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.

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.

Higher-order aberrations 1 year after corneal collagen crosslinking for keratoconus and their independent effect on visual acuity.

PURPOSE: To evaluate the effect of corneal collagen crosslinking (CXL) in progressive keratoconus patients on higher-order aberrations (HOAs) and the effect of change in HOAs on visual acuity between baseline and 1 year after CXL. SETTING: Tertiary academic referral center, Utrecht, the Netherlands. DESIGN: Prospective cohort study. METHODS: This study included consecutive keratoconus patients who were treated with epithelium-off CXL and followed for a minimum of 1 year. The following corneal HOAs were measured with Scheimpflug tomography (Pentacam HR type 70900): coma, trefoil, spherical aberration, and total corneal HOAs. A 2-tailed paired-samples t test was used to compare baseline and postoperative aberrations. Multivariable linear regression was applied to assess the independent effects of HOA subtypes on changes in uncorrected (UDVA) and corrected (CDVA) distance visual acuity. RESULTS: Overall, the degree of corneal HOAs in the patient cohort (N = 187) was relatively unchanged after CXL, with a mean change of -1.34% (P = .272). Horizontal coma contributed most to the total amount of HOAs but was virtually unchanged on average. The HOA subtype of spherical aberrations decreased significantly (-15.68%) (P < .001). There was no effect of the change in HOAs on the change in CDVA; however, there was a significant effect of the change in horizontal coma on the change in UDVA (P = .003; B -0.475). CONCLUSIONS: Corneal HOAs in general were relatively unchanged from baseline to 1 year after CXL in eyes with progressive keratoconus. A change in horizontal coma had a strong and independent effect on UDVA. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Comparison of Diaton transpalpebral tonometer with applanation tonometry in keratoconus.

AIM: To investigate the added value of using a Diaton transpalpebral tonometer (DT) to measure IOP in keratoconus. Most type of tonometers use corneal applanation or biomechanical resistance to measure intraocular pressure (IOP); however, these factors can be altered by keratoconus. Specifically, we examined whether DT can detect false-negative low Goldmann applanation tonometry (AT) measurements. METHODS: Patients with keratoconus were recruited from our tertiary academic treatment center. Measurements included AT and DT (in random order) and Scheimpflug imaging. An age- and gender-matched group of control subjects with no history of corneal disease or glaucoma was also recruited. RESULTS: In total, 130 eyes from 66 participants were assessed. In the keratoconus group, mean AT was 11.0 ± 2.6, mean DT 11.2±5.5 (P=0.729), and the two measures were correlated significantly (P=0.006, R=0.323). However, a Bland-Altman plot revealed a wide distribution and poor agreement between both measurements. Previous corneal crosslinking, corneal pachymetry, and Krumeich classification had no effect on measured IOP. CONCLUSION: Measurements obtained using a Diaton tonometer are not affected by corneal biomechanics; however, its poor agreement with Goldmann AT values calls into question the added value of using a Diaton tonometer to measure IOP in keratoconus.

Objective and subjective evaluation of the performance of medical contact lenses fitted using a contact lens selection algorithm.

PURPOSE: To evaluate the performance of medical contact lenses (CLs) for a wide range of clinical indications. DESIGN: Prospective cross-sectional study. METHODS: A total of 281 eyes were evaluated in 281 consecutive patients (≥18 years of age; CL use ≥3 months) who visited the contact lens service in a tertiary academic clinic for a scheduled follow-up visit. The main outcome measured were clinical indications for CL wear; CL type; change in corrected distance visual acuity (CDVA) with CL use; CL wearing duration; CL wearing time; subjective performance measured using a visual analog scale (VAS) questionnaire (score range: 0-100); and effectiveness of the lens-selection algorithm. RESULTS: Wearing CLs significantly improved CDVA compared to wearing spectacles (median change: -0.15 logMAR, range: 1.00 to -2.10; P<.001). Daily-wear CLs were worn by 77% of patients for a median of 15h/day (range: 5-18h/day), median 7 days/week (range: 1-7 days/week). High subjective scores were measured, with similar results obtained between the scleral lens and soft lens groups. The medical CL fitting was found to be generally effective (the overall satisfaction rating was ≥70 for 81% of patients). CONCLUSIONS: Fitting CLs based on the lens-selection algorithm yielded positive clinical results, including improved visual acuity, satisfactory wearing time, and high overall subjective performance. Moreover, subjective performance was similar between users of scleral lenses and users of soft lenses. These results underscore the importance of prescribing scleral lenses and the need for tertiary eye clinics to offer patients a variety of CL types.

Cytokine Expression in Keratoconus and its Corneal Microenvironment: A Systematic Review.

Keratoconus (KC) is a progressive corneal ecstasia characterized by thinning and weakening of the cornea that leads to a cone-like appearance, scarring, and decreased vision. Despite the well-described clinical signs, the cause of KC is unknown. Nevertheless, various genes, proteinases, and environmental factors (eye-rubbing, contact lens wear, tear film composition) have been implicated in its etiology. Although classically defined as a predominantly degenerative disease, with mechanically induced trauma accelerating its course, accumulating evidence suggests a pivotal role for inflammation in the pathophysiology of KC. Several reports have linked various inflammatory mediators (cytokines) with KC, but with contradictory findings. The methods and materials used in these studies vary considerably and warrant critical evaluation to decipher the role of inflammatory mediators in KC. We performed a systematic review of current literature on cytokine expression studies in KC and discuss critical soluble and cellular inflammatory mediators that are implicated in its pathogenesis.

Effect of the eyelid speculum on pachymetry during corneal collagen crosslinking in keratoconus patients.

PURPOSE: To compare central corneal thickness (CCT) with and without using an eyelid speculum during corneal collagen crosslinking (CXL). SETTING: University Medical Center Utrecht, Utrecht, the Netherlands. DESIGN: Prospective nonrandomized comparative study. METHODS: Eyes with progressive keratoconus were treated by CXL and consecutively divided into 2 groups. In Group A, an eyelid speculum remained in place throughout the entire CXL procedure. In Group B, the eyelids remained closed during the 30-minute riboflavin instillation. Intraoperative ultrasound pachymetry measurements were performed at different timepoints. The visual acuity, refraction, keratometry, pachymetry, and endothelium were evaluated 6 months after CXL. The main outcome measures were intraoperative CCT measurements and the clinical CXL effect after 6 months. RESULTS: Fifty-two eyes (50 patients) were treated. After riboflavin instillation, a statistically significant difference in CCT reduction was found between the 2 groups (P<.001), with a mean CCT decrease of 62 µm±53 (SD) (13%±11%) in Group A and 11±35 µm (2%±8%) in Group B. No statistically significant between-group differences were found after epithelial removal or ultraviolet-A (UVA) irradiation. Six months after CXL, no statistically significant between-group difference was found in the visual acuity, refraction, keratometry, pachymetry, or endothelium. CONCLUSIONS: Avoidance of an eyelid speculum during riboflavin instillation resulted in less CCT reduction during CXL. This finding could increase the chance of attaining the required pachymetry safety margin for applying UVA and thus decrease the chance of premature CXL treatment termination. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

DSAEK: practical approach to choose the microkeratome head on the basis of donor cornea pachymetry.

PURPOSE: The aim of this study was to supply data on the relationship between Descemet stripping automated endothelial keratoplasty (DSAEK) graft thickness and its effects on visual acuity (VA), pace of visual recovery, endothelial cell densities (ECDs), and surgical complications. We additionally provide an approach for choosing the microkeratome blade thickness when multiple patients are scheduled for DSAEK. METHODS: This is a retrospective analysis of all DSAEK procedures performed at our institute from January 2011 to December 2012. The VA was assessed at all postop visits. The ECD was assessed at 6 and 12 months postoperatively. An algorithm based on donor cornea pachymetry was used to assist in the choice of a microkeratome blade either 350 or 400 µm thick. Two groups were created on the basis of the microkeratome blade chosen. Outcomes were given per treatment group. RESULTS: One hundred two consecutive DSAEK procedures were performed; 60 grafts were prepared with the 350-µm blade and 39 with the 400-µm blade. Baseline characteristics did not differ materially. Grafts dissected using the 350-µm knife were significantly thicker than the grafts dissected with the 400-µm blade, with values of 257 ± 47 µm and 222 ± 33 µm, respectively (P = 0.01). The pace of visual recovery, VA at maximum follow-up, and ECD did not differ significantly between groups. Surgical complications were evenly distributed over both groups. CONCLUSIONS: This study indicates that using neither the 350-µm nor 400-µm microkeratome blade for the DSAEK altered the outcomes in terms of VA, ECD, and surgical complications. The algorithm presented in this study is helpful in equally distributing benefits from thinner grafting for all DSAEK-operated patients.

A multivariate analysis and statistical model for predicting visual acuity and keratometry one year after cross-linking for keratoconus.

PURPOSE: To investigate putative prognostic factors for predicting visual acuity and keratometry 1 year following corneal cross-linking (CXL) for treating keratoconus. DESIGN: Prospective cohort study. METHODS: This study included all consecutively treated keratoconus patients (102 eyes) in 1 academic treatment center, with minimal 1-year follow-up following CXL. Primary treatment outcomes were corrected distance visual acuity (logMAR CDVA) and maximum keratometry (K(max)). Univariable analyses were performed to determine correlations between baseline parameters and follow-up measurements. Correlating factors (P ≤ .20) were then entered into a multivariable linear regression analysis, and a model for predicting CDVA and K(max) was created. RESULTS: Atopic constitution, positive family history, and smoking were not independent factors affecting CXL outcomes. Multivariable analysis identified cone eccentricity as a major factor for predicting K(max) outcome (ß coefficient = 0.709, P = .02), whereas age, sex, and baseline keratometry were not independent contributors. Posttreatment visual acuity could be predicted based on pretreatment visual acuity (ß coefficient = -0.621, P < .01, R(2) = 0.45). Specifically, a low visual acuity predicts visual improvement. A prediction model for K(max) did not accurately estimate treatment outcomes (R(2) = 0.15). CONCLUSIONS: Our results confirm the role of cone eccentricity with respect to the improvement of corneal curvature following CXL. Visual acuity outcome can be predicted accurately based on pretreatment visual acuity. Age, sex, and K(max) are debated as independent factors for predicting the outcome of treating keratoconus with CXL.

Does lamellar surgery for keratoconus experience the popularity it deserves?

PURPOSE: To analyse developments in surgical treatment for keratoconus (KC) by assessing rates and types of corneal surgery from 2005 to 2010. METHODS: The Dutch Transplantation Foundation supplied data on all keratoplasty procedures for KC performed from 2005 to 2010 in the Netherlands. Registration was carried out by the eyebank at allocation and by the surgeon at the time of surgery. The type of surgery was categorized as either a penetrating or a lamellar procedure. RESULTS: Five hundred and seventy-five anonymized records were received, with excellent data completion (99%). Patients undergoing penetrating surgery had on average a lower visual acuity, higher k-readings and were slightly older compared with the lamellar group. A previous corneal hydrops was recorded for 19.1% of patients. Regular penetrating keratoplasty decreased in popularity from 79.7% in 2005 to 43.7% in 2010, due to the increased rate of lamellar surgery (42.5% in 2010) and 'mushroom' penetrating keratoplasty (13.8% in 2010). When hydrops cases were excluded, popularity became equal (47.6% penetrating versus 52.4% lamellar surgery, in 2010). CONCLUSION: Lamellar surgery is gaining in popularity, although regular penetrating keratoplasty is still the more commonly performed procedure. Only when hydrops cases are excluded do transplant rates become comparable.

[Developments in corneal transplants: lamellar techniques emerging]. / Ontwikkelingen in corneatransplantatie: lamellaire technieken in opkomst.

Corneal transplants are the most frequently performed human transplant procedure. In the last decade, we have seen large developments in the field of corneal transplant surgery. Currently, several techniques are being used in the Netherlands, each with its own advantages and disadvantages and with distinct indications. In penetrating keratoplasty all layers of the cornea are replaced by a donor cornea. In so-called lamellar corneal transplantation only the affected layer of the cornea is replaced by donor tissue. The developments in corneal transplantation surgery have resulted in an improved prognosis in terms of vision and fewer complications.

Medical applications and outcomes of bitangential scleral lenses.

PURPOSE: To evaluate the clinical results of a new scleral lens design with a bitangential (nonrotationally symmetrical) periphery. METHODS: All the necessary data were obtained during the 1-year study period. The bitangential scleral lenses were fitted and monitored according to a standardized fitting methodology. They were cut by precise submicron lathing from high-oxygen-permeable materials (including 10 scleral lenses from Menicon Z material). Subjective performance, visual acuity, and scleral lens-fitting characteristics were recorded after a median of 9.4 weeks (range, 3 weeks to 1 year). RESULTS: Diagnoses in the 213 eyes (in 144 patients) were keratoconus (n = 121 eyes; 56.8%), ocular surface diseases (n = 31 eyes; 14.6%), penetrating keratoplasty (n = 29 eyes; 13.6%), and other forms of irregular astigmatism (n = 28 eyes; 13.1%). Many patients (164 lenses; 77.0%) gave high ratings for comfort. The most common diameter was 20.0 mm (162 lenses; 76.1%) (range, 18.5 to 21.5 mm). Median decimal best-corrected visual acuity with the bitangential scleral lenses was 0.8 (equivalent to Snellen 20/25) (range, 0 to 1.5). Most bitangential scleral lenses showed good fitting characteristics: optimal values were seen for lens movement (208 lenses; 97.7%) and lens position (208 lenses; 97.7%). Median central corneal clearance was 0.2 mm; clearances differed in the four peripheral directions. The median stabilization axis was 140 degrees (range, 0 to 180 degrees) in the right eyes and 60 degrees (range, 0 to 180 degrees) in the left eyes. CONCLUSIONS: The bitangential scleral lens-fitting and performance characteristics were clear and effective for the health professional and the patient. The high-oxygen-permeable material Menicon Z may, in theory, be of benefit to corneas with a high oxygen demand.

Cataract surgery in patients with nanophthalmos.

PURPOSE: To report the visual outcomes and complications of cataract surgery in a large series of patients with nanophthalmos. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Forty-three eyes with an axial length ≤ 20.5 mm of 32 adult patients who underwent cataract surgery in a tertiary clinic. METHODS: Medical records of patients undergoing cataract surgery between 1994 and 2010 were reviewed. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at 6 months after surgery and postoperative complications occurring during the entire follow-up period. RESULTS: Forty-three eyes of 32 patients (aged 19-87 years; median, 69 years) were included. Cataract surgery resulted in improvement of ≥ 3 Snellen lines in 19 eyes (44.2%). Two eyes (4.7%) lost ≥ 3 Snellen lines because of corneal decompensation in one and angle-closure glaucoma in the other. During the entire follow-up period, complications occurred in 12 eyes (27.9%). The most frequent complications were uveal effusion (9.3%) and cystoid macular edema (CME) (7.0%). CONCLUSIONS: Cataract surgery in patients with nanophthalmos remains a surgical challenge, and complications often occur in these high-risk eyes.

Corneal depositions in tyrosinaemia type I during treatment with Nitisinone.

We present a 17-year-old boy, diagnosed with tyrosinaemia type I at an age of 7 months, with new complaints of severe intermittent photophobia and burning eyes. His tyrosinaemia type I is treated with nitisinone and a protein-restricted diet. Dietary compliance is low since he entered puberty. His ocular complaints are attributable to subepithelial corneal deposits, resembling the common corneal phenotype of tyrosinaemia type II. Serum tyrosine levels were markedly elevated. Tyrosinaemia is a metabolic disease of tyrosine metabolism, subdivided into two types. Corneal deposits and photophobia are cardinal features of untreated tyrosinaemia type II, but not of type I. Novel treatment strategies (with nitisinone) for type I tyrosinaemia lead to a phenotype comparable with type II, including these corneal deposits. At follow-up visits his ocular complaints unfortunately remained unchanged, though he states his dietary compliance improved through the years.

Two cases of keratoconus diagnosed after pregnancy.

PURPOSE: This case report aims to demonstrate that pregnancy-induced biomechanical corneal changes in combination with risk factors for ectasia can develop into (the exacerbation of) keratoconus. CASE REPORT: We describe two women who were clinically diagnosed with keratoconus after their second pregnancy. Both women were myopic and had a history of allergies and contact lens wear. It is unclear whether these two women had a newly diagnosed keratoconus that developed during pregnancy or had experienced an exacerbation of an unrecognized, subclinical keratoconus. CONCLUSIONS: Nowadays, documented progression of keratoconus can be treated by corneal crosslinking to stabilize the weakened cornea. Therefore, it is important to understand the effects of hormonal changes in (keratoconic) eyes during pregnancy and to include topographic imaging in unexplained visual deterioration in young individuals, especially during or after a pregnancy.

Hearing disability in patients with Fuchs' endothelial corneal dystrophy: unrecognized co-pathology?

PURPOSE: To investigate a possible association between Fuchs' endothelial corneal dystrophy (FECD) and hearing disability. METHODS: A cross-sectional observational study was performed at the University Medical Center Utrecht. Cases and controls were patients who were treated by a cornea specialist between 2004 and 2008. FECD patients had either already undergone or were planned for a keratoplasty procedure. All controls were patients treated for cataract without any corneal pathology. Cases and controls were matched by age group and gender. A structured telephone interview combined with a validated self-perceived hearing function test (the Hearing Handicap Inventory for the Elderly, screening version; HHIE-S) was used for data collection. RESULTS: Hearing disability was reported in 33 patients (45.8%) in the FECD-group (n = 72, average age: 73 years) versus 50 patients (34.7%) in the control group (n = 144, average age: 73 years). Hearing disability was significantly associated with FECD after adjustment for age, noise exposure, and diabetes mellitus (odds ratio 1.97 95% confidence interval 1.04-3.75). CONCLUSION: This case-control study reports a significant association between FECD and hearing disability. The causal relation was not evaluated in this study, though mutations in the SLC4A11 gene could have played an important role. This gene encodes for an ion transporter, which has been found in the cornea and inner ear. With the lack of examination with a pure tone or speech audiometry in this study, further studies need to be performed in order to support the association and should include a complete ENT examination with audiometry and genetic research.

Corneal crosslinking for progressive keratoconus in four children.

The authors describe four children with progressive keratoconus treated by corneal crosslinking (CXL). The current CXL guidelines recommend treatment of patients 18 years and older. Nevertheless, keratoconus can rapidly progress in young teenagers. CXL could be a safe procedure to prevent a keratoplasty at a young age.