Reduced Levels of Lacrimal Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Patients with Focal Epilepsy and Focal Epilepsy with Comorbid Depression: A Biomarker Candidate.

Our previous studies showed that in patients with brain diseases, neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in the control of neuronal networks in an epileptic brain, we aimed to assess the GDNF levels in LF and BS as well as the BDNF and the hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (FE) and epilepsy and comorbid depression (FE + MDD) and to compare them with those of patients with major depressive disorder (MDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in FE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. GDNF concentrations in LF and BS positively correlated in HC, but not in patient groups. BDNF level was lower in BS of patients compared with HC and higher in FE + MDD taking valproates. A reduction in the GDNF level in LF might be an important biomarker of FE. Logistic regression models demonstrated that the probability of FE can be evaluated using GDNF in LF and BDNF in BS; that of MDD using GDNF in LF and cortisol and TNF-α in BS; and that of epilepsy with MDD using GDNF in LF and TNF-α and BDNF in BS.

Glial cell line-derived neurotrophic factor (GDNF) in blood serum and lacrimal fluid of patients with a current depressive episode.

BACKGROUND: Many studies indicate a significant role of GDNF in the pathogenesis of the mood disorders, including bipolar disorder (BD) and major depressive disorder (MDD). Potentially, neurotrophic factors in lacrimal fluid (LF) could become biomarkers of various specific disorders. The aim of this study was to assess GDNF levels in LF and blood serum (BS) of patients with a current depressive episode (cDE). METHODS: We studied the glial cell line-derived neurotrophic factor (GDNF) concentration in the LF and BS of 39 healthy controls and 137 patients with a current depressive episode (cDE) (both subgroups members were 20-49 years): BD - 46 patients, MDD - 91 patients. RESULTS: GDNF concentration in BS of women with MDD was significantly lower than in men. In BD patients, univariate linear regression analysis revealed significant correlations between GDNF concentration in the LF and the use of anxiolytics or antidepressants. These correlations were confirmed by the multivariate linear regression analysis. A significant correlation between GDNF concentrations in the LF and BS was found in controls. LIMITATIONS: The unequal proportion of men in the BD group did not permit adjusting GDNF concentrations for sex. The collected LF was stimulated, which could influence GDNF levels. It should also be noted that the patients included in the study were not treatment- naïve. CONCLUSIONS: Our findings suggest that GDNF concentration in LF could be a biomarker of the cDE (both unipolar and bipolar), though the sensitivity of this potential biomarker may be lower in depressive patients with anxiety symptoms.

Glial cell line-derived neurotrophic factor (GDNF) in patients with primary open-angle glaucoma and age-related cataract.

Purpose: To study glial cell line-derived neurotrophic factor (GDNF) concentrations in aqueous humor (AH), lacrimal fluid (LF), and blood serum (BS) in patients with age-related cataract and primary open-angle glaucoma (POAG). Methods: GDNF was studied in AH, LF, and BS in 47 patients with age-related cataract, and 30 patients with POAG combined with cataract (one eye in each person). AH was sampled during cataract surgery. Results: GDNF concentration (pg/ml) in patients with POAG and cataract was lower than in cataract-only patients (p<0.001), both in AH (46.3±31.1 versus 88.9±46.9) and in LF (222±101 versus 344±134). The difference was not significant for the GDNF concentration in BS (194±56 versus 201±45). In the earlier (early and moderate) stages of POAG, compared to later (advanced and severe) stages, GDNF concentration was significantly lower in LF (176±99 versus 258±91; p = 0.027) and in BS (165±42 versus 217±55; p = 0.017), while GDNF concentration in AH showed an insignificant difference (40.0±25.7 versus 51.1±34.7). In patients with POAG, GDNF concentration in LF and BS was inversely correlated with the Humphrey visual field index: Pearson's correlation coefficient r = -0.465 (p = 0.01) for LF and r = -0.399 (p = 0.029) for BS. When compared to the cataract group, patients in the earlier stages of POAG showed significantly lower GDNF concentrations in all studied biologic fluids. Conclusions: Compared to patients with cataract only, GDNF levels are lower in the AH and LF of patients with POAG and cataract, especially at earlier stages of the disease (at these stages, the GDNF level in BS is also lower). At earlier stages of POAG, compared to later stages, GDNF content is lower in LF and BS. These data could serve as a reason for the therapeutic use of GDNF in patients with POAG.

Evaluation of Average Retinal Nerve Fiber Layer Measurement in Eyes with Refractive Errors.

SIGNIFICANCE: Optical coherence tomography (OCT) measurements of peripapillary retinal nerve fiber layer (pRNFL) play an important role in the diagnosis of glaucoma and optic atrophy. However, the interpretation of these measurements in patients with refractive errors, especially of a high degree, presents great difficulties. Optical coherence tomography instruments from most manufacturers do not take into account the effect of refractive errors, especially of a high degree, on quantitative measurements of pRNFL. PURPOSE: The aim of this study was to develop a simple and easy method for evaluation of average pRNFL in eyes with refractive errors. METHODS: Average pRNFL was measured by Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA) in 183 healthy White subjects (183 eyes) older than 40 years, with an axial length of the eye from 22.5 to 24.5 mm and spherical equivalent of refraction from -1.63 to 2.0 D. RESULTS: For an average pRNFL, normative database of eyes with refraction close to emmetropia was constructed. The calculated first and fifth percentiles for age groups 41 to 50, 51 to 60, 61 to 70, and 71 to 85 years were 81 and 83, 79 and 81, 78 and 80, and 76 and 79 µm, respectively. Littmann-Bennett formula was modified to calculate a table containing first and fifth percentiles for eyes with axial lengths of 19 to 30 mm in the same age groups. CONCLUSIONS: For the correct interpretation of the measurements of pRNFL in patients with refractive errors, an original table was proposed, which provides a quick assessment of the results obtained on the Cirrus HD-OCT device. The proposed new formulas make it easy to calculate a similar table for any optical coherence tomography device using existing databases or after collecting a normative database of eyes with refraction close to emmetropia.

Brain-derived neurotrophic factor in blood serum and lacrimal fluid of patients with focal epilepsy.

OBJECTIVE: To evaluate brain-derived neurotrophic factor (BDNF) level in blood serum (BS) and lacrimal fluid (LF) of people with epilepsy (PWE). METHODS: It was a case-control study of 72 consecutive patients with focal epilepsy (cases, Epilepsy group) and 60 age- and gender-matched healthy volunteers (controls). Based on comorbid depression, two subgroups of PWE were formed. BDNF level was measured by enzyme-linked immunosorbent assay (ELISA) in BS and LF. RESULTS: Compared to controls, BDNF level (pg/mL) in PWE was lower both in BS (22,520 ± 3810 vs. 26,360 ± 3090, P < 0.000) and in LF (100.8 ± 23.3 vs. 113.4 ± 19.3, P = 0.001). However, no significant correlation was found between BDNF level in BS and LF either in the Epilepsy group or in controls. No impact of comorbid depression on BDNF level was found either in BS or LF of PWE. We revealed a higher BDNF level in LF of men as compared to women in controls and a similar non-significant trend in PWE. Higher BDNF level in BS of PWE receiving valproates versus other AEDs was found, however, a relatively small number of observations and use of polytherapy in most cases should be taken into account. SIGNIFICANCE: In patients with focal epilepsy, BDNF level is decreased both in BS and LF, though with no correlation between them. No association of BDNF levels with age and epilepsy characteristics, as well as the occurrence of depression, was found. Low BDNF level in LF could be considered as a non-invasive biomarker of focal epilepsy.

Surgical treatment of macular holes with and without the use of autologous platelet-rich plasma.

PURPOSE: To compare the results of treatment of idiopathic full-thickness macular holes (MHs) with and without the use of autologous platelet-rich plasma (APRP). METHODS: This partially retrospective study included 152 patients (152 eyes) with MHs operated in the years 2010-2014 using conventional technology with internal limiting membrane peeling (control group) and 62 patients (62 eyes), operated by the same surgeons in 2015-2017 with additional application of APRP on MH (platelet group). Pre and postoperative best-corrected visual acuities (BCVA) were recorded, and retinal microstructure was studied using optical coherence tomography. Thirty-seven patients in the platelet group and 80 controls were followed for at least 12 months (for visual outcomes 15 controls were followed for 15-24 months). The data of 72 controls (72 eyes) were analyzed retrospectively. RESULTS: The minimum diameter of the MH in the platelet group was larger than in controls: 454 ± 186 vsersus 381 ± 148 µm (P = 0.003). Despite this, all MHs in the platelet group were closed, while in the control group 11 holes (7.2%) remained open (P = 0.036). The final mean BCVA, standardized by the minimum diameter of the macular hole, was higher in the platelet group by 3.9 ETDRS letters (P = 0.012). After surgery with APRP, foveal hyperreflective lesion (presumably glial proliferation) was found, which persisted in most large MHs, but gradually disappeared in small and most medium MHs. CONCLUSION: The use of APRP significantly improves the anatomical and functional results of treatment of idiopathic MHs. In very large MHs, APRP presumably enhances glial proliferation, which ensures their closure.

Genotype Phenotype Correlation and Variability in Microcephaly Associated With Chorioretinopathy or Familial Exudative Vitreoretinopathy.

Purpose: The purpose of this study was to analyze the natural history and phenotypic overlap of patients with microcephaly and a chorioretinopathy or familial exudative vitreoretinopathy (FEVR) ocular phenotype caused by mutations in KIF11, TUBGCP4, or TUBGCP6. Methods: Patients diagnosed with congenital microcephaly and chorioretinopathy or FEVR were included. Molecular investigations consisted of targeted genetic sequencing. Data from medical records, ophthalmologic examination and imaging, electroretinography, and visual fields were analyzed for systemic and ophthalmic features and evidence of posterior segment disease progression. Results: Twelve patients from 9 families were included and had a median of 8 years of follow-up. Nine patients had KIF11 variants, two had heterozygous TUBGCP6 variants, and one had heterozygous variants in TUBGCP4. All patients had reduced visual function and multiple individuals and families showed features of both chorioretinopathy and FEVR. Progression of posterior segment disease was highly variable, with some degree of increased atrophy of the macula or peripheral retina or increased vitreoretinal traction observed in 9 of 12 patients. Conclusions: Microcephaly due to mutations in KIF11, TUBGCP4, or TUBGCP6 can be associated with retinal disease on a spectrum from chorioretinal atrophy to FEVR-like posterior segment changes. Visually significant disease progression can occur and patients should be monitored closely by a team experienced in ophthalmic genetics.

Causes of ganglion cell-inner plexiform layer thinning in myopic eyes.

PURPOSE: The present study aimed to determine the main cause of ganglion cell-inner plexiform layer (GCIPL) thinning in long myopic eyes. METHODS: Optical coherence tomography was performed in 53 subjects with moderate or high myopia (53 eyes; myopia group) and 20 emmetropic subjects (20 eyes; control group). All subjects were over the age of 40 years. RESULTS: Compared groups did not differ in age, sex, and radius of corneal curvature. Spherical equivalent in the myopia group was - 8.2 ± 3.3 D (from - 4.0 to - 22.6 D). A specialized computer program was created to study the effect of the ocular magnification on the average GCIPL thickness. Based on the data of control subjects, a mathematical model was constructed, which showed a very little effect of ocular magnification on GCIPL thickness. It was confirmed by real measurements. After correction by the program, GCIPL thickness in myopes increased only slightly (from 73.9 ± 5.2 to 75.0 ± 5.2 µm, P < 0.000) remaining much lower than in controls (79.7 ± 6.3 µm, P < 0.000). Modeling myopic eye as an ellipsoid showed a significant increase in its surface area compared with emmetropia. Retinal stretching associated with an increase in the surface area of the eyeball explained most of the thinning of GCIPL in myopia. CONCLUSIONS: Ocular magnification is responsible for only a minor part of GCIPL thinning in myopia. Stretching of the retina in a long eye is the main cause of the GCIPL thinning. Myopic normative databases should be created to account for the GCIPL thinning in highly myopic eyes.

Brain-Derived Neurotrophic Factor in Patients with Primary Open-Angle Glaucoma and Age-related Cataract.

PURPOSE: To study brain-derived neurotrophic factor (BDNF) content in aqueous humor (AH), lacrimal fluid (LF), and blood serum (BS) in patients with age-related cataract and primary open-angle glaucoma (POAG). METHODS: BDNF was studied in 57 patients with age-related cataract, 55 patients with POAG combined with cataract, and 29 healthy controls (one eye in each person). AH was sampled during cataract surgery. RESULTS: The levels of BDNF in LF and BS did not differ in cataract patients and controls. The concentration of BDNF (pg/mL) in patients with POAG and cataract was lower than in cataract patients in AH (35.2 ± 14.2 vs. 54.6 ± 29.6, P < 0.001), LF (78.0 ± 25.1 vs. 116.2 ± 43.1, P < 0.001), and BS (19230 ± 5960 vs. 22440 ± 7580, P < 0.02), while the AH/LF ratio was similar (0.46 ± 0.18 vs. 0.48 ± 0.19). The AH level of BDNF declined in early POAG and relatively increased in the next stages of the disease, inversely correlating with visual field index (Pearson's correlation coefficient r = -0.404, P = 0.002) and average retinal nerve fiber layer thickness (r = -0.322, P = 0.018). BDNF contents in LF and BS were also the lowest in early POAG. BDNF in AH strongly correlated with its content in LF (r = 0.66, P < 0.000). A formula was suggested to calculate the AH concentration of BDNF basing on its content in LF. CONCLUSIONS: BDNF contents are decreased in AH, LF, and BS of patients with POAG demonstrating a significant decrease in the early POAG and relative increase in the next stages of the disease. A strong correlation exists between BDNF contents in AH and LF.

Ciliary neurotrophic factor in patients with primary open-angle glaucoma and age-related cataract.

Purpose: To study the ciliary neurotrophic factor (CNTF) concentration in the aqueous humor (AH), lacrimal fluid (LF), and blood serum (BS) in patients with age-related cataract and primary open-angle glaucoma (POAG). Methods: CNTF concentrations were studied in 61 patients with age-related cataract, 55 patients with POAG combined with cataract, and 29 healthy controls (one eye in each person). Preliminary experiments permitted us to extend the minimum quantifiable value of the CNTF Quantikine enzyme-linked immunosorbent assay (ELISA) kit to 2.5 pg/ml. Results: The levels of CNTF in LF and BS did not differ in patients with cataract and controls. The CNTF concentration (pg/ml) in patients with POAG and cataract was lower than in patients with cataract (p<0.001) in AH (39.9±26.2 versus 57.2±25.6) and in LF (25.7±14.9 versus 39.9±18.0). The differences were not statistically significant for the CNTF level in BS (5.45±4.72 versus 5.96±4.92) and the AH/LF ratio (1.69±1.05 versus 1.58±0.70). In the patients with POAG, the AH level of CNTF correlated with the visual field index (Pearson's correlation coefficient r = 0.35, p = 0.01). A statistically significant decrease in the AH and LF concentrations of CNTF was observed in patients in all stages of POAG compared with the cataract group. This decrease was particularly prominent in patients with severe glaucoma. Compared to patients with combined early and moderate stages of disease patients with advanced glaucoma showed an insignificant reduction in the median CNTF concentration in AH and LF. The serum CNTF concentration did not show any dependence on the glaucoma stage. The CNTF concentration in the AH strongly correlated with the CNTF concentration in the LF (r=0.71, p<0.000). A formula was suggested to calculate the concentration of CNTF in AH based on the CNTF concentration in LF. Conclusions: The CNTF concentration is reduced in the AH and LF of patients with POAG, especially in those with severe visual field loss. The CNTF concentration in AH and LF showed a strong correlation, and this phenomenon opens up new options for a noninvasive estimation of the CNTF concentration in AH. The CNTF concentration established in the AH, LF, and BS of patients with age-related cataract can serve as normative data for persons older than 50 years old.

Predicting anatomical results of surgical treatment of idiopathic macular hole.

AIM: To determine the parameters most informative in predicting the anatomical results of surgical treatment of idiopathic full-thickness macular hole (IMH). METHODS: One hundred and sixty-two consecutive patients (170 eyes) after primary operation for IMH were enrolled. Outcomes were classified as anatomical success when both IMH closure and restoration of the outer retinal structure were achieved. "Prospective" group included 108 patients (115 eyes) followed with optical coherence tomography (OCT) and microperimetry for 1y after surgery. Potential prognostic criteria, except microperimetry data, were tested in "retrospective" group (54 patients, 55 eyes). Prognostic value of each parameter was determined using receiver operating characteristic (ROC) analysis. Combined predictive power of the best prognostic parameters was tested with the use of linear discriminant analysis. RESULTS: IMH closure was achieved in 106 eyes (92%) in the prospective group and 49 eyes (89%) in the retrospective group. Despite anatomical closure, the outer retinal structure was not restored in two eyes in the first group and in one eye in the second group. Preoperative central subfield retinal thickness demonstrated the best discriminatory capability between eyes with anatomical success and failure: area under the ROC-curve (AUC) 0.938 (95% CI: 0.881-0.995), sensitivity 64% at fixed specificity 95% (cut-off value 300 µm) in the prospective group; sensitivity 57% and specificity 90% in the retrospective group. Other continuous parameters except tractional hole index (AUC: 0.796, 95% CI: 0.591-1.000) had significantly lower AUCs (P<0.05). The best combination of the parameters, established by discriminant analysis in the prospective group, could not confirm its predictive value in the retrospective group. CONCLUSION: Preoperative central subfield retinal thickness is a strong and probably the best predictor of anatomical results of IMH surgical treatment.

Posterior chamber phakic intraocular lens sizing based on iris pigment layer measurements by anterior segment optical coherence tomography.

PURPOSE: To use anterior segment optical coherence tomography (AS-OCT) to evaluate the clinical effectiveness of Implantable Collamer Lens posterior chamber phakic intraocular lens (PC pIOL) sizing based on measurement of the distance from the iris pigment end to the iris pigment end. SETTING: S. Fyodorov Eye Microsurgery Federal State Institution, Moscow, Russia. DESIGN: Evaluation of diagnostic test or technology. METHODS: Stage 1 was a prospective study. The sulcus-to-sulcus (STS) distance was measured using ultrasound biomicroscopy (UBM) (Vumax 2), and the distance from iris pigment end to iris pigment end was assessed using a proposed AS-OCT algorithm. Part 2 used retrospective data from patients after implantation of a PC pIOL with the size selected according to AS-OCT (Visante) measurements of the distance from iris pigment end to iris pigment end. The PC pIOL vault was measured by AS-OCT, and adverse events were assessed. RESULTS: Stage 1 comprised 32 eyes of 32 myopic patients (mean age 28.4 years ± 6.3 [SD]; mean spherical equivalent [SE] -13.11 ± 4.28 diopters [D]). Stage 2 comprised 29 eyes of 16 patients (mean age 27.7 ± 4.7 years; mean SE -16.55 ± 3.65 D). The mean STS distance (12.35 ± 0.47 mm) was similar to the mean distance from iris pigment end to iris pigment end distance (examiner 1: 12.36 ± 0.51 mm; examiner 2: 12.37 ± 0.53 mm). The PC pIOL sized using the new AS-OCT algorithm had a mean vault of 0.53 ± 0.18 mm and did not produce adverse events during the 12-month follow-up. In 16 of 29 eyes, the PC pIOL vault was within an optimum interval (0.35 to 0.70 mm). CONCLUSION: The new measurement algorithm can be effectively used for PC pIOL sizing. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Accommodative changes in anterior chamber depth in patients with high myopia.

PURPOSE: To study the accommodative changes in the central anterior chamber depth (ACD) in patients with high myopia using anterior segment optical coherence tomography (AS-OCT). SETTING: Cataract Surgery Department and Clinical & Functional Diagnostics Department, S. Fyodorov Eye Microsurgery Complex-Federal State Institution, Moscow, Russian Federation. DESIGN: Prospective case-control study. METHODS: The ACD measurements were obtained in the nonaccommodative state (baseline) and during accommodation using the Visante AS-OCT device. RESULTS: Thirty-six myopic eyes (36 patients; mean age 27 years; mean spherical equivalent (SE) -12.52 diopters [D]) and 31 emmetropic eyes (31 subjects; mean age 26 years; mean SE -0.39 D) were examined. At baseline, the mean ACD in both groups was similar. During accommodation, the mean maximum changes in the ACD were significantly less pronounced in the myopia group (-0.14 mm ± 0.07 [SD]; range -0.03 to -0.29 mm) than in the emmetropia group (-0.22 ± 0.08 mm; range -0.04 to -0.35 mm) (P<.0001). Ten patients in the myopia group had a critically shallow anterior chamber (ACD <2.8 mm) in the state of accommodation. CONCLUSIONS: Accommodative changes in the ACD were significantly less pronounced in eyes with high myopia than in emmetropic eyes. Still, the anterior chamber might become critically shallow during accommodation in some myopic eyes, and this should be taken into account when planning phakic intraocular lens implantation to correct high myopia. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Comparison of measurement error of Cirrus HD-OCT and Heidelberg Retina Tomograph 3 in patients with early glaucomatous visual field defect.

BACKGROUND: To compare the measurement error of Cirrus HD-OCT and Heidelberg Retina Tomograph 3 (HRT3) in patients with early glaucomatous visual field defect. METHODS: Thirty-nine consecutive patients (39 eyes) with early glaucomatous visual field defect were included. One eye of a patient was examined with Cirrus HD-OCT and HRT3 in one session. Each instrument was used by two operators, each taking two measurements in turn. We performed measurements of average retinal nerve fiber layer (RNFL) thickness and RNFL thickness in four quadrants with Cirrus HD-OCT and 13 stereometric parameters of the optic nerve head and RNFL with HRT3. RESULTS: Cirrus HD-OCT parameters performed much better than HRT3 stereometric parameters. Mean (for both operators) intraoperator within-subject coefficient of variation of the best Cirrus HD-OCT parameter (average RNFL thickness) was 2.6-2.7 times lower than the best HRT3 parameters [mean cup depth and rim area (P < 0.001)]. Mean intraoperator variability of RNFL thickness in quadrants (except nasal quadrant) was also significantly lower with OCT than with HRT. The interoperator within-subject coefficients of variation for both average RNFL thickness and RNFL thickness in all quadrants were significantly lower than the interoperator variability of best HRT3 parameter [mean cup depth (P < 0.001)]. The within-subject coefficient of variation of the average/mean RNFL thickness assessed by both instruments was 5.4-7.3 times lower for Cirrus HD-OCT. Among HRT3 parameters, mean cup depth, rim area and linear cup/disk ratio were the least variable, while cup volume, cup area and cup/disc area ratio were the most variable parameters. CONCLUSIONS: Cirrus HD-OCT provides excellent intrasession intra- and interoperator repeatability of the RNFL measurements, especially of the average RNFL thickness in primary open-angle glaucoma (POAG) patients and POAG suspects with early glaucomatous visual field defect. The measurement error (expressed as within-subject coefficient of variation) of RNFL measurements by Cirrus HD-OCT is much lower than the error of HRT3 measurements of stereometric parameters of the optic nerve head and RNFL.

Smoothness of ablation on polymethylmethacrylate plates with four scanning excimer lasers.

PURPOSE: To perform a quantitative evaluation of smoothness of ablation on polymethylmethacrylate (PMMA) using four scanning excimer lasers available commercially for photorefractive surgery. METHODS: Ablations were done on PMMA plates with dimensions 100 x 50 x 1 mm. Four scanning excimer lasers were used, two with flying spot technology (Zeiss-Meditec MEL-70, and a Russian-made unit, Microscan) and two Nidek models with scanning slit delivery systems and an expanding iris diaphragm (EC-5000 and EC-5000 CX). Forty PMMA plates were ablated with standard -3.00-D settings using an ablation zone of 6 mm; each laser ablated 10 plates. Measurements were made in the center of each plate with the Zygo microscope, based on the principle of white light interferometry. Smoothness of ablation was characterized by three surface parameters (RMS, Ra, PV). RMS was considered the most significant parameter. RESULTS: The smoothest surface was obtained in samples produced by Zeiss-Meditec MEL-70 unit (RMS=112 +/- 23 nm), followed by the Nidek EC-5000 CX (RMS=153 +/- 12 nm), and the Microscan (RMS=181 +/- 11 nm). The smoothness of ablation produced by the Nidek EC-5000 unit (RMS=329 +/- 39 nm) was significantly less than the other three lasers (P<.01). CONCLUSIONS: Scanning excimer lasers based on flying spot technology--Zeiss-Meditec MEL-70 and Microscan, as well as the Nidek EC-5000 CX with FlexScan--created smoother ablations on PMMA plates compared to the older Nidek EC-5000 unit.