Ugo de Sanctis

Sensitivity and Specificity of Posterior Corneal Elevation Measured by Pentacam in Discriminating Keratoconus/Subclinical Keratoconus

PURPOSE To estimate the sensitivity and specificity of posterior elevation in discriminating keratoconus and subclinical keratoconus from normal corneas. DESIGN Prospective case-control study. PARTICIPANTS Seventy-five patients with keratoconus, 25 with subclinical keratoconus, and 64 refractive surgery candidates with normal corneas. METHODS In one eye of each patient, posterior corneal elevation was measured in the central 5 mm using the Pentacam rotating Scheimpflug camera (Oculus, Wetzlar, Germany). Posterior corneal elevation in keratoconus and subclinical keratoconus were compared with that in normal corneas in separate analyses. Receiver operating characteristic (ROC) curves were used to determine the tests overall predictive accuracy (area under the curve) and to identify optimal posterior corneal elevation cutoff points to maximize sensitivity and specificity in discriminating keratoconus and subclinical keratoconus from normal corneas. Logistic regression was used to support cutoff points identified through ROC curve analysis, and to check for model validity; model goodness-of-fit was estimated using r(2), and its internal validation was by bootstrapping analysis. MAIN OUTCOME MEASURES Posterior corneal elevation in keratoconus, subclinical keratoconus, and normal corneas. RESULTS Mean posterior corneal elevation was statistically higher in keratoconus (100.7+/-49.2 microm; P<0.001), and subclinical keratoconus (39.9+/-15.0 microm; P = 0.01) versus normal corneas (19.8+/-6.37 microm). ROC curve analyses showed high overall predictive accuracy of posterior elevation for both keratoconus and subclinical keratoconus (area under the curve 0.99 and 0.93, respectively). Optimal cutoff points were 35 microm for keratoconus and 29 microm for subclinical keratoconus. These values were associated with sensitivity and specificity of 97.3% and 96.9%, respectively, for keratoconus, and 68% and 90.8% for subclinical keratoconus. Similar cutoff points were obtained with logistic regression analysis (38 microm for keratoconus and 32 microm for subclinical keratoconus). The models showed good fit to the data, including after internal validation. CONCLUSIONS Posterior corneal elevation very effectively discriminates keratoconus from normal corneas. Its efficacy is lower for subclinical keratoconus, and thus data concerning posterior elevation should not be used alone to stratify patients with this condition.

SOX2 anophthalmia syndrome

Heterozygous, de novo, loss‐of‐function mutations in SOX2 have been shown to cause bilateral anophthalmia. Here we provide a detailed description of the clinical features associated with SOX2 mutations in the five individuals with reported mutations and four newly identified cases (including the first reported SOX2 missense mutation). The SOX2‐associated ocular malformations are variable in type, but most often bilateral and severe. Of the nine patients, six had bilateral anophthalmia and two had anophthalmia with contralateral microphthalmia with sclerocornea. The remaining case had anophthalmia with contralateral microphthalmia, posterior cortical cataract and a dysplastic optic disc, and was the only patient to have measurable visual acuity. The relatively consistent extraocular phenotype observed includes: learning disability, seizures, brain malformation, specific motor abnormalities, male genital tract malformations, mild facial dysmorphism, and postnatal growth failure. Identifying SOX2 mutations from large cohorts of patients with structural eye defects has delineated a new, clinically‐recognizable, multisystem disorder and has provided important insight into the developmental pathways critical for morphogenesis of the eye, brain, and male genital tract.

Corneal endothelium evaluation with 2 noncontact specular microscopes and their semiautomated methods of analysis.

Purpose: Noncontact specular microscopes and semiautomated methods of endothelial analysis are widely used in the clinical practice and for research purposes. In this study, the interexaminer reproducibility between two noncontact specular microscopes using different semiautomated methods was assessed in normal corneas. Methods: Average cell size (ACS), endothelial cell density (ECD), coefficient of variation (CV), and hexagonality values were independently calculated by two examiners with the Topcon SP 2000P Image-NET retraced method and the Konan CC7000 center method in 49 normal subjects. Interexaminer reproducibility and correlation between instruments/methods were assessed through 95% limits of agreement, intra-class correlation coefficient (ICC), Pearson correlation coefficient, and Spearman rank test. Results: Interexaminer reproducibility was good for ACS and ECD measurements (ICC> 0.85) but weak for CV and hexagonality (ICC < 0.65). Significantly higher ACS and lwer ECD values (P <0.05) were obtained with the Topcon in comparison with the Konan method by both examiners. ACS and ECD mean differences were respectively, +26&mgr;m2 and −184 cell/mm2 for examiner 1 and +36&mgr;m2 and −228 cell/mm2 for examiner 2. No significant difference (P > 0.05) between instruments/methods was found in CV or hexagonality values; however, the correlation for these parameters was low (r < 0.20). Conclusions: Either instrument or method allows reproducible and accurate ACS and ECD measurements on normal corneas, but the difference between the two instruments is systematic and significant. The difference found were not clinically meaningful however for research/longitudinal study purposes, the data collected with the two systems cannot be used interchangeably.

Evaluation of Serotonin Levels in Human Aqueous Humor

Purpose: Serotonin is biochemically present in the iris and ciliary body of animals and humans. Controversial findings are reported about the concentrations of serotonin in aqueous humor with respect to plasma in humans. The aim of this study was to evaluate the levels of serotonin both in aqueous humor and plasma in human subjects. Methods: In 50 patients with glaucoma or cataract, plasma and aqueous humor serotonin levels were measured by HPLC with electrochemical detection. Serotonin plasma levels were also measured in 25 healthy subjects as controls. Results: In all patients with cataract or glaucoma, the aqueous humor serotonin concentration is significantly lower than that in plasma [1.14±0.29 (SEM) vs. 5.33±1.03 ng/ml, p < 0.01]. Furthermore, in the same patients and in 25 healthy controls, serotonin plasma levels were similar. Conclusion: Our study shows that serotonin is present in human aqueous humor and its concentration is 4 times lower than in plasma.

In Vivo Confocal Microscopic Evaluation of Corneal Langerhans Cells in Dry Eye Patients

Purpose. To assess inflammatory involvement of cornea in dry eye by means of confocal microscopy, evaluating the presence and distribution of Langherans cells (LCs). Methods: 98 eyes of 49 subjects were enrolled: 18 subjects affected by Sjögren Syndrome Dry Eye (SSDE), 17 with Non-Sjögren Syndrome Dry Eye (NSSDE), 14 healthy volunteeers. Dry eye symptoms, tear film, ocular surface damage and corneal confocal microscopy were analized. Results: A significant increase of LCs density was observed at sub-basal nerve plexus (SSDE = 79 cells/mm2 andNDE = 22 cells/mm2; p = 0,0031) and sub-epithelial nerve plexus (SSDE = 38 cells/mm2 and NDE = 3 cells/mm2; p = 0,0169) in central cornea of SSDE group. An increased number of LCs from the center to the periphery of the cornea was observed, significant only in healthy volunteers group. In dry eye patients there was an increase in LCs density in both peripheral and central cornea with a significant difference between NDE (14,66 cells/mm2) and SSDE (56,66 cells/mm2) only in central cornea (p = 0,0028). In SSDE group, mean density of LCs in central cornea results also superior to NSSDE group (29,33 cells/mm2). There was no correlation between LCs density and dry eye symptoms, tear film deficiency and ocular surface damage. Conclusion: This study demonstrates the activation of an inflammatory and immunological reaction in cornea of NSSDE and SSDE patients. Confocal microscopy can be an important diagnostic tool in evaluation and follow-up of dry eye disease.

Phacoemulsification and customized toric intraocular lens implantation in eyes with cataract and high astigmatism after penetrating keratoplasty

UNLABELLED Phacoemulsification and implantation of a hydrophilic acrylic toric intraocular lens (IOL) (T-flex 623T) with customized cylindrical power was performed in 1 eye in 3 consecutive patients with cataract and high postkeratoplasty astigmatism (range 6.75 to 8.75 diopters [D]). Twelve months postoperatively, the uncorrected distance visual acuity improved from 20/200 to 20/30 in Case 1, from 20/400 to 20/40 in Case 2, and from 20/200 to 20/25 in Case 3 and the corrected distance visual acuity was 20/25 or better in all 3 eyes. The spheroequivalent was within ± 0.50 D of the intended value and the refractive astigmatism was less than 1.00 D. The corneal grafts were transparent, and the endothelial cell loss range was 6% to 12%. Rotation of the toric IOL was less than 5 degrees. The toric IOL with customized cylindrical power provided good postoperative rotational stability and very satisfactory postoperative visual recovery. This type of toric IOL is appropriate to correct high postkeratoplasty astigmatism in eyes operated on for cataract. FINANCIAL DISCLOSURE No author has a financial or proprietary interest in any material or method mentioned.

Refractive Error after Cataract Surgery Combined with Descemet Stripping Automated Endothelial Keratoplasty

PURPOSE To assess refractive error after cataract surgery combined with Descemet stripping automated endothelial keratoplasty using adjusted keratometric (K) readings to calculate intraocular lens (IOL) power. DESIGN Prospective, interventional case series. METHODS One eye of 39 consecutive patients with Fuchs endothelial dystrophy and cataract were included. To calculate IOL power before surgery, the Javal steep and flat K readings (Haag-Streeit) were adjusted by reducing their value by -1.19 diopters (D); the axial length was measured by immersion biometry, and the standard A-constant was used. Surgery included phacoemulsification, IOL (Acrysof SN60AT; Alcon) implantation within the capsular bag, and Descemet stripping automated endothelial keratoplasty using posterior lamella prepared with a 300-μm head microkeratome (Moria). The absolute prediction error (absolute difference between predicted and achieved refraction) was assessed 6 months after surgery. RESULTS The mean power of the implanted IOL was 23.22 ± 2.90 D. The mean predicted and achieved refractions were -0.27 ± 0.26 D and -0.23 ± 0.73 D, respectively. The mean absolute prediction error was 0.59 ± 0.42 D (range, 0.05 to -1.52 D). The postoperative spherical equivalent fell within ±0.50 D, ±1.00 D, and ±2.00 D of the predicted refraction in 55.5%, 83.3%, and 100% of cases, respectively. Had the IOL power been calculated without adjusting the K readings, the mean absolute prediction error would have been significantly higher (0.86 ± 0.62 D; P = .04). CONCLUSIONS In this study, in which posterior lamellae were prepared using a 300-μm head microkeratome, adjusting preoperative K readings by -1.19 D led to accurate IOL power calculation and highly predictable refractive error after cataract surgery combined with Descemet stripping automated endothelial keratoplasty.

Treatment for neovascular age related macular degeneration: The state of the art.

With the introduction in the clinical practice of drugs inhibiting vascular endothelial growth factor (VEGF) the visual outcomes of patients with neovascular age related macular degeneration (AMD) dramatically improved. Since 2006 repeated intravitreal injections of anti-VEGF became the standard of care for the treatment of neovascular AMD. This review provides an overview of available data form clinical trials supporting the use of anti-VEGF molecules for the treatment of this condition. Several questions remain open, in particular the regimen of treatment, the frequency of injection, the safety of the different drugs, and the poor response to the treatment in some cases. Therefore, new agents and alternative delivery are currently under evaluation.

Changing trends in corneal graft surgery: A ten-year review

AIM To review indications and corneal tissue use for penetrating and lamellar surgery between 2002 and 2011. METHODS The surgical reports of corneal grafts performed during 2002-2011, using tissues supplied by the Eye Bank of Piedmont (Italy), were reviewed retrospectively. Patient demographic data, date of intervention, indication for surgery, and surgical technique used were recorded. Surgical techniques included penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK). The χ (2) test was used to compare the distribution of indications and types of surgical technique used, for corneal grafts done during 2002-2006 versus those done during 2007-2011. RESULTS The number of corneal grafts increased by 30.7% from 2002-2006 to 2007-2011 (from 1567 to 2048). Comparing the two periods, both main indications and surgical techniques changed significantly. In 2007-2011, the proportion of interventions for aphakic/pseudophakic bullous keratopathy (from 16.8% to 21.3%), graft failure (from 16.4% to 19.1%) and Fuchs endothelial dystrophy (from 12.8% to 16.7%) all increased significantly (P<0.05), while those for keratoconus decreased significantly (from 35.6% to 27.3%; P<0.001). In 2007-2011, the proportion of PK decreased significantly (from 92.4% to 57.2%; P<0.001) while that of EK and DALK went from 0.4% to 30.2% (P<0.001) and from 7.2% to 12.6% (P<0.001) respectively. CONCLUSION During 2002-2011 the number of interventions increased significantly for corneal endothelial diseases and graft failure. The growing demand for interventions for these diseases corresponded to the widespread adoption of EK techniques. The use of DALK also increased, but more moderately than EK procedures.

Wave-like opacities at the interface after descemet stripping automated endothelial keratoplasty.

Purpose: To describe a peculiar postoperative complication of Descemet stripping automated endothelial keratoplasty (DSAEK), characterized by wave-like opacities at the donor–recipient interface. Methods: Wave-like opacities at the interface were observed a few days after surgery, in 1 eye of 2 patients who had undergone uneventful DSAEK for Fuchs endothelial dystrophy. DSAEK was performed using microkeratome-prepared lamellar grafts obtained from organ culture–preserved corneas. In the recipient, the 8.50-mm graft was inserted using a pull-through technique. Postoperative follow-up was 12 months in case 1 and 6 months in case 2. Results: The wave-like opacities were whitish and involved the central cornea in both cases; in case 2, they were associated with hyperreflective dots. Despite intensive topical therapy with dexamethasone 0.2%, the opacities at the interface persisted during follow-up. However, visual acuity progressively improved; at last examination, uncorrected and corrected distance visual acuity were, respectively, 20/40 and 20/25 in case 1 and 20/30 and 20/20 in case 2. Optical coherence tomography showed that the interface reflectivity was slightly higher than it was in DSAEK cases without opacities. The central thickness of the whole cornea and the lamella were 563 and 93 &mgr;m in case 1 and 603 and 140 &mgr;m in case 2. Postoperative endothelial cell loss was 37% in case 1 and 24% in case 2. Conclusions: Wave-like opacities at the donor–recipient interface are a rare complication of DSAEK surgery of unclear origin. Although interface opacities involve the central cornea and persist after surgery, good postoperative visual recovery can be achieved.