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Stefano Ranno1, Paolo Fogagnolo2, Luca Rossetti3, Nicola Orzalesi3, Paolo Nucci11Eye Clinic, San Giuseppe Hospital, University of Milan, Milan, Italy; 2GB Bietti Foundation for Study and Research in Ophthalmology, Rome, Italy; 3Eye Clinic, Department of Medicine, San Paolo Hospital, University of Milan, Milan, ItalyBackground: The purpose of this study was to evaluate corneal parameters in treated glaucoma patients, nontreated glaucoma patients, and normal subjects using confocal microscopy.Methods: Forty patients with primary open-angle glaucoma and 22 untreated controls underwent confocal microscopy of the cornea using the Heidelberg retinal tomograph cornea module. The glaucoma group was divided into two subgroups, ie, patients on medical treatment for at least two years before inclusion (with beta-blockers or prostaglandin analogs) and nontreated glaucoma patients. The following corneal parameters were evaluated: endothelial cell density and number, reflectivity, and tortuosity of sub-basal nerves. For reflectivity and tortuosity, a dedicated grading scale ranging from 0 to 4 was used. Differences between treatments were also evaluated in the treated glaucoma group.Results: Number of fibers and reflectivity of the sub-basal plexus were significantly lower in glaucoma patients as compared with controls (2.5 ± 0.7 versus 2.9 ± 0.9, P = 0.006, and 2.3 ± 0.8 versus 2.7 ± 0.9, P = 0.04, respectively), whereas tortuosity was significantly higher (2.6 ± 1 versus 2.0 ± 0.8, P = 0.007). Endothelial cell density (measured as cells per mm2) was lower in the glaucoma group comparing treated patients with nontreated patients (2826 ± 285 versus 3124 ± 272, P = 0.0003). Comparing treated patients with nontreated patients, relevant differences were found in number (2.3 ± 0.7 versus 2.8 ± 0.8, P = 0.004), tortuosity (2.8 ± 1 versus 2.2 ± 0.8, P = 0.004), and reflectivity (2.2 ± 0.8 versus 2.6 ± 0.8, P = 0.04). No differences in corneal parameters were found between beta-blockers and prostaglandin analogs.Conclusion: This study shows that differences in corneal parameters between glaucoma patients and controls may be due to the medical treatments used for glaucoma. These data should be taken into consideration in long-standing medical glaucoma treatment and in potential candidates for surgery.Keywords: cornea, glaucoma, sub-basal nerves, endothelial cells, confocal microscopy

Purpose: To assess reproducibility of central corneal thickness (CCT) measurement by means of ultrasonic pachymetry. Methods: Fifty one volunteers underwent three sessions of CCT measurements, each consisting of three CCT [...]

Aims To assess the testeretest variability of intraocular pressure (IOP) and ocular pulse amplitude (OPA) measurements utilising dynamic contour tonometry (DCT) and to evaluate possible influential factors. Methods The study included 350 consecutive subjects (175 glaucoma, 175 control; one eye per subject) from seven European centres. IOP was measured once with a Goldmann applanation tonometer (GAT) and twice by DCT (DCT1, DCT2) in a randomised sequence. OPA was also recorded for both DCT measurements. Differences (DCT1-DCT2; OPA1-OPA2; GAT-DCT1; GAT-DCT2) were assessed using the t test. The intraclass coefficient of correlation (ICC) and coefficient of variation (CoV) for DCT and OPA were calculated. Results DCT1 was 0.661.6 mmHg higher than DCT2 (p<0.001); OPA1 was 0.1±0.7 mm Hg higher than OPA2 (p=0.02). Results were not influenced by randomisation test order. In both glaucoma and normal subjects, DCT and OPA showed ICC>0.90 and >0.76, and CoV=4.8-5.0% and 10.3-10.5%, respectively. DCT1 and 2 were 2.4±2.6 and 1.8±2.6 mmHg higher respectively than GAT (p<0.001). Discussion DCT testeretest variability was almost perfect for IOP and good for OPA. Tonometry measurements with DCT tended to be overestimated compared with GAT. [ABSTRACT FROM AUTHOR]

Purpose: To compare the performance of Compass fundus automated perimetry (FAP) and Humphrey Field Analyzer (HFA) in glaucoma patients., Methods: A total of 120 patients with glaucoma underwent 1 FAP and 1 HFA perimetric test over the central 24° on one eye. The chosen eye and sequence were randomized and only reliable examinations were considered for analysis. Mean deviation (MD), pattern standard deviation (PSD), visual field index (VFI), and the area of absolute scotoma were compared between perimeters. Glaucoma Staging System (GSS2) data were analyzed by means of k test., Results: Mean sensitivity difference (FAP-HFA) was -1.0 ± 2.81 dB (p&lt;0.001, 95% confidence interval [CI] -1.61, -0.60 dB), MD difference was +0.27 ± 2.84 dB (p = 0.36, 95% CI -5.30, 5.83 dB), PSD difference was +0.48 ± 1.95 dB (p = 0.0075, 95% CI -3.37, 4.33 dB), and VFI difference was +2.4% ± 8.4% (p = 0.003, 95% CI -14.0%, +18.8% dB). Weighted kappa for GSS2 was 0.87. Points with null sensitivities were 9.9 ± 10.2 with FAP and 8.2 ± 8.9 with HFA (difference: 1.7 ± 4.0 points, p = 0.013)., Conclusions: Mean sensitivity with FAP is 1 dB lower than HFA, a finding due to different threshold strategies. Differences of global indices for FAP and HFA are small, which makes the 2 perimeters equivalent in the clinical setting. However, FAP seems more severe in evaluating glaucomatous damage, with absolute scotoma areas larger than with HFA. We raise the hypothesis that such difference may be the result of the active compensation of eye movements available with FAP.

Background: It is known that office-hour measurements might not adequately estimate IOP mean, peaks and fluctuations in healthy subjects. The purpose of the present study is to verify whether office-hour measurements in patients in different body positions can estimate the characteristics of 24-hour intraocular pressure (IOP) in treated POAG patients., Methods: The 24-hour IOP curves of 70 eyes of 70 caucasian patients with treated glaucoma were analyzed. Measurements were taken at 9 AM; 12, 3, 6, and 9 PM; and 12, 3, and 6 AM, both in the supine (TonoPen XL) and sitting (Goldmann tonometer) positions. The ability of five strategies to estimate IOP mean, peak and fluctuation was evaluated. Each method was analyzed both with regression of the estimate error on the real value and with "hit or miss" analysis., Results: The least biased estimate of the Peak IOP was obtained using measurements from both supine and sitting positions, also yielding the highest rate of correct predictions (which was significantly different from 3 of the remaining 4 strategies proposed, p < 0.05). Strategies obtained from the combination of supine, sitting and peak measurements resulted to be least biased for the Mean IOP and the IOP Fluctuation estimate, but all strategies were not found significantly different in terms of correct prediction rate (the only significant difference being between the two strategies based on sitting or supine measurements only, with the former being the one with the highest correct prediction rate)., Conclusions: The results of this study remark the concept that IOP is a dynamic parameter and that intensive measurement is helpful in determining its characteristics. All office-hour strategies showed a very poor performance of in correctly predicting the considered parameters within the thresholds used in this paper, all scoring a correct prediction rate below 52%.

Aims: To evaluate Compass, a new instrument for glaucoma screening and diagnosis that combines scanning ophthalmoscopy, automated perimetry, and eye tracking., Materials and Methods: A total of 320 human subjects (200 normal, 120 with glaucoma) underwent full ophthalmological evaluation and perimetric evaluation using the Humphrey SITA standard 24° test (HFA), and the Compass test that consisted of a full-threshold program on the central 24° with a photograph of the central 30° of the retina. A subgroup of normal subjects and glaucoma patients underwent a second Compass test during the same day in order to study test-retest variability. After exclusion of 30 patients due to protocol rules, a database was created to compare the Compass to the HFA, and to evaluate retinal image quality and fixation stability., Results: The difference in mean sensitivity between Compass and HFA was -1.02 ± 1.55 dB in normal subjects (p<0.001) and -1.01 ± 2.81 dB in glaucoma (p<0.001). Repeatability SD for the average sensitivity was 1.53 for normal subjects and 1.84 for glaucoma. Test time with the Compass was 634±96 s (607±78 for normals, 678±108 for glaucoma). Compass analysis showed the percentage of fixation within the central 1° was 86.6% in normal subjects, and 79.3% in glaucoma patients. Color image quality was sufficient for diagnostic use in >65% of cases; Image-based diagnosis was in accordance with the initial diagnosis in 85% of the subjects., Conclusions: Based on preliminary results, Compass showed useful diagnostic characteristics for the study of glaucoma, and combined morphological information with functional data.

Mutations in more than 60 different genes have been associated with non-syndromic and syndromic retinitis pigmentosa (RP), a heterogeneous group of inherited retinal dystrophies. To increase the understanding of the molecular epidemiology of the disease in Italy, we analyzed 56 patients with syndromic and non-syndromic forms of RP attending the Retinitis Pigmentosa Center of San Paolo Hospital (Milan, Italy). Patients underwent detailed clinical examination. Genomic DNA isolated from peripheral blood samples was screened for mutations in different genes according to RP form by direct sequencing analysis. The impact of novel missense mutations on protein functions was predicted by in silico analysis and protein sequence alignment. Cosegregation analysis was performed between available family members. Forty-one of the 56 probands analyzed had non-syndromic and 15 had syndromic RP forms. Putative disease-causing mutations were identified in 19 of 56 unrelated RP probands. Mutation screening identified a total of 22 different heterozygous variants. Notably, 12 of these putative pathogenic mutations have not been previously reported. New variants were found to be located on the USH2A, RPGR, EYS, and RHO genes. All 3 new variants detected in X-linked RP probands were confirmed in other affected family members. We found a positivity rate of 24.4% and 60% for probands with non-syndromic and syndromic RP, respectively. This is the first report of RPGR X-linked RP proband-ORF15 mutations in Italian patients with X-linked (XL)-RP. In addition, this is the first report of data regarding the association between EYS mutations and non-syndromic RP forms in the Italian population.

Purpose: To evaluate corneal subbasal layer changes after uneventful cataract surgery by means of in vivo confocal microscopy., Methods: This prospective study included 30 patients. Before surgery, and 1, 3, 6, 8 and 10 months after cataract surgery, all patients underwent a complete ophthalmological and confocal microscopy examination in the central and temporal corneal areas. Number of fibers, beading, tortuosity and reflectivity were analyzed., Results: Important changes were shown in the central cornea up to 3 months after surgery: a reduction in nerve fiber number (baseline: 4.4 ± 1.7; month 1: 1.2 ± 0.5, p < 0.0001; month 3: 2.5 ± 1.2, p < 0.005) and reflectivity (baseline: 3.6 ± 0.5; month 1: 1.4 ± 0.6, p < 0.0001; month 3: 1.9 ± 0.9, p < 0. 0001), and an increase in beading (baseline: 0.3 ± 0.5 beads/100 µm(2); month 1: 2.7 ± 0.6 beads/100 µm(2), p < 0.0001; month 3: 2.6 ± 0.5 beads/100 µm(2), p < 0. 0001). The confocal parameters completely progressively recovered thereafter (60% at 6 months, 87% at 8 and 10 months). The temporal plexus was absent at 1 month and fully recovered in all patients at month 8., Conclusion: Uneventful cataract surgery induces relevant corneal modifications when inspected by means of confocal microscopy., (© 2013 S. Karger AG, Basel.)

Purpose: To assess the therapeutic noninferiority of 0.005% latanoprost ophthalmic solution versus Xalatan in the treatment of patients with primary open-angle glaucoma or ocular hypertension., Patients and Methods: This was a double-masked, randomized, multicenter study. A total of 184 patients with a diagnosis of unilateral or bilateral primary open-angle glaucoma or ocular hypertension were randomly assigned to either 0.005% latanoprost ophthalmic solution or Xalatan for 12 weeks. The primary end-point was the change in intraocular pressure (IOP) at 12 weeks in the 2 groups. Noninferiority was reached if the 2-sided 95% confidence intervals (CI) for the difference between adjusted treatment means were entirely within the interval from -1.5 to +1.5 mm Hg., Results: The difference between treatments in the change of IOP from baseline to the end of treatment was 0.12 mm Hg (95% CI: -0.47, 0.71) in the intention-to-treat population and 0 mm Hg (95% CI: -0.58, 0.57) in the per protocol population. There was no statistically significant difference between the 2 groups in terms of drug-related adverse events. The most commonly reported drug-related local adverse events were: ocular hyperemia, eyelashes growth, and eye irritation., Conclusions: This study demonstrates that 0.005% latanoprost ophthalmic solution is noninferior to Xalatan in lowering IOP and is generally well tolerated.

Aims: To evaluate short- (ST) and long-term (LT) intraocular pressure (IOP) in patients with stable (SG) and progressive glaucoma (PG)., Materials and Methods: Fifty-two patients with treated glaucoma received a baseline 24-hour IOP curve and, every 6 months for 2 years, office-hour curve plus visual field test. Based on field changes, they were divided into 24 SG and 28 PG. ST and LT IOP mean, peak and fluctuation (standard deviation of measurements) were calculated. Parameters determining progression were evaluated by logistic regression., Results: At ST, SG and PG, respectively, had mean IOP of 16.8 ± 2.2 and 15.3 ± 1.8 mm Hg; peak of 19.7 ± 3.3, 17.4 ± 2.3 mm Hg; fluctuation of 2.3 ± 1.2, and 1.6 ± 0.6 mm Hg. LT parameters did not change in SG, whereas a significant increase of mean (+1.0 ± 1.5 mm Hg, p = 0.05), peak (2.0 ± 2.4 mm Hg, p = 0.0002), and fluctuation (0.5 ± 1.1 mm Hg, p = 0.008) occurred in PG. Mean, peak, and fluctuation were correlated, except mean and fluctuation in the long term. Association with progression was shown for change in mean IOP between ST and LT, and ST peak., Conclusions: SG and PG may show different IOP parameters when intensively measured at baseline and follow-up. Mean IOP change between ST and LT periods and ST peak were the parameters associated with progression., (Copyright © 2013 S. Karger AG, Basel.)

Purpose: To evaluate the postoperative effects of topical coenzyme Q(10) + vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate (CoQ(10)) after cataract surgery., Methods: 40 consecutive patients were randomized to receive CoQ(10) or saline solution (SS) twice daily for 9 months after uneventful cataract surgery with a temporal port. Before surgery, on day 14 and at months 3, 6 and 9, they underwent non-invasive break-up time (NIBUT) testing, Schirmer test, BUT, aesthesiometry as well as in vivo confocal microscopy of the subbasal nerve plexus of the cornea (SBP). The density of the subbasal nerves was calculated in the central (CFD) and temporal (TFD) cornea (number of fibres per field)., Results: On day 14, surgery reduced CFD and TFD, respectively, by 25-35 and 50%; indices of ocular surface stability were all impaired. The treatment with CoQ(10) was associated with faster nerve regeneration than SS (at month 3, CFD +1.5 ± 1.9 vs. +0.2 ± 1.8, p = 0.04, and TFD +2.5 ± 1.7 vs. +1.0 ± 1.6, p = 0.007; at month 6, TFD +2.7 ± 1.9 vs. +1.4 ± 1.5, p = 0.02) and better stability of ocular surface (NIBUT and BUT) throughout the study. No relevant side effects were found, apart from occasional burning in 10% of CoQ(10) patients., Conclusions: Changes of the corneal nerves occurring after cataract surgery may influence the integrity of the ocular surface. Treatment with topical CoQ(10) has a positive effect in restoring SBP anatomy and ocular surface stability., (Copyright © 2012 S. Karger AG, Basel.)

Purpose: To report an advanced case of Terrien marginal corneal degeneration (TMD) analyzed by means of confocal microscopy., Methods: A 62-year-old woman with TMD underwent a routine ophthalmological examination and was evaluated for the disease by using in vivo laser scanning confocal microscopy with the Heidelberg Retina Tomograph 2 Rostock Cornea Module., Results: The slit-lamp examination of the right eye showed an upper peripheral cornea thinning associated with a deposition of refractile yellow-white materials in the anterior stroma. Superficial radial vessels in the upper peripheral cornea were the only pathological findings of the left eye. Confocal microscopy of the right eye lesion showed deposition of hyperreflective material, and the stroma below presented a honeycomb-like pattern. Inflammatory cell infiltration, abnormal subbasal nerve plexus, epithelial basal membrane defects, irregular Bowman membrane, and the presence of activated keratocytes were observed in the cornea of both eyes., Conclusions: In vivo confocal microscopy can detect subtle corneal changes in an advanced case of TMD, which may be signs of subclinical inflammation.

Purpose: To evaluate the corneal changes of patients with Crohn's disease (CD) using confocal microscopy and to investigate the association among confocal parameters and CD activity and CD treatment., Methods: Thirty consecutive patients (age: 42 ± 12 years; 19 women and 11 men) affected by CD and 30 control eyes (age matched and gender matched) underwent an ophthalmic examination and, in 1 eye chosen at random, confocal microscopy of the central cornea using the cornea module of Heidelberg Retina Tomograph. The following confocal parameters were evaluated: density of basal epithelial cells, epithelial dendritic cells, anterior and posterior stromal keratocytes, and endothelial cells; the subbasal plexus was assessed for number and tortuosity of the nerve fibers., Results: Routine ophthalmic evaluation was normal in the whole population. At confocal microscopy, 40% of patients with CD had hyperreflective dots in the basal epithelium, which were absent in the control group. Activation of keratocytes was found in 86.6% of patients with CD and was absent in the control group. Compared with controls, patients with CD had lower density of dendritic cells (12.2 ± 26.3 vs. 50.3 ± 37.6 cells per square millimeter; P = 0.001). The other confocal parameters were similar in the 2 groups. No correlation between CD activity index and confocal changes was found., Conclusion: Confocal microscopy can detect subtle corneal changes in patients with CD, which may be signs of subclinical inflammation.

Aim: To evaluate the long-term perimetric fluctuation (LF) in patients with different stages of glaucoma according to the Glaucoma Staging System 2 (GSS2)., Methods: This multicentre retrospective study included 161 eyes of 161 stable glaucoma patients undergoing four visual-field tests (Humphrey SITA-Standard program over the central 24° or 30°) over a 2-year period. For each patient, the stage of the disease was classified according to GSS2. LF was then calculated as the mean of the standard deviations of point-to-point threshold sensitivities in the four repetitions. LF in GSS2 stages was compared using the t test. Results LF progressively increased from stage 0 to stage 4, and then decreased at stage 5. Stage 4 had a peak of 3.19 ± 0.94 dB, with statistically significant differences compared with all the other stages. The lowest LF (1.65 ± 0.60 dB) was found for normal subjects, whereas similar data were found for borderline patients and those at stages 1 and 5 (2.09 ± 0.58, 2.13 ± 0.57 and 2.22 ± 0.89 dB, respectively; p > 0.13). Visual fields with generalised defects had a lower LF (1.90 ± 0.81) than those with mixed (2.84 ± 0.87, p = 0.0003) and localised (2.63 ± 0.72, p = 0.004) defects. Conclusions In this study, the authors showed that the lower the visual-field defect, the lower was LF, except at stage 5 of GSS2. As test-retest changes exceeding LF could represent a sign of progression, the authors suggest that clinicians using this classification system calculate LF, in order to better differentiate true progression from variability.

Purpose: To evaluate the diagnostic assessment of optic nerve heads (ONH) by stereophotography (SP) and Heidelberg retina tomograph (HRT) in patients with retinitis pigmentosa (RP)., Methods: This study involved 53 consecutive patients with RP and 24 controls who underwent ONH examination by SP and HRT. On the basis of the appearance at SP, RP ONH were divided in normal-colored (24/53) and pale (29/53). The measurements of vertical ONH diameter and vertical cup/disc ratio (VCDR) by SP and HRT were compared between the groups by means of t test and Bland-Altman plots. Diagnosis, ONH pallor and size, HRT image quality (image standard deviation, SD) were also inspected as sources of differences in the results by means of a multivariate analysis., Results: Vertical diameter measurements were similar using SP and HRT, respectively (1.93±0.50 and 1.80±0.62 for normal-colored ONH, P=0.43; 2.02±0.65 and 1.90±0.40 for pale ONH, P=0.27; and 1.98±0.55 and 1.84±0.52 for controls, P=0.33). In normal-colored ONH, VCDR was 0.30±0.11 at SP and 0.31±0.21 at HRT (P=0.90); in controls, it was 0.29±0.13 at SP and 0.30±0.18 at HRT (P=0.77). In the group with pale ONH, VCDR was 0.34±0.14 at SP and 0.53±0.24 at HRT (P<0.001). HRT image quality was the only parameter which influenced the difference in VCDR estimates between SP and HRT (P=0.02). In patients with pale ONH, this difference was significantly higher, when images of acceptable quality were used for analysis (0.36±0.15 vs. 0.15±0.21 for images with good quality or better, P=0.03)., Conclusions: In ONH diseases other than glaucoma, HRT may give misleading information when images of acceptable quality are considered for analysis. We therefore recommend the use of images with good quality or better (SD ≤30 μm) in these cases.