Dynamic corneal biomechanics in different cell layers: in keratoconus and normal eyes.

PURPOSE: This study aimed to determine the relationship between corneal cellular structures and biomechanical deformation parameters in keratoconic (KC) and healthy eyes. METHODS: In this prospective comparative study, 29 eyes of 29 KC patients were age- and gender-matched with 28 eyes of 28 healthy individuals using frequency matching. Corneal parameters examined included the density of basal epithelial cells, anterior keratocytes, posterior keratocytes and endothelial cells as assessed by in vivo corneal confocal microscopy (HRT III-RCM, Heidelberg Engineering, www.heidelbergengineering.com). Additionally, the coefficient of variation of endothelial cell size (CV) and the percentage of hexagonal endothelial cells (HEX%) were measured by specular microscopy (Konan NSP-9900, Konan Medical, www.konanmedical.com). Further, biomechanical deformation parameters were derived from Corvis Scheimpflug Technology (Corvis ST, Oculus, www.oculus.de). All cellular and biomechanical deformation parameters in KC and normal groups were compared, and the relationship between cellular and biomechanical parameters calculated. RESULTS: In the KC group, the highest concavity (HC) delta arc length and maximum delta arc length were associated with endothelial cell density (Beta = -0.39, p = 0.03 and Beta = -0.60, p Ë‚ 0.001, respectively). Furthermore, there was a significant association between HC deflection length and HEX% (Beta = -0.67, p = 0.001). In the normal group, HC delta arc length and HC deflection length were significantly associated with endothelial cell density (Beta = 0.46, p = 0.02; and Beta = -0.51, p = 0.01, respectively). HC time, HC deformation amplitude and applanation 1 delta arc length were associated with CV (Beta = 0.50, p = 0.01; Beta = 0.27, p = 0.009; and Beta = -0.57, p = 0.002, respectively). Applanation 1 and applanation 2 deformation amplitudes were associated with HEX% (Beta = -0.49, p = 0.005; and Beta = -0.46, p = 0.02). CONCLUSIONS: Biomechanical deformation parameters were significantly correlated with endothelial cell properties in both KC and normal groups, thereby indicating the importance of the integrity of endothelial cells to the biomechanical properties of both KC and normal corneas.

Post-LASIK Ectasia Versus Keratoconus: An In Vivo Confocal Microscopy Study.

PURPOSE: To examine and compare corneal cellular and subbasal nerve (SBN) characteristics in post-laser-assisted in situ keratomileusis ectasia (PLE) corneas, normal post-laser-assisted in situ keratomileusis corneas (PLC), keratoconus (KC) corneas, and normal virgin corneas (NC). METHODS: In this cross-sectional comparative study, 18 PLE eyes of 11 patients, 18 PLC of 15 cases, 32 KC eyes of 32 patients, and 29 NC of 29 subjects were assessed using in vivo confocal microscopy. The density of the basal epithelial cell (BEC), anterior keratocyte, posterior keratocyte, and endothelial cell layers, as well as the characteristics of SBN fibers, was compared between the 4 groups. RESULTS: The density of the BEC and anterior and posterior keratocyte layers was significantly lower in KC compared with NC (-650 ± 190, P = 0.013; -181 ± 39, P < 0.001; and -36 ± 11, P = 0.021, respectively). However, there was no significant difference between PLE and PLC regarding these parameters (all Ps ≥ 0.6). Mean SBN parameters, including central corneal nerve branch density, nerve fiber length, total branch density, and nerve fiber area, were significantly lower in KC compared with NC and in PLE compared with PLC (all Ps ≤ 0.021). CONCLUSIONS: The pathophysiology of PLE seems to differ from KC. Apparent changes in the BEC and anterior and posterior keratocytes associated with KC were not observed in PLE. However, SBNs seem to be involved in both conditions.

Duration of topical steroid application after photorefractive keratectomy with mitomycin C.

Contradictory results of postoperative steroid application in photorefractive keratectomy (PRK) led to a meta-analysis of the existing data to achieve a definite conclusion on the optimum dosage and duration of corticosteroid therapy after PRK. The overall pooled unstandardized mean difference (PUMD) of the corneal haze score was -0.20 (95% CI, -0.29 to -0.12). In subgroup analysis, the PUMD of the corneal haze score was statistically significant in 2 subgroups, -0.57 (-0.85 to -0.30) for 3 to 6 months postoperatively and -0.13 (-0.23 to -0.04) for ≤ 3 months postoperatively. Analysis of the PUMD of postoperative spherical equivalent in participants with low to moderate myopia (≥-6.00 D) and high myopia (<-6.00 D) showed positive effects of steroids on prevention of myopia regression. In conclusion, long-term topical steroid application after PRK seems unnecessary in low and moderate myopia. New randomized clinical trials using current technologies are recommended for postoperative treatments.

Keratoconus detection by novel indices in patients with Down syndrome: a cohort population-based study.

PURPOSE: To use novel indices to determine the prevalence of KC and its progression in patients aged 10-30 years with Down syndrome. STUDY DESIGN: Cohort population-based study. METHODS: Two hundred twenty-six of 250 invited Down syndrome patients were enrolled. The diagnostic criteria were confirmed by two independent expert examiners using slit-lamp examinations and topographic indices measured by Pentacam HR (Oculus Optikgeräte): maximum keratometry centered on the steepest point (zonal Kmax-3 mm), Ambrósio's relational thickness (ART), inferior-superior asymmetry (IS-value), Belin/Ambrósio deviation value (BAD-D), the Tomographic and Biomechanical Index (TBI), and a posterior elevation map. In the KC cases, Corvis ST (Oculus Optikgeräte) was done. All the KC cases completed the second phase in 2017. RESULTS: KC was identified in 28 patients (12.39%; 95% confidence interval: 8.2-17.9%): 20 bilateral and eight unilateral cases. Of these, 24 were in the ≤ 20-years age group, and four, in the > 20-years age group. The frequency of KC was not significantly correlated with age (P = 0.804) or gender (P = 0.322). In the KC cases, the mean zonal Kmax-3 mm, ART-max, IS-value, BAD-D, CBI, and TBI were 50.40 ± 5.88 D, 321.63 ± 111.94 µm, 1.99 ± 2.51, 3.73 ± 3.12, 0.54 ± 0.61, and 0.86 ± 0.20, respectively, and the minimum corneal thickness was 492.17 ± 42.67 µm. Of the 28 patients, 39.6% showed progression, and all were in the ≤ 20-years age group. CONCLUSION: The prevalence of KC in Down syndrome patients is significantly higher than that reported in non-Down syndrome individuals of the same age groups. The progression rate is approximately similar to that of the non-Down syndrome population. Screening programs should be applied to prohibit serious visual impairment in these populations.

Multipoint assessment of demarcation line depth after standard and accelerated cross-linking in central and inferior keratoconus.

PURPOSE: To determine the changes in the depth of the demarcation line in the central to peripheral cornea following accelerated compared to standard corneal cross-linking (CXL). METHODS: In this prospective, non-randomized study, 60 eyes with progressive keratoconus underwent accelerated or standard CXL (30 in each group). Anterior segment optical coherence tomography (AS-OCT) was done one month later by two independent masked examiners to measure the depth of the demarcation line in the central cornea and on peripheral rings. RESULTS: The inter-examiner agreement (intra-class correlation coefficient) was >0.75 for all measured points, and average measurements were used in the analysis. The depth of the visualized demarcation line in the center was 223.4 ± 67.4 µm and 354.9 ± 79.0 µm in the accelerated and standard groups, respectively (P < 0.001). The depth significantly decreased from the center to the 7 mm ring in both groups (all P < 0.05). This change was 7.7-26.1% and 2.2%-11.1% in the accelerated and standard groups, respectively. In the accelerated group, the demarcation line was deeper in the central cone sub-group compared to the inferior cone sub-group, but in the standard group, the demarcation line was deeper in the inferior cone sub-group (all P < 0.05). Cases with an inferior cone showed greater inter-group differences in all studied points. CONCLUSIONS: The depth of the demarcation line with accelerated CXL is less than the standard protocol and decreases from the center towards the periphery. Demarcation lines are more homogenized with standard CXL. In cases with an inferior cone, demarcation line depth varies throughout the cornea.

One Year Outcomes of Photorefractive Keratectomy with the Application of Mitomycin-C in the Treatment of Mild to Moderate Hyperopia.

PURPOSE: To evaluate refractive and visual outcomes of photorefractive keratectomy with mitomycin-C. (PRK-MMC) for the treatment of mild to moderate hyperopia. MATERIALS AND METHODS: This case series enrolled 21 patients with up to +5.50 diopters (D) of hyperopia. All 42 eyes were treated with the Concerto (Wavelight) or the Technolas 217-Z (Bausch and Lomb) excimer laser. Outcome measures included best corrected distance vision acuity (BCVA) and uncorrected distance vision correction and refraction at 1, 3, 6, and 12 months postoperatively. RESULTS: Mean patient age was 44.8 ± 11.3 years. Preoperatively, mean manifest refractive spherical equivalent (MRSE) was + 2.00 D ± 0.76 D and mean spherical refractive error was + 2.57 D ± 0.87 D (range, +1.25 D to + 5.50 D). At 12 months postoperatively, mean MRSE was + 0.1 D ± 0.61 D. MRSE was within ± 0.50 D of emmetropia in 29 eyes (69%), and 18 eyes (43%) had 20/20 uncorrected distant visual acuity. BCVA increased by two lines or more in three eyes (7.1%) and one line in two eyes (4.7%); 31 eyes showed no change, three eyes (7.1%) lost one line, and three other eyes (7.1%) lost two lines of BCVA. No eyes lost more than two lines of BCVA. Complications included Grade 2 peripheral haze in two eyes which cleared by 12 months postoperatively. CONCLUSION: PRK-MMC was a safe and predictable method for the correction of mild to moderate hyperopia.

Long-term Results of an Accelerated Corneal Cross-linking Protocol (18 mW/cm2) for the Treatment of Progressive Keratoconus.

PURPOSE: To compare the long-term outcomes of accelerated and standard corneal cross-linking protocols in the treatment of progressive keratoconus. DESIGN: Prospective randomized clinical trial. METHODS: Thirty-one eyes with keratoconus were treated with an accelerated protocol (18 mW/cm(2), 5 min) and all contralateral eyes were treated with the standard method (3 mW/cm(2), 30 min) using the same overall fluence of 5.4 J/cm(2). RESULTS: At 18 months after the procedure, the standard group showed significant improvement in spherical equivalent (P < .05), K-readings (P < .05), Q value (P < .05), index of surface variance (P < .05), and keratoconus index (P = .008) and decline in central corneal thickness (P < .05), but no significant change in visual acuity, corneal hysteresis, corneal resistance factor, P2 area, or endothelial cell density. In the accelerated group, central corneal thickness was the only parameter with statistically significant change. However, neither of these parameters showed significant differences between the standard and the 18 mW/cm(2) accelerated protocol, except K-reading (P = .059) and index surface variance (P = .034). CONCLUSION: An accelerated cross-linking protocol, using 18 mW/cm(2) for 5 minutes, shows a comparable outcome and safety profile when compared to the standard protocol, but better corneal flattening is achieved with the standard method than the accelerated method. Overall, both methods stop the disease progression similarly. This study will continue to examine more long-term results.

Short-term comparison of accelerated and standard methods of corneal collagen crosslinking.

PURPOSE: To compare the 6-month results of accelerated and standard collagen crosslinking (CXL) treatment of progressive keratoconus. SETTING: Noor Eye Hospital, Tehran, Iran. DESIGN: Prospective randomized clinical trial. METHODS: Two groups of eyes (intervention and control) received corneal collagen crosslinking (CXL) treatment. The intervention group received accelerated CXL (18 mW/cm(2), 5 minutes), and the control group received standard CXL (3 mW/cm(2), 30 minutes). The eyes were evaluated for changes in the visual indices, refraction, and topography preoperatively and 1, 3, and 6 months postoperatively and regarding corneal rigidity indices and the endothelial cell count (ECC) preoperatively and at 6 months. RESULTS: The study evaluated 62 eyes (31 patient) in 2 groups. The mean changes in uncorrected (P = .733) and corrected (P = .646) distance visual acuities and manifest refraction spherical equivalent (P = .598) did not differ statistically significantly between the 2 groups. The central corneal thickness was higher in the standard group than the accelerated group (P = .025). The mean decrease in the maximum keratometry (K) (P = .865) and mean K (P = .974) and the mean changes in the asphericity (P = .272) were not statistically significantly different between the 2 groups. The mean changes in corneal hysteresis (CH) (P = .548) and the corneal resistance factor (CRF) (P = 1.000), CH-CRF (P = .282), and the area under the peak 2 (P = .260) were similar in both groups. The mean decrease in the ECC was not statistically significantly different between the 2 groups (P = .218). CONCLUSION: Based on 6-month results, accelerated and standard corneal CXL arrested the progression of keratoconus similarly. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Clinical results with two different pharmaceutical preparations of riboflavin in corneal cross-linking: an 18-month follow up.

BACKGROUND: Comparison of long-term clinical results of two different pharmaceutical formulations used in corneal cross-linking (CXL) in keratoconus patients. METHODS: Sixty eyes of 60 keratoconus patients underwent CXL in two groups. We used riboflavin preparations from Sina Darou, Iran in group A, and Streuli Pharma, Switzerland in group B. Here we made inter-group comparison of changes in vision, refraction, Pentacam indices, corneal biomechanical indices, and endothelial cell count (ECC) 18 months after CXL. RESULTS: Since four patients were lost to follow-up, 56 eyes (28 eyes in each group) were compared. Mean improvement in uncorrected visual acuity (UCVA) was 0.31 ± 0.65 LogMAR (P=0.014) in group A and 0.24 ± 0.62 LogMAR (P=0.082) in group B. Best corrected visual acuity (BCVA) remained quite unchanged in both groups (P=0.774). Mean spherical refractive error reduced by 0.45 ± 1.15 diopter (D) (P=0.041) in group A and 0.27 ± 1.73 D (P=0.458) in group B (P=0.655). Cylinder error and spherical equivalent had a similar trend without any change. Max-K (P=0.006) and mean-K (P=0.044) decreased significantly more in group A compared to group B. The reduction in CCT was significantly more in group A than group B (P=0.004). Q-value was quite unchanged in both groups (P=0.704). The inter-group difference in CH reduction was borderline significant statistically (P=0.057). Changes in corneal resistance factor and endothelial cell count were not significantly different between two groups (P=0.117 and P=0.229). CONCLUSION: Clinical results of CXL with the domestic preparation of riboflavin are similar to that achieved with the Swiss made product in some aspects, and it is the preferred brand in some other aspects. This study will continue to report longer follow-up results. TRIAL REGISTRATION: IRCT201212034333N2.

Comparison of clinical results of two pharmaceutical products of riboflavin in corneal collagen cross-linking for keratoconus.

BACKGROUND: To compare the 6-month results of two formulations of Riboflavin provided by Sina Darou, Iran, and Uznach, Switzerland, in corneal collagen cross-linking (CXL) for keratoconus patients. FINDINGS: Considering the results of the previous study about the similarity of the formulations and the active ingredients of the two types of Riboflavin, they were used in the CXL procedure of 60 keratoconic eyes (30 eyes in each group). After 6 months, the mean improvement of UCVA (0.239), BCVA (0.707), and MRSE (0.513) did not differ significantly between the two groups. The mean decrease in max- K (0.731), mean- K (0.264), central corneal thickness (0.759), and Q-value (0.669) did not show any significant difference between the two groups. The two groups had no significant difference in endothelial cell count decrease (0.229). The Sina Darou formulation decreased corneal hysteresis more than the Swiss formulation (P = 0.057) but there were no significant differences in the mean decrease of corneal resistance factor between the two groups (P = 0.117). CONCLUSIONS: Based on the early results, the results of visual acuity, refraction, and corneal topography using Sina Darou and Uznach formulations of Riboflavin showed that both were effective in CXL. However, considering the relatively significant difference in corneal hysteresis changes between the two groups, this study will continue to report the long-term results.

Corneal collagen cross-linking with riboflavin and ultraviolet a irradiation for keratoconus: long-term results.

PURPOSE: To evaluate the long-term results of corneal collagen cross-linking (CXL) in patients with progressive keratoconus. DESIGN: Prospective case series. PARTICIPANTS: This study was conducted on 40 eyes of 32 patients with progressive keratoconus between 2006 and 2012. METHODS: Patients underwent CXL no later than 1 month after baseline examinations. For CXL, ultraviolet irradiation was applied for 30 minutes, during which riboflavin instillation was repeated every 3 minutes. MAIN OUTCOME MEASURES: Patients were tested for best-corrected visual acuity (BCVA), uncorrected visual acuity (UCVA), manifest refraction spherical equivalent (MRSE), and Scheimpflug imaging from which we extracted maximum keratometry reading (max-K), average of minimum and maximum keratometry readings (mean-K), central corneal thickness (CCT), and anterior and posterior elevation at the apex at baseline, at 1, 3, 6 months after CXL, and 1, 2, 4, and 5 years later. We studied results at 5 years after CXL as well as the trend of changes over the 5-year period. RESULTS: Mean UCVA was 0.67 ± 0.52 logarithm of the minimum angle of resolution (logMAR) at baseline and 0.65 ± 0.51 logMAR at 5 years after the procedure. For mean BCVA, these values were 0.31 ± 0.28 and 0.19 ± 0.20 logMAR, respectively (P = 0.016). The mean MRSE changed from -3.18±2.23 diopters (D) to -2.77 ± 2.18 D, and mean refractive cylinder error changed from -3.14 ± 2.22 to -2.49 ± 1.71 D (P = 0.089). Mean max-K and mean-K decreased by 0.16 ± 2.20 and 0.10 ± 1.69 D, respectively. The CCT increased from 483.87 ± 29.07 to 485.95 ± 28.43 µm. Mean anterior elevation at the apex changed from 13.9 2 ± 8.28 to 11.45 ± 8.18 µm (P = 0.030) and posterior elevation at this point changed from 29.54 ± 18.39 to 26.34 ± 19.59 µm. The mean-K, max-K, UCVA, and astigmatism showed no change over time during these 5 years. After the first year, BCVA, MRSE, and CCT showed no change and stabilized, whereas elevation readings continued to decrease up to 5 years after CXL. CONCLUSIONS: Based on our 5-year results, treatment of progressive keratoconus with CXL can stop disease progression, without raising any concern for safety, and can eliminate the need for keratoplasty. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Confocal microscopy of corneal stroma and endothelium after LASIK and PRK.

PURPOSE: To compare with confocal microscopy the changes in stromal keratocyte density and endothelial cell count due to photorefractive keratectomy (PRK) and LASIK. METHODS: In this prospective study, 32 eyes (16 myopic patients) were examined with the NIDEK Confoscan 3 confocal microscope before and 6 months after PRK and LASIK. The preoperative mean myopia was -2.85+/-0.99 diopters (D) (range: -1.00 to -4.00 D) in 24 eyes that underwent PRK and -2.94+/-0.96 D (range: -2.00 to -4.25 D) in 8 eyes that underwent LASIK. Keratocyte density in the anterior and posterior stroma and the endothelial cell count were measured. Statistically significant changes were assessed using the t test. P<.05 was considered statistically significant. RESULTS: Preoperative hexagonal cell percentage in the LASIK group was 52.17+/-11.43 and 51.33+/-10.98 in the PRK group. Postoperatively, the percentages were 52.96+/-7.55 and 53.34+/-10.2, respectively. Six months postoperatively, keratocyte density changed by 367.12+/-103.35 cells/mm(2) (34.7% reduction) in the anterior stroma (P<.05) and 9.25+/-28.28 cells/mm(2) (1.31% reduction) in the posterior stroma (P>.05) for the LASIK group. In the PRK group, these values were 319.71+/-83.45 cells/mm(2) (31.13% reduction) in the anterior stroma (P<.05) and 0.17+/-38.97 cells/mm(2) (0.02% reduction) in the posterior stroma (P>.05). The changes in keratocyte densities were not statistically significant between groups (P>.05). The mean number of keratocytes decreased by 37.2% in the retroablation zone of the LASIK group (P<.05). No changes were noted in endothelial cell counts. CONCLUSIONS: A significant decrease occurred in the number of stromal keratocytes in the anterior stroma. Despite differences in surgery, the change in keratocyte density and endothelial cell counts were similar between LASIK and PRK groups (P>.05).