AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype-Phenotype Characterization Compared to OPA1 Patients.

PURPOSE: Heterozygous mutations in the AFG3L2 gene (encoding a mitochondrial protease indirectly reflecting on OPA1 cleavage) and ACO2 gene (encoding the mitochondrial enzyme aconitase) are associated with isolated forms of Dominant Optic Atrophy (DOA). We aimed at describing their neuro-ophthalmological phenotype as compared with classic OPA1-related DOA. DESIGN: Cross-sectional study. METHODS: The following neuro-ophthalmological parameters were collected: logMAR visual acuity (VA), color vision, mean deviation and foveal threshold at visual fields, average and sectorial retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thickness on optical coherence tomography. ACO2 and AFG3L2 patients were compared with an age- and sex-matched group of OPA1 patients with a 1:2 ratio. All eyes were analyzed using a clustered Wilcoxon rank sum test with the Rosner-Glynn-Lee method. RESULTS: A total of 44 eyes from 23 ACO2 patients and 26 eyes from 13 AFG3L2 patients were compared with 143 eyes from 72 OPA1 patients. All cases presented with bilateral temporal-predominant optic atrophy with various degree of visual impairment. Comparison between AFG3L2 and OPA1 failed to reveal any significant difference. ACO2 patients compared to both AFG3L2 and OPA1 presented overall higher values of nasal RNFL thickness (P = .029, P = .023), average thickness (P = .012, P = .0007), and sectorial GCL thickness. These results were confirmed also comparing separately affected and subclinical patients. CONCLUSIONS: Clinically, DOA remains a fairly homogeneous entity despite the growing genetic heterogeneity. ACO2 seems to be associated with an overall better preservation of retinal ganglion cells, probably depending on the different pathogenic mechanism involving mtDNA maintenance, as opposed to AFG3L2, which is involved in OPA1 processing and is virtually indistinguishable from classic OPA1-DOA.

Chromatic Pupillometry in Isolated Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Melanopsin retinal ganglion cell (mRGC)-mediated pupillary light reflex (PLR) abnormalities have been documented in several neurodegenerative disorders including Parkinson's disease. Overall, isolated rapid eye movement (REM) sleep behavior disorder (iRBD) represents the strongest prodromal risk factor for impending α-synucleinopathies. OBJECTIVES: To quantitatively compare PLR and mRGC-mediated contribution to PLR in 16 iRBD patients and 16 healthy controls. METHODS: iRBD and controls underwent extensive neuro-ophthalmological evaluation and chromatic pupillometry. In iRBD, PLR metrics were correlated with clinical variables and with additional biomarkers including REM atonia index (RAI), DaTscan, and presence of phosphorylated-α-synuclein (p-α-syn) deposition in skin biopsy. RESULTS: We documented higher baseline pupil diameter and decreased rod-transient PLR amplitude in iRBD patients compared to controls. PLR rod-contribution correlated with RAI. Moreover, only iRBD patients with evidence of p-α-syn deposition at skin biopsy showed reduced PLR amplitude compared to controls. CONCLUSION: The observed PLR abnormalities in iRBD might be considered as potential biomarkers for the risk stratification of phenoconversion of the disease. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dominant ACO2 mutations are a frequent cause of isolated optic atrophy.

Biallelic mutations in ACO2, encoding the mitochondrial aconitase 2, have been identified in individuals with neurodegenerative syndromes, including infantile cerebellar retinal degeneration and recessive optic neuropathies (locus OPA9). By screening European cohorts of individuals with genetically unsolved inherited optic neuropathies, we identified 61 cases harbouring variants in ACO2, among whom 50 carried dominant mutations, emphasizing for the first time the important contribution of ACO2 monoallelic pathogenic variants to dominant optic atrophy. Analysis of the ophthalmological and clinical data revealed that recessive cases are affected more severely than dominant cases, while not significantly earlier. In addition, 27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy. In silico analyses of ACO2 variants predicted their deleterious impacts on ACO2 biophysical properties. Skin derived fibroblasts from patients harbouring dominant and recessive ACO2 mutations revealed a reduction of ACO2 abundance and enzymatic activity, and the impairment of the mitochondrial respiration using citrate and pyruvate as substrates, while the addition of other Krebs cycle intermediates restored a normal respiration, suggesting a possible short-cut adaptation of the tricarboxylic citric acid cycle. Analysis of the mitochondrial genome abundance disclosed a significant reduction of the mitochondrial DNA amount in all ACO2 fibroblasts. Overall, our data position ACO2 as the third most frequently mutated gene in autosomal inherited optic neuropathies, after OPA1 and WFS1, and emphasize the crucial involvement of the first steps of the Krebs cycle in the maintenance and survival of retinal ganglion cells.

ATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy.

OBJECTIVE: Dominant optic atrophy (DOA) is the most common inherited optic neuropathy, with a prevalence of 1:12,000 to 1:25,000. OPA1 mutations are found in 70% of DOA patients, with a significant number remaining undiagnosed. METHODS: We screened 286 index cases presenting optic atrophy, negative for OPA1 mutations, by targeted next generation sequencing or whole exome sequencing. Pathogenicity and molecular mechanisms of the identified variants were studied in yeast and patient-derived fibroblasts. RESULTS: Twelve cases (4%) were found to carry novel variants in AFG3L2, a gene that has been associated with autosomal dominant spinocerebellar ataxia 28 (SCA28). Half of cases were familial with a dominant inheritance, whereas the others were sporadic, including de novo mutations. Biallelic mutations were found in 3 probands with severe syndromic optic neuropathy, acting as recessive or phenotype-modifier variants. All the DOA-associated AFG3L2 mutations were clustered in the ATPase domain, whereas SCA28-associated mutations mostly affect the proteolytic domain. The pathogenic role of DOA-associated AFG3L2 mutations was confirmed in yeast, unraveling a mechanism distinct from that of SCA28-associated AFG3L2 mutations. Patients' fibroblasts showed abnormal OPA1 processing, with accumulation of the fission-inducing short forms leading to mitochondrial network fragmentation, not observed in SCA28 patients' cells. INTERPRETATION: This study demonstrates that mutations in AFG3L2 are a relevant cause of optic neuropathy, broadening the spectrum of clinical manifestations and genetic mechanisms associated with AFG3L2 mutations, and underscores the pivotal role of OPA1 and its processing in the pathogenesis of DOA. ANN NEUROL 2020 ANN NEUROL 2020;88:18-32.

International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy.

Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000-45,000). Its molecular pathogenesis and natural history is now fairly well understood. LHON also is the first mitochondrial disease for which a treatment has been approved (idebenone-Raxone, Santhera Pharmaceuticals) by the European Medicine Agency, under exceptional circumstances because of the rarity and severity of the disease. However, what remains unclear includes the optimal target population, timing, dose, and frequency of administration of idebenone in LHON due to lack of accepted definitions, criteria, and general guidelines for the clinical management of LHON. To address these issues, a consensus conference with a panel of experts from Europe and North America was held in Milan, Italy, in 2016. The intent was to provide expert consensus statements for the clinical and therapeutic management of LHON based on the currently available evidence. We report the conclusions of this conference, providing the guidelines for clinical and therapeutic management of LHON.

Intraocular lens power calculation after myopic excimer laser surgery: Selecting the best method using available clinical data.

PURPOSE: To compare the results of methods to calculate intraocular lens (IOL) power after myopic excimer laser surgery. SETTING: G.B. Bietti Foundation-IRCCS, Rome, Italy. DESIGN: Prospective interventional case series. METHODS: Eyes were classified into 4 groups: Group 1 (preoperative keratometry available, refractive change known), Group 2 (preoperative keratometry available, refractive change uncertain), Group 3 (preoperative keratometry unavailable, refractive change known), and Group 4 (preoperative keratometry unavailable, refractive change unknown). The IOL power was calculated by 19 methods. The median absolute error in refraction prediction and the percentage of eyes with a refraction prediction error within ±0.50 diopter (D) were calculated. RESULTS: In Group 1 (n = 30), the Savini, Seitz/Speicher/Savini, and Masket methods provided the lowest median absolute error (0.29 D, 0.35 D, and 0.34 D, respectively), with more than 70% of eyes within ±0.50 D of the predicted refraction. In Group 2 (n = 16), the Seitz/Speicher method achieved the best result (median absolute error 0.37 D), with 75% of eyes within ±0.50 D of the predicted refraction. In Group 3 (n = 18), the Masket method provided the lowest median absolute error (0.24 D), with 72.2% of eyes within ±0.50 D of the predicted refraction. In Group 4 (n = 6), the Shammas no-history method had the lowest median absolute error (0.31 D), with 83% of eyes within ±0.50 D of the predicted refraction. CONCLUSION: Intraocular lens power can be accurately calculated in post-laser surgery eyes when the preoperative corneal power and refractive change are known and when they are not. FINANCIAL DISCLOSURE: Dr. Hoffer receives book royalties for IOL Power and formula royalties from all manufacturers using the Hoffer Q formula to ensure it is programmed correctly. No other author has a financial or proprietary interest in any material or method mentioned.

Macular Microcysts in Mitochondrial Optic Neuropathies: Prevalence and Retinal Layer Thickness Measurements.

PURPOSE: To investigate the thickness of the retinal layers and to assess the prevalence of macular microcysts (MM) in the inner nuclear layer (INL) of patients with mitochondrial optic neuropathies (MON). METHODS: All patients with molecularly confirmed MON, i.e. Leber's Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), referred between 2010 and 2012 were enrolled. Eight patients with MM were compared with two control groups: MON patients without MM matched by age, peripapillary retinal nerve fiber layer (RNFL) thickness, and visual acuity, as well as age-matched controls. Retinal segmentation was performed using specific Optical coherence tomography (OCT) software (Carl Zeiss Meditec). Macular segmentation thickness values of the three groups were compared by one-way analysis of variance with Bonferroni post hoc corrections. RESULTS: MM were identified in 5/90 (5.6%) patients with LHON and 3/58 (5.2%) with DOA. The INL was thicker in patients with MON compared to controls regardless of the presence of MM [133.1±7µm vs 122.3±9µm in MM patients (p<0.01) and 128.5±8µm vs. 122.3±9µm in no-MM patients (p<0.05)], however the outer nuclear layer (ONL) was thicker in patients with MM (101.4±1mµ) compared to patients without MM [77.5±8mµ (p<0.001)] and controls [78.4±7mµ (p<0.001)]. ONL thickness did not significantly differ between patients without MM and controls. CONCLUSION: The prevalence of MM in MON is low (5-6%), but associated with ONL thickening. We speculate that in MON patients with MM, vitreo-retinal traction contributes to the thickening of ONL as well as to the production of cystic spaces.

Syndromic parkinsonism and dementia associated with OPA1 missense mutations.

OBJECTIVE: Mounting evidence links neurodegenerative disorders such as Parkinson disease and Alzheimer disease with mitochondrial dysfunction, and recent emphasis has focused on mitochondrial dynamics and quality control. Mitochondrial dynamics and mtDNA maintenance is another link recently emerged, implicating mutations in the mitochondrial fusion genes OPA1 and MFN2 in the pathogenesis of multisystem syndromes characterized by neurodegeneration and accumulation of mtDNA multiple deletions in postmitotic tissues. Here, we report 2 Italian families affected by dominant chronic progressive external ophthalmoplegia (CPEO) complicated by parkinsonism and dementia. METHODS: Patients were extensively studied by optical coherence tomography (OCT) to assess retinal nerve fibers, and underwent muscle and brain magnetic resonance spectroscopy (MRS), and muscle biopsy and fibroblasts were analyzed. Candidate genes were sequenced, and mtDNA was analyzed for rearrangements. RESULTS: Affected individuals displayed a slowly progressive syndrome characterized by CPEO, mitochondrial myopathy, sensorineural deafness, peripheral neuropathy, parkinsonism, and/or cognitive impairment, in most cases without visual complains, but with subclinical loss of retinal nerve fibers at OCT. Muscle biopsies showed cytochrome c oxidase-negative fibers and mtDNA multiple deletions, and MRS displayed defective oxidative metabolism in muscle and brain. We found 2 heterozygous OPA1 missense mutations affecting highly conserved amino acid positions (p.G488R, p.A495V) in the guanosine triphosphatase domain, each segregating with affected individuals. Fibroblast studies showed a reduced amount of OPA1 protein with normal mRNA expression, fragmented mitochondria, impaired bioenergetics, increased autophagy and mitophagy. INTERPRETATION: The association of CPEO and parkinsonism/dementia with subclinical optic neuropathy widens the phenotypic spectrum of OPA1 mutations, highlighting the association of defective mitochondrial dynamics, mtDNA multiple deletions, and altered mitophagy with parkinsonism.

Scheimpflug analysis of corneal power changes after myopic excimer laser surgery.

PURPOSE: To assess the ability of corneal power measurements by a rotating Scheimpflug camera to measure the refractive change induced by myopic excimer laser surgery. SETTING: G.B. Bietti Foundation-IRCCS, Rome, Italy. DESIGN: Evaluation of diagnostic test. METHODS: The following corneal power measurements by the Pentacam Scheimpflug camera were analyzed: average keratometry (K), true net power (calculated by Gaussian optics formula), and total corneal refractive power (TCRP) at 2.0 mm, 3.0 mm, and 4.0 mm, calculated by ray tracing on a ring and as the average of the zone inside the ring. The difference between the preoperative and postoperative values was compared with the subjective surgically induced refractive change (SIRC) and with the difference between the preoperative and the postoperative anterior corneal power measured by Placido corneal topography (Keratron). RESULTS: In 36 consecutive eyes, the average K significantly underestimated the SIRC as determined by subjective refraction (-4.47 diopters [D] ± 1.81 [SD]) and corneal topography (-4.38 ± 1.81 D). The 3.0 mm and 4.0 mm ring total corneal refractive power significantly overestimated the SIRC. The remaining values did not show statistically significant differences with respect to the SIRC. The 3.0 mm zone TCRP and the 2.0 mm ring TCRP provided the lowest median difference compared with the SIRC (-0.07 D and -0.17 D, respectively) and the closest agreement. CONCLUSIONS: The corneal power values provided by the Scheimpflug camera accurately reflected the SIRC after myopic excimer laser surgery. The best options seem to be the 3.0 mm zone TCRP and the 2.0 mm ring TCRP.

Comparison of methods to measure corneal power for intraocular lens power calculation using a rotating Scheimpflug camera.

PURPOSE: To assess the accuracy of corneal power measurements provided by a Scheimpflug camera (Pentacam HR) for intraocular lens (IOL) power calculation in unoperated eyes and compare the results with those of simulated keratometry (SimK) performed with a Placido-disk corneal topographer (Keratron). SETTING: Private practice. DESIGN: Evaluation of diagnostic test. METHODS: Eight Scheimpflug camera corneal power measurements were analyzed: (1) average K, (2) true net power calculated using the Gaussian optics formula, (3) total corneal refractive power at 2.0 mm calculated by ray tracing on a ring and (4) as the average of the zone inside the ring, (5) total corneal refractive power at 3.0 mm on a ring and (6) as the average of the zone inside the ring, (7) the equivalent K reading at 3.0 mm and (8) at 4.5 mm. The IOL power was calculated using the Hoffer Q, Holladay 1, and SRK/T formulas. RESULTS: No statistically significant differences were observed between any corneal power measurements, including simulated K, in 41 consecutive patients. The latter showed slightly lower mean absolute errors with all 3 formulas (range 0.26 to 0.27 diopter [D]). The Scheimpflug camera gave the lowest median absolute errors with all formulas; that is, the 3.0 mm equivalent K reading with the Hoffer Q formula (0.18 D) and Holladay 1 formula (0.17 D) and the 2.0 mm total corneal refractive power ring with the SRK/T formula (0.18 D). CONCLUSION: Corneal power measurements provided by the Scheimpflug camera and Placido disk corneal topographer displayed comparable accuracy in IOL power calculation.

Anterior chamber and aqueous depth measurement in pseudophakic eyes: agreement between ultrasound biometry and scheimpflug imaging.

PURPOSE: To compare anterior chamber depth (ACD) and aqueous depth (AQD) measurements provided by a Scheimpflug camera combined with corneal topography to those obtained by immersion ultrasound (US) biometry when assessing the distance between the cornea and intraocular lens (IOL) in pseudophakic patients. METHODS: In a sample of 40 consecutive patients, each patient underwent measurements of ACD and AQD by means of the two techniques. Scheimpflug (Sirius; C.S.O., Firenze, Italy) measurements were obtained by manually tracing a line between the anterior surface of the IOL and the central cornea. Results were compared by t test. Agreement was evaluated by Bland-Altman plots with 95% limits of agreement (LoA). RESULTS: There was no statistically significant difference between the AQD as measured by US (3.95 ± 0.34 mm; range: 3.39 to 4.74 mm) and the AQD as measured by Scheimpflug photography (3.96 ± 0.34 mm; range: 3.41 to 4.77 mm; P = .3187). The statistically (but not clinically) significant difference between the ACD as measured by US (4.54 ± 0.37 mm; range: 3.93 to 5.35 mm) and Scheimpflug photography (4.58 ± 0.34 mm; range: 4.03 to 5.36 mm; P = .0024) disappeared after setting the US speed for ACD at 1,545 m/sec (mean ACD: 4.58 ± 0.37 mm; range: 3.96 to 5.39 mm). The 95% LoA ranged between -0.15 and +0.18 mm for AQD and between -0.12 and +0.21 mm for ACD. CONCLUSIONS: In pseudophakic eyes, the manual ACD and AQD measurements obtained from the Scheimpflug camera combined with corneal topography are not significantly different compared to those provided by US and therefore can be considered interchangeable with the latter.

Influence of axial length and corneal power on the astigmatic power of toric intraocular lenses.

PURPOSE: To assess the influence of the anterior chamber depth (ACD), predicted by corneal power (keratometry [K]), and axial length (AL) on the astigmatic power of toric intraocular lenses (IOLs). SETTING: Private practice, Bologna, Italy. DESIGN: Noninterventional theoretical study. METHODS: Meridional analysis (based on the Hoffer Q formula) was applied to an eye model with K ranging from 38.0 to 48.0 diopters and AL ranging from 20 to 30 mm. For each diopter (D) of K and each millimeter of AL, the ratio between the toricity at the IOL plane and the toricity at the corneal plane was computed. Several simulations with the Acrysof toric IOL were performed. RESULTS: The ratio between toricity at the IOL plane and toricity at the corneal plane depended on the predicted ACD. The highest value (1.86) was found with the steepest K (48.0 D) and longest AL (30.0 mm) and the lowest value (1.29), with the flattest K (38.0 D) and shortest AL (20.0 mm). When applied to the toric IOL, the results suggest that a low ratio (≤1.41) led to overcorrection of astigmatism relative to the value reported by the manufacturer's online calculator. In contrast, a high ratio (>1.60) led to undercorrection of the astigmatism. CONCLUSION: The ACD influenced the ratio between the cylinder power in the IOL plane and the cylinder power in the corneal plane and should be accounted for when selecting a toric IOL in an eye whose K and AL are far from the average values.

Accuracy of corneal power measurements by a new Scheimpflug camera combined with Placido-disk corneal topography for intraocular lens power calculation in unoperated eyes.

PURPOSE: To assess the accuracy of the corneal power measurements with a new Scheimpflug camera combined with Placido-disk corneal topography (Sirius) (combined Scheimpflug camera-topographer) for intraocular lens (IOL) power calculation in unoperated eyes and compare the results with those by a validated corneal topographer (Keratron) (validated topographer). SETTING: Private practice. DESIGN: Case series. METHODS: Consecutive patients having phacoemulsification and in-the-bag IOL implantation were studied. Intraocular lens power was calculated using the Hoffer Q, Holladay 1, and SRK/T formulas; the axial length, as measured by ultrasound immersion biometry; and 3 corneal power measurements: validated topographer simulated keratometry (K); combined Scheimpflug camera-topographer simulated K (derived from anterior corneal curvature only); combined Scheimpflug camera-topographer mean pupil power (derived from anterior and posterior corneal curvatures through ray tracing). The prediction error was calculated as the difference between the predicted refraction and the refraction measured 1 month postoperatively. RESULTS: When the corneal power measurements from the combined Scheimpflug camera-topographer were used, the mean absolute error (MAE) ranged between 0.23 diopter (D) ± 0.24 (SD) (simulated K and Hoffer Q formula) and 0.33 ± 0.23 D (mean pupil power and SRK/T formula). There were no statistically significant differences between the MAE generated by the simulated Ks of the 2 devices with any of the 3 formulas. CONCLUSION: Both corneal power measurements (simulated K and mean pupil power) provided by the new combined Scheimpflug camera-topographer were successfully entered into third-generation IOL power calculation formulas in unoperated eyes. FINANCIAL DISCLOSURE: Dr. Hoffer is the author of the Hoffer Q formula and owns the EyeLab, which sells Hoffer Programs. No other author has a financial or proprietary interest in any material or method mentioned.

Scheimpflug camera measurement of anterior and posterior corneal curvature in eyes with previous radial keratotomy.

PURPOSE: To compare the anterior and posterior corneal curvature in eyes with previous radial keratotomy (RK) to normal unoperated eyes. METHODS: In this retrospective observational case series, 29 eyes from 29 consecutive patients were analyzed and compared to a control group of 71 unoperated eyes. Corneal imaging was obtained by a rotating Scheimpflug camera (Pentacam, Oculus Optikgeräte GmbH). Anterior and posterior corneal curvature radii were measured at the 3-mm zone. RESULTS: The mean anterior and posterior corneal radii were 9.54 ± 0.89 and 8.54 ± 1.01 mm, respectively, both values being significantly higher than in the control group (7.81 ± 0.28 and 6.40 ± 0.24 mm, respectively, P<.0001). The mean anterior-to-posterior corneal curvature ratio was 1.12 ± 0.07, a value significantly lower than in the control group (1.22 ± 0.03, P<.0001). Mean corneal flattening was more evident in the posterior (33.44%) than in the anterior (22.15%) corneal curvature. The mean keratometric index, as calculated with the Gullstrand equation for thick lenses, was 1.3319 ± 0.0026, a value significantly higher than in the control group (1.3281 ± 0.0011, P<.0001). Linear regression detected a significant and directly proportional relationship between the number of radial incisions and flattening of both corneal surfaces (P<.0001). CONCLUSIONS: After RK, both corneal surfaces flatten but do not deform in parallel as commonly accepted, as shown by the fact that the anterior-to-posterior corneal curvature ratio decreases. This finding invalidates the standard keratometric index and thus has relevant implications for intraocular lens power calculation in RK eyes.

Comparison of anterior segment measurements by 3 Scheimpflug tomographers and 1 Placido corneal topographer.

PURPOSE: To compare the anterior segment measurements provided by 3 Scheimpflug tomographers and a Placido corneal topographer. SETTING: Private clinical ophthalmology practice. DESIGN: Evaluation of diagnostic test or technology. METHODS: In a sample of 25 consecutive patients having either refractive or cataract surgery, the anterior eye segment was analyzed by means of a rotating Scheimpflug camera (Pentacam), 2 devices with a Scheimpflug camera combined with a Placido disk (Sirius and TMS-5), and a Placido disk corneal topographer (Keratron). Measurement results were compared using analysis of variance. Agreement was assessed using Bland-Altman plots. RESULTS: The mean simulated keratometry (K) was different between the 4 instruments (P<.0001), with Keratron providing the highest value (44.43 diopters [D] ± 1.28 [SD]). The Pentacam and Sirius provided the lowest values (44.05 ± 1.21 D and 44.05 ± 1.27 D, respectively), without statistical difference (posttest). The mean posterior corneal power and minimum corneal thickness were statistically different between the 3 Scheimpflug cameras (P<.0001 and P=.0210, respectively); 95% limits of agreement, however, were narrow for posterior corneal power and large for corneal thickness. The only 2 devices measuring the distance between the corneal endothelium and the anterior lens surface showed a statistically but not clinically significant difference (2.90 ± 0.48 mm and 2.94 ± 0.47 mm, respectively). There were no statistically significant differences in anterior corneal asphericity between the 4 instruments. CONCLUSION: Although the measurements of some parameters by different instruments were similar, caution is warranted before using them interchangeably.

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.

Repeatability of optic nerve head parameters measured by spectral-domain OCT in healthy eyes.

BACKGROUND AND OBJECTIVE: To evaluate the repeatability of optic nerve head (ONH) measurements by spectral-domain optical coherence tomography. PATIENTS AND METHODS: Three scans were acquired in 32 healthy subjects during one session. Using Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA), the cup-to-disc ratio (CDR), disc area, rim area, cup volume, and horizontal and vertical CDRs were investigated. Repeatability was assessed by the coefficient of variation (COV), the test-retest intrasession variability, and the intraclass correlation coefficient (ICC). RESULTS: Good repeatability was achieved for all parameters, with a COV of 4.23% or less and ICCs of 0.98 or greater for all measurements. Test-retest intrasession variability was 0.024 for CDR, 0.121 mm(2) for disc area, 0.087 mm(2) for rim area, 0.017 mm(3) for cup volume, and 0.048 for horizontal and vertical CDR. CONCLUSION: In healthy eyes, Cirrus HD-OCT provides repeatable measurements of ONH parameters.

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.