinical and pathologic characteristics of zipper cell endotheliopathy. RESULTS: In vivo confocal microscopy revealed unique morphologic alterations of the corneal endothelial layer. Focal areas of denudation were surrounded by endothelial cells with zipper-like cell borders and intercellular structures. Besides central corneal edema, no other signs of corneal inflammation were detected. A herpes virus origin for the bullous keratopathy was excluded. The IHC analysis disclosed positive staining for cytokeratin (CK) 7, CK8/18, and CK19, suggesting epithelial metaplasia of the endothelial cells. Ultrastructural examination confirmed the IVCM findings by showing large areas of endothelial denudation and vacuolated endothelial cells with large, broad-based extensions that partially overlapped neighboring cells. Despite extensive complementary research and review of the literature, the endothelial alterations could not be attributed to any known corneal disorder. CONCLUSIONS: To the authors' knowledge, zipper cell endotheliopathy is a new subset of idiopathic corneal edema. The case report presented illustrates the potential use of IVCM to differentiate the spectrum of corneal disorders and to discover new corneal diseases.

Acyclovir susceptibility and genetic characteristics of sequential herpes simplex virus type 1 corneal isolates from patients with recurrent herpetic keratitis.

PURPOSE: The incidence and clinical significance of herpes simplex virus type 1 (HSV-1) acyclovir resistance were determined in patients with recurrent herpetic keratitis (RHK). METHODS: Sequential corneal isolates (n = 39) from 15 immunocompetent patients with RHK were assayed for acyclovir susceptibility and genotyped by analyzing the hypervariable regions of the HSV-1 genes US1 and US12. The thymidine kinase (TK) gene of each isolate was sequenced, and the proportion of acyclovir-resistant viruses within isolates was determined. RESULTS: Uniform acyclovir-resistant or acyclovir-sensitive sequential isolates were identified in 4 and 2 patients, respectively. Notably, the acyclovir susceptibility of sequential isolates changed from acyclovir sensitive to acyclovir resistant (5 patients) or from acyclovir resistant to acyclovir sensitive (3 patients). The acyclovir-resistant phenotype of the isolates correlated with the patient's unresponsiveness to acyclovir therapy. Combined analyses of the TK gene and genotype of sequential isolates showed that acyclovir-sensitive isolates contained multiple acyclovir-resistant variants of the same virus and that an identical acyclovir-resistant HSV-1 strain reappeared in the patient's cornea during RHK episodes. CONCLUSIONS: Corneal HSV-1 isolates are mixtures of acyclovir-sensitive and acyclovir-resistant viruses that share the same genotype but have different TK sequences. Recovery of the same acyclovir-resistant virus during consecutive herpetic keratitis episodes suggests that acyclovir-resistant HSV-1 establishes latency and reactivates intermittently to cause acyclovir-refractory RHK.

The learning curve for Descemet membrane endothelial keratoplasty performed by two experienced corneal surgeons: a consecutive series of 40 cases.

PURPOSE: To describe the learning curve for Descemet's membrane endothelial keratoplasty (DMEK) in the Rotterdam Eye Hospital and to evaluate safety and visual outcome. METHODS: This was a single-centre prospective study of 40 consecutive patients with Fuchs' endothelial dystrophy who underwent a DMEK procedure in the Rotterdam Eye Hospital. The performance of two corneal surgeons, each conducting their first series of 20 procedures, was examined with the cumulative summation test for the learning curve (LC-CUSUM). The surgical procedure was considered unsuccessful when >30% of the graft was not attached at any time during the first 12 postoperative weeks and a mixture of SF6 (20%) and air (80%) had to be injected in the anterior chamber (rebubbling) to reattach the graft. Also assessed were visual outcome, intraocular pressure and peri- and postoperative complications. RESULTS: In total, nine rebubbling procedures were performed in seven eyes. Following repeated rebubbling, two eyes did not achieve a satisfactory result and secondary surgery was required to restore visual function. Complications were usually manageable. The last 13 DMEK procedures (33%) of this series did not require rebubbling. After 3 months, 86% of the eyes had reached a Snellen visual acuity of 0.5 or more. CONCLUSION: Together with the two surgeons' personal experience, the aggregate learning curve was considered to justify incorporation of Descemet membrane endothelial keratoplasty as a regular option of the standard of care for endothelial dysfunction in the Rotterdam Eye Hospital.

Endothelial involvement in herpes simplex virus keratitis: an in vivo confocal microscopy study.

PURPOSE: To describe the appearance, frequency, and clinical consequences of corneal endothelial involvement in human herpes simplex virus (HSV) keratitis as seen by in vivo confocal microscopy (IVCM). DESIGN: Prospective observational case series. PARTICIPANTS: A total of 285 patients with HSV keratitis who visited the cornea department of the Rotterdam Eye Hospital between May 2005 and May 2008. The control groups comprised the unaffected fellow eyes of patients with HSV keratitis, the eyes of 58 healthy volunteers, and the affected eyes of 62 patients with inflammatory corneal disorders other than HSV. METHODS: We examined the eyes of all participants by IVCM and slit-lamp examination. For IVCM, corneas were scanned with Confoscan 3 or 4 (Nidek Technologies, Albignasego, Padova, Italy). MAIN OUTCOME MEASURES: All IVCM examinations were qualitatively reviewed for signs of endothelial deviations characteristic of endotheliitis. Endothelial cell density (ECD) was evaluated on the first and last visits of patients who were followed for more than 100 days. The differences in ECDs were calculated and converted to percent ECD change per year. RESULTS: Endothelial alterations characteristic of endotheliitis were detected by IVCM in 107 of 250 patients with HSV keratitis (43%). These deviations consisted of pseudoguttata, enlarged intercellular gaps, infiltration of inflammatory cells into the endothelial layer, loss of defined cell boundaries, spot-like holes, and endothelial denudation. All of these signs disappeared with appropriate antiviral and anti-inflammatory treatment. However, the endothelium in eyes with endotheliitis-characteristic alterations showed a significant decrease in ECD (10.3% per year) compared with healthy fellow eyes. CONCLUSIONS: IVCM allows earlier detection of endothelial alterations in patients with HSV keratitis compared with slit-lamp examination. Although endotheliitis-specific alterations appear to resolve, the corneal endothelium can become irreversibly damaged.

Trial-based cost-effectiveness analysis of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) versus DSAEK.

PURPOSE: To evaluate the cost-effectiveness of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) versus standard DSAEK. METHODS: A cost-effectiveness analysis using data from a multicentre randomized clinical trial was performed. The time horizon was 12 months postoperatively. Sixty-four eyes of 64 patients with Fuchs' endothelial dystrophy were included and randomized to UT-DSAEK (n = 33) or DSAEK (n = 31). Relevant resources from healthcare and societal perspectives were included in the cost analysis. Quality-adjusted life years (QALYs) were determined using the Health Utilities Index Mark 3 questionnaire. The main outcome was the incremental cost-effectiveness ratio (ICER; incremental societal costs per QALY). RESULTS: Societal costs were €9431 (US$11 586) for UT-DSAEK and €9110 (US$11 192) for DSAEK. Quality-adjusted life years (QALYs) were 0.74 in both groups. The ICER indicated inferiority of UT-DSAEK. The cost-effectiveness probability ranged from 37% to 42%, assuming the maximum acceptable ICER ranged from €2500-€80 000 (US$3071-US$98 280) per QALY. Additional analyses were performed omitting one UT-DSAEK patient who required a regraft [ICER €9057 (US$11 127) per QALY, cost-effectiveness probability: 44-62%] and correcting QALYs for an imbalance in baseline utilities [ICER €23 827 (US$29 271) per QALY, cost-effectiveness probability: 36-59%]. Furthermore, the ICER was €2101 (US$2581) per patient with clinical improvement in best spectacle-corrected visual acuity (≥0.2 logMAR) and €3274 (US$4022) per patient with clinical improvement in National Eye Institute Visual Functioning Questionnaire-25 composite score (≥10 points). CONCLUSION: The base case analysis favoured DSAEK, since costs of UT-DSAEK were higher while QALYs were comparable. However, additional analyses revealed no preference for UT-DSAEK or DSAEK. Further cost-effectiveness studies are required to reduce uncertainty.

Graft insertion during Descemet-stripping automated endothelial keratoplasty: pulling the graft inward.

We describe a technique to facilitate insertion of the folded donor graft during Descemet-stripping automated endothelial keratoplasty (DSAEK). Surgery is performed using a standard technique, and the graft is pulled into the anterior chamber using a double-armed 10-0 polypropylene suture with straight 16 mm needles. The technique of pulling the graft inside the anterior chamber is easy and ensures that the graft is inserted and unfolded in the right direction. There is no compression of tissue so mechanical trauma to the endothelium is less than when an inserting forceps is used. The results in 12 cases are presented.

Corneal transplantation for Fuchs´ endothelial dystrophy: A comparison of three surgical techniques concerning 10 year graft survival and visual function.

OBJECTIVE: Comparison of conventional Penetrating Keratoplasty (PKP), posterior mushroom PKP and Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) regarding overall graft survival of primary corneal transplants for Fuchs´ endothelial dystrophy (FED), best spectacle-corrected visual acuity (BSCVA) and astigmatism. METHODS: Single centre study using prospectively collected data from the national database for follow-up of corneal transplants. Main outcome parameters: 10 years graft survival, astigmatism at 24 months, pre- and post-operative BSCVA. RESULTS: In total, 721 cases were included: PKP, n = 171; posterior mushroom PKP, n = 91; and DSAEK, n = 459. There was no significant difference in graft survival between PKP, posterior mushroom PKP and the DSAEK technique (log-rank test, P = 0.12). The overall post-operative BSCVA improvement in all treatment groups was significant (paired t-test, P<0.001). Pre-operative BSCVA was better for the DSAEK group (0.68 ± 0.41 logMAR) as compared to the PKP (0.89 ± 0.53) and posterior mushroom PKP group (0.90 ± 0.58); ANOVA, P<0.001. After 24 months, BSCVA was significantly better for the DSAEK group (0.25 ± 0.26 logMAR) compared to the PKP (0.35 ± 0.29) and posterior mushroom PKP group (0.41 ± 0.42); ANOVA, P<0.001. A significant difference in astigmatism was found (median test, P<0.001) between the DSAEK (1.7 ± 1.1 D), PKP (4.6 ± 2.7 D) and posterior mushroom PKP group (4.5 ± 3.3 D). The significantly lower DSAEK-induced astigmatism was confirmed by vector analysis. CONCLUSION: There was no difference in graft survival and BSCVA improvement between conventional PKP, inverted mushroom PKP and DSAEK in this study. The significantly lower changes in astigmatism, wound stability and faster visual rehabilitation with DSAEK surgery are favourable aspects of this technique. The benefits of posterior lamellar keratoplasty warrant earlier intervention, which may contribute to preserve better vision for a prolonged period of remaining lifetime.

Long-Term Functional and Anatomical Outcome after Descemet Stripping Automated Endothelial Keratoplasty: A Prospective Single-Center Study.

PURPOSE: To investigate the long-term anatomical and functional outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Prospective follow-up of 114 eyes (95 subjects) after DSAEK for endothelial dysfunction. Measurements included best spectacle-corrected visual acuity (BSCVA), straylight, endothelial cell density (ECD), and graft thickness. RESULTS: The mean follow-up time was 5.1 ± 1.5 years. Four grafts ultimately failed (after 5 to 7 years). From baseline up to 1 year after DSAEK, mean BSCVA improved by 0.30 logMAR. This beneficial effect remained until the last follow-up (LFU). After DSAEK, straylight was reduced. ECD sharply dropped by 900 cells/mm2 (33%) immediately after surgery and, thereafter, steadily decreased at a rate of 11 cells/mm2 per month. No significant correlation was observed between graft thickness at 3 years and BSCVA. CONCLUSIONS: We observed a low graft failure rate and a normalization of graft thickness. Postoperative straylight remained elevated relative to the normal population. The sharp initial and the subsequent more gradual ECD decline are consistent with other studies. A significant and prolonged functional gain can be achieved by posterior lamellar grafting for endothelial dysfunction.

Granulocyte macrophage colony-stimulating factor expression in human herpetic stromal keratitis: implications for the role of neutrophils in HSK.

PURPOSE: Granulocyte macrophage colony-stimulating factor (GM-CSF) is thought to play a key role in chronic inflammatory diseases by governing the survival and function of infiltrating neutrophils. The objective of this study was to determine the putative role of GM-CSF in the pathogenesis of human herpetic stromal keratitis (HSK). METHODS: Primary human corneal fibroblast (HCF) cultures and a telomerase-immortalized human corneal epithelial (HCE) cell line representative of native HCE were stimulated with the known HSK-inducing cytokines interferon (IFN)-gamma, interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha. Alternatively, the T-cell cytokine IL-17 was added solely or simultaneously. Human neutrophils were incubated with conditioned medium (CM) of the HCF and HCE stimulated with the aforementioned cytokines, or recombinant GM-CSF, and their viability or activation status was determined by flow cytometry. GM-CSF and IL-8 secretion levels in the CM were determined by ELISA. The antibody-dependent cellular cytotoxicity (ADCC) of neutrophils toward herpes simplex virus (HSV)-infected HCFs was determined by flow cytometry. The expression of GM-CSF was determined in HSK and control corneal buttons by real-time RT-PCR and immunohistology. RESULTS: Compared with IFN-gamma, CM of either cell type stimulated with IL-1beta, or in the case of HCE cells, stimulated with TNF-alpha or IL-17, delayed neutrophil apoptosis significantly. Only in HCFs did IL-17 exhibit a synergistic effect with TNF-alpha. The antiapoptotic activity was attributable in part to the GM-CSF secreted by the activated HCFs and HCE cells. GM-CSF stimulation of neutrophils induced their activation and the secretion of IL-8. GM-CSF did not increase significantly the ADCC reaction of neutrophils toward HSV-infected HCFs. Finally, GM-CSF was expressed in corneas of the patients with HSK but not in control subjects. CONCLUSIONS: The data suggest that GM-CSF, expressed by cornea-resident cells such as HCFs and HCE cells, may play a role in the immunopathogenesis of HSK by prolonging the survival and modulating the effector function of corneal infiltrating neutrophils.