Federico Grignolo

Photodynamic Therapy for Chronic Central Serous Chorioretinopathy

Purpose To determine whether photodynamic therapy (PDT) is effective for treatment of chronic central serous chorioretinopathy (CSC). Methods Sixteen eyes with chronic CSC and macular detachment documented by optical coherence tomography (OCT) received PDT guided by indocyanine green (ICG) angiography according to the parameters outlined in the TAP Study. One or more laser spots were applied to the areas of choroidal vascular hyperpermeability that corresponded to retinal pigment epithelium decompensation. Patients were observed for 6 to 12 months. Two PDT sessions 1 month apart were performed on 2 eyes. Examinations included visual acuity measurement, fundus biomicroscopy, fluorescein and ICG angiography, and OCT. Results Macular exudation resolved completely in 13 eyes (81%) and partially regressed in 3. Choriocapillaris hypoperfusion was shown by ICG angiography for several months at the site of PDT application. Visual acuity improved 1 to 4 lines in 11 eyes and was unchanged in 5 eyes. Conclusions ICG-guided PDT performed according to the parameters outlined by the TAP Study seems effective for treating chronic CSC. Further studies are needed to verify treatment safety and the time and rate of recurrences.

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.

Hypertensive retinopathy revisited: some answers, more questions

Hypertension is associated with cardiovascular risk and systemic target organ damage. Retinopathy is considered one of the indicators of target organ damage. This review focuses on recent studies on hypertensive retinopathy and their implications for clinical care. Early recognition of hypertensive retinopathy signs remains an important step in the risk stratification of hypertensive patients.

Ganglion cell complex and retinal nerve fiber layer measured by fourier-domain optical coherence tomography for early detection of structural damage in patients with preperimetric glaucoma.

Aims To evaluate the capability of Fourier-domain optical coherence tomography (FD-OCT) to detect structural damage in patients with preperimetric glaucoma. Methods A total of 178 Caucasian subjects were enrolled in this cohort study: 116 preperimetric glaucoma patients and 52 healthy subjects. Using three-dimensional FD-OCT, the participants underwent imaging of the ganglion cell complex (GCC) and the optic nerve head. Sensitivity, specificity, likelihood ratios, and predictive values were calculated for all parameters at the first and fifth percentiles. Areas under the curves (AUCs) were generated for all parameters and were compared (Delong test). For both the GCC and the optic nerve head protocols, the OR logical disjunction (Boolean logic operator) was calculated. Results The AUCs didn’t significantly differ. Macular global loss volume had the largest AUC (0.81). Specificities were high at both the fifth and first percentiles (up to 97%), but sensitivities were low, especially at the first percentile (55%–27%). Conclusion Macular and papillary diagnostic accuracies did not differ significantly based on the 95% confidence interval. The computation of the Boolean OR operator has been found to boost diagnostic accuracy. Using the software-provided classification, sensitivity and diagnostic accuracy were low for both the retinal nerve fiber layer and the GCC scans. FD-OCT does not seem to be decisive for early detection of structural damage in patients with no functional impairment. This suggests that there is a need for analysis software to be further refined to enhance glaucoma diagnostic capability.

Magnetic resonance imaging and Orbscan assessment of the anterior chamber

PURPOSE: To evaluate the correlation between white‐to‐white (WTW) distance as assessed by Orbscan II (Bausch & Lomb) and high‐resolution magnetic resonance imaging (MRI) sulcus–sulcus (S–S) measures and to analyze the correlation between age and anterior chamber parameters. SETTING: Istituto per la Ricerca e la Cura del Cancro, Candiolo, Torino, Italy. METHODS: Eighty‐eight patients had MRI with a 1.5 Tesla imager (GE Medical Systems) using a 3‐inch circular coil. T1 weighted fast spin‐echo scans were performed on the axial plane. Orbscan II was also used to measure WTW distance, K, anterior chamber depth (ACD), and lens curvature. One eye was randomly selected for analysis. Measures were compared using Spearman correlation, paired Student t test, and analysis of variance (ANOVA; post hoc: Scheffé). Intersession variability was performed in 10 patients. Ten MRI images were randomly selected and measured by 2 operators in a masked fashion (intrasession variability). RESULTS: Intersession and intrasession correlation was good for MRI (r = 0.89 and r = 0.92, respectively), and intersession was good for Orbscan (r = 0.91). When comparing Orbscan II and MRI results, the ACD was well correlated and not significantly different, whereas the S–S and the WTW measures were not correlated and significantly different. Lens thickness and lens diameter were directly correlated with age; S–S, WTW, lens curvature, and ACD were inversely correlated with age. CONCLUSIONS: Current methods of measuring the WTW were poorly correlated with anatomical measures. The S–S diameter and other anterior chamber structures significantly change with age, which could give rise to potential problems with posterior chamber phakic intraocular lens sizing position.

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.

Recent developments in the management of dry age-related macular degeneration

Dry age-related macular degeneration (AMD), also called geographic atrophy, is characterized by the atrophy of outer retinal layers and retinal pigment epithelium (RPE) cells. Dry AMD accounts for 80% of all intermediate and advanced forms of the disease. Although vision loss is mainly due to the neovascular form (75%), dry AMD remains a challenge for ophthalmologists because of the lack of effective therapies. Actual management consists of lifestyle modification, vitamin supplements, and supportive measures in the advanced stages. The Age-Related Eye Disease Study demonstrated a statistically significant protective effect of dietary supplementation of antioxidants (vitamin C, vitamin E, beta-carotene, zinc, and copper) on dry AMD progression rate. It was also stated that the consumption of omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, has protective effects. Other antioxidants, vitamins, and minerals (such as crocetin, curcumin, and vitamins B9, B12, and B6) are under evaluation, but the results are still uncertain. New strategies aim to 1) reduce or block drusen formation, 2) reduce or eliminate inflammation, 3) lower the accumulation of toxic by-products from the visual cycle, 4) reduce or eliminate retinal oxidative stress, 5) improve choroidal perfusion, 6) replace/repair or regenerate lost RPE cells and photoreceptors with stem cell therapy, and 7) develop a target gene therapy.

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.

Micropulse diode laser trabeculoplasty (MDLT): A phase II clinical study with 12 months follow-up

Objective This pilot study evaluates the pressure lowering potential of subthreshold micropulse diode laser trabeculoplasty (MDLT) for a clinically meaningful duration in patients with medically uncontrolled open angle glaucoma (OAG). Design prospective interventional case series. Participants Thirty-two eyes of 20 consecutive patients with uncontrolled OAG (12 bilateral and 8 unilateral). Methods Confluent subthreshold laser applications over the inferior 180° of the anterior TM using an 810 nm diode laser in a micropulse operating mode. The intraocular pressure (IOP) was measured at baseline and at 1 hour, 1 day, 1 week, 3, 6, 9, and 12 months post-treatment. Flare was measured with a Kowa FM 500 flare-meter at baseline and at 3 hours, 1 day, 1 week, and 12 months post-treatment. After treatment, the patients were maintained on their pre-treatment drug regimen. Main outcome measures Criteria for treatment response were IOP reduction ≥3 mm Hg and IOP ≤21 mm Hg within the first week after MDLT. Eyes not complying to the above criteria during the follow-up were considered treatment failure. Mean IOP change and percentage of IOP reduction during the follow-up were calculated. Results One eye was analyzed for bilateral patients. A total of 20 eyes were thus included. Four eyes (20%) did not respond to treatment during the first week. One additional eye failed at the 6 month visit. The treatment was successful in 15 eyes (75%) at 12 months. The IOP was significantly lower throughout follow-up (p < 0.01). At 12 months, the mean percentage of IOP reduction in the 15 respondent eyes was 22.1% and 12 eyes (60%) had IOP reduction higher than 20%. During the first two postoperative days, one eye with pigmentary glaucoma experienced a significant increase of flare associated with an IOP spike (34 mm Hg) that was controlled with systemic drugs; afterwards it qualified as a respondent and completed the study. No increase of flare was found in any other patient. No peripheral anterior synechiae formed. Conclusions In this case series, MDLT was effective in reducing IOP in 75% of medically insufficiently controlled OAG eyes without significant complications. This justifies randomized clinical studies to compare MDLT with current IOP lowering strategies.

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.