Giacomo Savini

Correlation between retinal nerve fibre layer thickness and optic nerve head size: an optical coherence tomography study

Aim: To investigate the correlation between retinal nerve fibre layer (RNFL) thickness and optic nerve head (ONH) size in normal white subjects by means of optical coherence tomography (OCT). Methods: 54 eyes of 54 healthy subjects aged between 15 and 54 underwent peripapillary RNFL thickness measurement by a series of three circular scans with a 3.4 mm diameter (Stratus OCT, RNFL Thickness 3.4 acquisition protocol). ONH analysis was performed by means of six radial scans centred on the optic disc (Stratus OCT, Fast Optic Disc acquisition protocol). The mean RNFL values were correlated with the data obtained by ONH analysis. Results: The superior, nasal, and inferior quadrant RNFL thickness showed a significant correlation with the optic disc area (R = 0.3822, p = 0.0043), (R = 0.3024, p = 0.026), (R = 0.4048, p =  0.0024) and the horizontal disc diameter (R = 0.2971, p = 0.0291), (R = 0.2752, p = 0.044), (R = 0.3970, p = 0.003). The superior and inferior quadrant RNFL thickness was also positively correlated with the vertical disc diameter (R = 0.3774, p = 0.0049), (R = 0.2793, p = 0.0408). A significant correlation was observed between the 360° average RNFL thickness and the optic disc area and the vertical and horizontal disc diameters of the ONH (R = 0.4985, p = 0.0001), (R = 0.4454, p = 0.0007), (R = 0.4301, p = 0.0012). Conclusions: RNFL thickness measurements obtained by Stratus OCT increased significantly with an increase in optic disc size. It is not clear if eyes with large ONHs show a thicker RNFL as a result of an increased amount of nerve fibres or to the shorter distance between the circular scan and the optic disc edge.

The challenge of dry eye diagnosis

The currently available methods for the diagnosis of dry eye are still far from being perfect for a variety of reasons. This review attempts to highlight the advantages and disadvantages of both traditional tests (such as Schirmer’s test, break-up time and ocular surface staining) and innovative noninvasive procedures, including tear meniscus height measurement, corneal topography, functional visual acuity, tear interferometry, tear evaporimetry and tear osmolarity assessment.

Natural History of Leber's Hereditary Optic Neuropathy: Longitudinal Analysis of the Retinal Nerve Fiber Layer by Optical Coherence Tomography

PURPOSE To investigate by optical coherence tomography (OCT) the topographic pattern and temporal sequence of fiber loss in the peripapillary retinal nerve fiber layer (RNFL) of patients with Lebers hereditary optic neuropathy (LHON) in a longitudinal follow-up. DESIGN Cohort study. PARTICIPANTS Six eyes of 4 patients with molecularly defined LHON were enrolled before the subacute period of visual loss. METHODS Subjects were studied by StratusOCT (Carl Zeiss Meditec, Inc., Dublin, CA) during a 9-month follow-up starting from the presymptomatic stage of the disease. Examinations were carried out at 4 different time points: presymptomatic stage, time of visual loss, and 3 and 9 months later. MAIN OUTCOME MEASURES Peripapillary RNFL thickness for each quadrant of the optic nerve. Statistical comparisons were performed by ordinary analysis of variance with Dunnetts post-test. RESULTS A significant increase of RNFL thickness was detected in the temporal and inferior quadrants between the presymptomatic stage and the disease onset (P<0.05). The 360-degree average and the superior and nasal quadrants showed a nonstatistically significant increase of thickness at this time. In the 360-degree average (P<0.01), superior (P<0.01), nasal (P<0.05), and inferior (P<0.01) quadrants, RNFL thickening showed statistically significant changes between the presymptomatic stage and the 3-month follow-up. At 3 months, a nonsignificant reduction of RNFL thickness was detected in the temporal quadrant. A significant reduction of RNFL was detected in all but the nasal quadrants between the presymptomatic stage and the 9-month Follow-up. CONCLUSIONS The RNFL thickness increase first appeared at the temporal and inferior quadrants. Conversely, at 3 months the thickening fibers were more evident in the superior and nasal quadrants. These findings are consistent with the established preferential early involvement of the papillomacular bundle in LHON. We also demonstrated the previously unrecognized simultaneous early involvement of the inferior quadrant. The late involvement of both superior and nasal quadrants suggests a dynamic evolution of the acute stage that continues for 3 months and may represent a therapeutic window of opportunity.

The influence of axial length on retinal nerve fibre layer thickness and optic-disc size measurements by spectral-domain OCT

Background To evaluate the influence of axial length on measurements of the retinal nerve fibre layer (RNFL) thickness and optic nerve head (ONH) parameters in healthy subjects. Methods Using Cirrus HD-OCT, RNFL thickness and ONH parameters (disc and rim area) were measured in 15 short (<22.5 mm), 15 medium (22.51–25.5 mm) and 15 long (>25.51 mm) eyes. Results The mean axial length was 21.5±0.5 mm in short eyes, 24.1±0.8 mm in medium eyes and 26.6±1.0 mm in long eyes. The RNFL thickness decreased with longer axial lengths in the superior (r=−0.52, r2=0.27, p=0.0003), inferior (r=−0.72, r2=0.52, p<0.0001), nasal (r=−0.60, r2=0.37, p<0.0001) and temporal (r=−0.30, r2=0.09, p=0.0485) quadrants, as well as in the 360° mean measurement (r=−0.69, r2=0.48, p<0.0001). The optic-disc area (r=−0.74, r2=0.54, p<0.0001) and rim area (r=−0.41, r2=0.17, p=0.0051) decreased with longer axial lengths. Correcting for axial length-induced ocular magnification by means of the Littmann formula resolved the relationship between axial length and both RNFL thickness and ONH area. Discussion Axial length influences measurements of RNFL thickness and ONH parameters in healthy subjects. Caution is recommended when comparing the measured values of myopic and hyperopic eyes with the normative database of the instrument.

Repeatability of automatic measurements by a new Scheimpflug camera combined with Placido topography

PURPOSE: To assess the repeatability of anterior segment measurements performed by a Scheimpflug camera combined with Placido corneal topography (Sirius) in unoperated, post‐refractive surgery, and keratoconus eyes. SETTING: Private clinical ophthalmology practice. DESIGN: Evaluation of diagnostic test or technology. METHODS: Three consecutive scans were acquired for each eye. The following parameters were evaluated: simulated keratometry, posterior corneal power, mean pupil power (ie, corneal power assessed by ray tracing through the anterior and posterior corneal surfaces), corneal asphericity, thinnest and apex corneal thickness, aqueous depth, anterior chamber volume, and corneal spherical aberration. Repeatability was assessed using test–retest variability, the coefficient of variation, and the intraclass correlation coefficient (ICC). RESULTS: Sixty‐four unoperated eyes, 17 eyes that had myopic excimer laser surgery, and 13 eyes with keratoconus were analyzed. High repeatability was achieved for most parameters in the 3 groups, with an ICC higher than 0.99 for all measurements except posterior corneal power and mean pupil power in keratoconus (ICC, 0.868 and 0.976, respectively), anterior and posterior asphericity in normal eyes (ICC, 0.904 and 0.977, respectively), and spherical aberration in normal eyes (ICC, 0.806), post‐refractive surgery eyes (ICC, 0.980), and keratoconus eyes (ICC, 0.981). CONCLUSION: The anterior segment measurements provided by the new Scheimpflug camera–Placido corneal topography system were highly repeatable and can be relied on in clinical routine and for research purposes. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Visual system involvement in patients with Friedreich's ataxia

Optic neuropathy is common in mitochondrial disorders, but poorly characterized in Friedreichs ataxia (FRDA), a recessive condition caused by lack of the mitochondrial protein frataxin. We investigated 26 molecularly confirmed FRDA patients by studying both anterior and posterior sections of the visual pathway using a new, integrated approach. This included visual field testing and optical coherence tomography (OCT), pattern visual evoked potentials (P-VEPs) and diffusion-weighted imaging. The latter was used to study optic radiation by calculating water apparent diffusion coefficients (ADC). All patients suffered optic nerve involvement with their disorder. Different patterns of visual field defects were observed and a variably reduced retinal nerve fiber layer thickness was seen by OCT in all cases. P-VEPs were abnormal in approximately half of the patients. Decreased visual acuity and temporal optic disc pallor were present in advanced stages of the disease, but only five patients were symptomatic. Two of these patients suffered a sudden loss of central vision, mimicking Lebers hereditary optic neuropathy (LHON), and of the other three symptomatic patients two were noted to be compound heterozygotes. ADC values of optic radiations in patients were significantly higher than controls (P < 0.01). Retinal nerve fiber layer thickness at OCT and P-VEPs correlated with age at onset and ICARS total score. ADC values correlated with age at onset, disease duration, GAA triplet expansion size, ICARS total score and P-VEPs. Visual pathway involvement is found consistently in FRDA, being previously underestimated, and we here document that it also involves the optic radiations. Occasional LHON-like cases may occur. However, optic neuropathy in FRDA substantially differs from classic mitochondrial optic neuropathies implying a different pathophysiology of visual system degeneration in this mitochondrial disease.

Comparison of 2 laser instruments for measuring axial length.

PURPOSE: To compare axial length (AL), anterior chamber depth (ACD), and keratometric (K) measurements of 2 laser biometers. SETTING: Private practices, Lynwood and Santa Monica, California, USA. METHODS: In this prospective comparative observational study of eyes with cataract and eyes with a clear lens, AL, ACD, and K measurements were performed using an IOLMaster biometer, which uses partial coherence interferometry (PCI), and a Lenstar LS 900 biometer, which uses optical low‐coherence reflectometry (OLCR). Intraocular lens (IOL) power calculation was performed using the Haigis formula. The IOL prediction error was calculated for each eye. RESULTS: The study evaluated 50 eyes with cataract and 50 eyes with a clear lens. There was a good correlation between AL, ACD, and K measurements in the cataractous eyes (r = 0.9993, 0.9667, and 0.9959, respectively) and in eyes with a clear lens (r = 0.9995, 0.8211, and 0.9959, respectively). The OLCR unit measured a slightly longer AL in the cataract group and clear lens group (mean difference 0.026 mm and 0.023 mm, respectively), a deeper ACD (0.128 mm and 0.146 mm, respectively), and a flatter K (−0.107 diopter [D] and −0.121 D, respectively). The differences were statistically significant (P<.0001). The mean absolute error in IOL power prediction was 0.455 D ± 0.32 (SD) with the OLCR unit and 0.461 ± 0.31 D with the PCI unit (P>.1). CONCLUSIONS: Measurements were comparable between the OLCR device and the PCI device. A slight decrease (0.050) in the a0 constant is recommended if the Haigis formula is used. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Repeatability of automatic measurements performed by a dual Scheimpflug analyzer in unoperated and post-refractive surgery eyes

PURPOSE: To assess the repeatability of the anterior segment measurements performed with a dual Scheimpflug analyzer (Galilei) in unoperated and post‐refractive surgery eyes. SETTING: Private practice. DESIGN: Evaluation of diagnostic test. METHODS: Three consecutive scans were acquired in unoperated eyes and in eyes that had excimer laser surgery for myopia. Unoperated eyes were enrolled from 3 subgroups: younger than 50 years, aged between 50 and 70 years, and older than 70 years. The following parameters were evaluated: simulated keratometry, posterior corneal power, total corneal power, anterior and posterior best‐fit sphere radius, mean and thinnest central corneal thickness, anterior chamber depth and volume, horizontal and vertical corneal diameter, iridocorneal angle in the 4 quadrants, and corneal spherical aberration. Repeatability was assessed using analysis of variance (ANOVA), the coefficient of variation (COV), intraclass correlation (ICC), and test–retest variability. RESULTS: The study evaluated 45 unoperated eyes (n = 45) and 15 post‐refractive surgery eyes (n = 15). Each age subgroup in the unoperated group comprised 15 eyes. The ANOVA did not detect significant differences between the 3 measurements for any parameter. The COV was less than 0.5% for corneal power measurements and less than 3.5% for all remaining parameters except spherical aberration (16.68%). The ICC was more than 0.99 for corneal power measurements and more than 0.94 for all remaining parameters. CONCLUSIONS: The anterior segment measurements provided by the dual Scheimpflug analyzer were highly repeatable. Repeatability did not change with age or after myopic photorefractive keratectomy or laser in situ keratomileusis. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Influence of pupil size and cataract on retinal nerve fiber layer thickness measurements by Stratus OCT.

AimTo investigate whether retinal nerve fiber layer (RNFL) thickness, as measured by optical coherence tomography (OCT), is influenced by pupil size and cataract. MethodsRNFL thickness was measured by means of Stratus OCT (RNFL Thickness 3.4 acquisition protocol) in a group of consecutive patients undergoing phacoemulsification and intraocular lens implantation. Measurements were taken preoperatively without pupil dilation (PR1), preoperatively with pupil dilation (PR2), and 1 month postoperatively without pupil dilation. ResultsTwenty-five eyes of 25 patients were enrolled in the study and underwent statistical analysis. Pupil dilation caused RNFL thickness measurements to increase slightly in PR2 compared with PR1; the difference showed to be statistically significant in the 360-degree average measurement (P=0.0456) and in the nasal quadrant (P=0.032), but not in the remaining quadrants. Postoperative measurements were higher than those of PR1 in all quadrants (temporal P=0.011; superior P=0.0098; nasal P<0.0001; inferior P=0.0081) and in 360 degrees average (P<0.0001), suggesting that the presence of cataract significantly influences RNFL thickness as measured by Stratus OCT. More advanced degrees of lens opacity were correlated to a higher decrease in RNFL thickness values (r=0.4071, P=0.0434). ConclusionsWhile pupil size only marginally affects RNFL measurements performed by Stratus OCT, the presence and degree of cataract seem to have a significant impact. This effect should be taken in consideration when using this technology for the diagnosis of glaucoma and other neuro-ophthalmologic disorders possibly affecting the RNFL.

Use of a Support Vector Machine for Keratoconus and Subclinical Keratoconus Detection by Topographic and Tomographic Data

PURPOSE To define a new classification method for the diagnosis of keratoconus based on corneal measurements provided by a Scheimpflug camera combined with Placido corneal topography (Sirius, CSO, Florence, Italy). DESIGN Retrospective case series. PARTICIPANTS We analyzed the examinations of 877 eyes with keratoconus, 426 eyes with subclinical keratoconus, 940 eyes with a history of corneal surgery (defined as abnormal), and 1259 healthy control eyes. METHODS For each group, eyes were divided into a training and a validation set. A support vector machine (SVM) was used to analyze the corneal measurements and classify the eyes into the 4 groups of participants. The classifier was trained to consider the indices obtained from both the anterior and posterior corneal surfaces or only from the anterior corneal surface. MAIN OUTCOME MEASURES Symmetry index of front and back corneal curvature, best fit radius of the front corneal surface, Baiocchi Calossi Versaci front index (BCV(f)) and BCV back index (BCV(b)), root mean square of front and back corneal surface higher order aberrations, and thinnest corneal point were analyzed. The diagnostic performance of the classifier was evaluated. RESULTS The accuracy of the classifier was excellent both with and without the data generated from the posterior corneal surface and corneal thickness because the number of true predictions was greater than 95% and 93%, respectively, in all classes. Precision improved most when posterior corneal surface data were included, especially in cases of subclinical keratoconus. Using the data from both anterior and posterior corneal surfaces and pachymetry allowed the SVM to increase its sensitivity from 89.3% to 96.0% in abnormal eyes, 92.8% to 95.0% in eyes with keratoconus, 75.2% to 92.0% in eyes with subclinical keratoconus, and 93.1% to 97.2% in normal eyes. CONCLUSIONS The classification algorithm showed high accuracy, precision, sensitivity, and specificity in discriminating among abnormal eyes, eyes with keratoconus or subclinical keratoconus, and normal eyes. Including the posterior corneal surface and thickness parameters markedly improved the sensitivity in the diagnosis of subclinical keratoconus. Classification may be particularly useful in excluding eyes with early signs of corneal ectasia when screening patients for excimer laser surgery.