Comparison of optical aberrations in keratoconus with scleral versus rigid gas permeable lenses.

PURPOSE: to assess optical aberrations under scleral (SL) versus rigid gas permeable (RGP) lenses in patients with keratoconus. METHODS: A prospective study including 25 eyes of 14 patients. The best-corrected visual acuity (BCVA) with corrective glasses, RGP and SL, stage of keratoconus (Amsler-Krumeich classification), minimum pachymetry, maximum keratometry, and corneal higher-order aberrations (i.e, total HOAs, coma, and trefoil) with RGP and with SL were collected. Aberrometry was performed using iTrace® aberrometer (Tracey Technologies, USA). RESULTS: 80% of the included keratoconus patients were stage 4, with a mean age of 34.3 years (±8.8). There were no significant differences in mean BCVA (logMAR) between SL and RGP. The mean BCVAs were significantly better both with SL (p < 0.0001) and RGP (p < 0.0001) compared with corrective glasses. Total HOAs (p = 0.01), coma (p = 0.003) and trefoil (p = 0.008) were significantly lower with SL compared with RGP. The BCVA decreased with the stage of keratoconus in SL (p = 0.01) and RGP (p = 0.02). The BCVA decreased with decreasing minimum pachymetry in SL (p = 0.02) and RGP (p = 0.002), and with increasing maximum keratometry in SL (p = 0.02) and RGP (p = 0.01). Significant correlations were found between BCVA, total HOAs (p = 0.008), and coma (p = 0.02) in SL. CONCLUSION: For the same keratoconus patients, total higher order, coma and trefoil optical aberrations were reduced with scleral lenses compared to rigid gas permeable lenses.

Efficacy, Safety, and Outcomes following Accelerated and Iontophoresis Corneal Crosslinking in Progressive Keratoconus.

PURPOSE: To investigate the outcomes of accelerated (A-CXL) and iontophoresis (I-CXL) corneal crosslinking in a large retrospective cohort with progressive keratoconus. METHODS: This retrospective observational cohort study included consecutive patients treated by A-CXL (9 mW/5.4 J/cm2) or I-CXL with a minimal follow-up of 12 months. Visual acuity, manifest refraction, topography, specular microscopy, and corneal optical coherence tomography (OCT) were evaluated at baseline and at the last visit. Progression was defined as an increase in the maximum topographic keratometry (Kmax) of 1D. RESULTS: 302 eyes of 241 patients with a mean age of 25.2 ± 7.5 years were included from 2012 to 2019: 231 and 71 eyes in the A-CXL and I-CXL groups, respectively. The mean follow-up was 27.2 ± 13.2 months (maximum: 85.7 months). Preoperatively, the mean Kmax was 51.8 ± 4.0D, with no differences between groups. Mean topographic measurements and spherical equivalent remained stable during the follow-up. At the last visit, CXL failure was reported in 60 eyes (19.9%): 40 (14.7%) versus 20 (28.2%) in A-CXL versus I-CXL, respectively, p = 0.005. The likelihood of progression after CXL was significantly higher following I-CXL: RR = 1.62, CI95 = [1.02 to 2.59], p = 0.04. Demarcation line presence at 1 month was positively correlated with higher efficacy of CXL, p = 0.03. No endothelial damage was reported, especially in 51 thin corneas (range = 342-399 µm). CONCLUSIONS: A-CXL seems more effective than I-CXL in stabilizing keratoconus; this is to be taken into account when a therapeutic indication is posed according to the aggressiveness of the keratoconus.

Asymmetric Intrastromal Corneal Ring Segments with Progressive Base Width and Thickness for Keratoconus: Evaluation of Efficacy and Analysis of Epithelial Remodeling.

Purpose: The aim of this study is to describe visual outcomes and epithelial remodeling following the implantation of asymmetric intracorneal ring segments (ICRSs) of variable thickness and base width for the management of duck-type keratoconus. Methods: A prospective observational study of patients with duck-type keratoconus was conducted. All patients received one ICRS AJL PRO + implant (AJL Ophthalmic). We analyzed demographic and clinical data, anterior segment optical coherence tomography (AS-OCT) data and Scheimpflug camera images obtained with a Placido disc MS-39 (CSO, Firenze, Italy) one and six months after surgery to determine keratometric and aberrometric outcomes and epithelial remodeling. Results: We studied 33 keratoconic eyes. ICRS implantation significantly improved both corrected distance visual acuity (CDVA) and uncorrected distance visual acuity at six months, as assessed with the logMAR (minimum angle of resolution) system, from 0.32 ± 0.19 to 0.12 ± 0.12 (p < 0.001) and from 0.75 ± 0.38 to 0.37 ± 0.24 (p < 0.001), respectively. Overall, 87% of implanted eyes gained ≥ 1 line of CDVA, and 3% of patients (n = 1) lost one line of CDVA; 55% of eyes attained a manifest refraction spherical equivalent between +1.50 and -1.50 D. Epithelial remodeling was greater at the wider and thicker end (+11.33 µm ± 12.95; p < 0.001 relative to the initial value) than at the narrower and thinner end (+2.24 µm ± 5.67; p = 0.01). Coma aberration was significantly reduced from 1.62 ± 0.81 µm to 0.99 ± 0.59 µm (p < 0.001). Conclusions: AJL-PRO + ICRS implantation for duck-type keratoconus improves refractive, topographic, aberrometric and visual parameters and induces progressive epithelial thickening along the segment.

Full-field Optical Coherence Microscopy for Histology-like Analysis of Stromal Features in Corneal Grafts.

The quality of donor corneal stroma, which makes up about 90% of total corneal thickness, is likely to be one of the main, if not the major, limiting factor(s) for success of deep anterior lamellar and penetrating keratoplasty. These are surgical procedures that involve replacing part or all of the diseased corneal layers, respectively, by donated tissue, the graft, taken from a recently deceased individual. However, means to evaluate stromal quality of corneal grafts in eye banks are limited and lack the capability of high-resolution quantitative assessment of disease indicators. Full-field optical coherence microscopy (FF-OCM), permitting high-resolution 3D imaging of fresh or fixed ex vivo biological tissue samples, is a non-invasive technique well suited for donor cornea assessment. Here we describe a method for the qualitative and quantitative analysis of corneal stroma using FF-OCM. The protocol has been successfully applied to normal donor corneas and pathological corneal buttons, and can be used to identify healthy and pathologic features on both the macroscopic and microscopic level, thereby facilitating the detection of stromal disorders that could compromise the outcome of keratoplasty. By improving the graft quality control, this protocol has the potential to result in better selection (and rejection) of donor tissues and hence decreased graft failure.

Comparative Study of Asymmetric Versus Non-asymmetric Intrastromal Corneal Ring Segments for the Management of Keratoconus.

PURPOSE: To compare the outcomes obtained with models of asymmetric and non-asymmetric intracorneal ring segments (ICRS) in keratoconic eyes with asymmetric topo-graphic patterns. METHODS: In this prospective observational study, ICRS were implanted alternately in patients with the same tomographic patterns of keratoconus assigned to four groups. Patients with the "duck" phenotype received one asymmetric or non-asymmetric ICRS and patients with the "snowman" pheno-type received two asymmetric or non-asymmetric ICRS. Visual, refractive, astigmatism, keratometric, and corneal aberrometry changes were evaluated over a 6-month follow-up period. RESULTS: Sixty-eight eyes were analyzed. No significant difference was observed between the use of one asymmetric and one non-asymmetric ICRS in duck phenotypes. In snowman keratoconus, the inferior-superior index decreased significantly (P = .03) with asymmetric but not with non-asymmetric ICRS implantation. Total corneal higher order aberrations and coma rates were lower, but not significantly so, after the implantation of two asymmetric ICRS in snowman phenotypes (2.85 ± 0.89 to 2.60 ± 0.91 µm, P = .20 and 2.64 ± 0.93 to 2.39 ± 0.98 µm, P = .21), and significantly higher after the implantation of two non-asymmetric ICRS (2.56 ± 1.28 to 3.08 ± 1.62 µm, P = .02 and 2.34 ± 1.27 to 2.84 ± 1.62 µm, P = .02). CONCLUSIONS: Asymmetric ICRS did not improve the outcomes of ICRS implantation in duck keratoconus. However, the implantation of two asymmetric ICRS was more effective than that of two non-asymmetric ICRS for decreasing vertical asymmetry and preventing increases in corneal aberration in the snowman phenotype of keratoconus. [J Refract Surg. 2021;37(8):552-561.].

Postoperative Corneal Epithelial Remodeling After Intracorneal Ring Segment Procedures for Keratoconus: An Optical Coherence Tomography Study.

PURPOSE: To assess epithelial corneal remodeling by anterior segment optical coherence tomography (AS-OCT) after intracorneal ring segments (ICRS) implantation in keratoconic eyes. METHODS: This prospective observational study included patients with keratoconus receiving ICRS of different arc lengths according to their tomographic pattern. AS-OCT and corneal topography (Scheimpflug camera) were performed before and 1, 3, and 6 months after surgery. Corneal pachymetry mapping was performed and total corneal and epithelial thicknesses (3-mm central and 16 points on 6-mm zone) were measured over the pupil center using AS-OCT. Topographic parameters were also assessed. RESULTS: A total of 68 keratoconic eyes were analyzed (Amsler-Krumeich stages 1 to 4) in four groups of 17 eyes: 210° ICRS, 320° ICRS, double 160° ICRS, and single 160° ICRS. Corneal pachymetry mapping revealed that epithelial thickness increased significantly in the internal zones juxtaposed to the ICRS without smoothing during the postoperative period (P < .05). Mean maximum epithelial thickness increased from 67 ± 6 to 79 ± 7 µm for 210° ICRS, 66 ± 9 to 82 ± 4 µm for 320° ICRS, 63 ± 6 to 78 ± 7 µm for double 160° ICRS, and 62 ± 5 to 77 ± 5 µm for single 160° ICRS (P < .0001). Significant epithelial thickening at the apex of the cone was observed in all groups (P < .05). CONCLUSIONS: Significant epithelial thickening occurs after ICRS implantation adjacent to the ICRS to compensate for the ridge created with a thickening of epithelium over the cone due to regularization of the stromal surface. [J Refract Surg. 2021;37(6):404-413.].

Long-Term Results and Refractive Error After Cataract Surgery With a Scleral Incision in Eyes With Deep Anterior Lamellar Keratoplasty.

PURPOSE: Phacoemulsification in eyes with deep anterior lamellar keratoplasty (DALK) is associated with possible decreased graft survival and difficult IOL power calculation. We assessed cataract surgery in eyes with previous DALK. METHODS: Thirty-three consecutive eyes with DALK and further phacoemulsification with scleral incision were included in this retrospective study. At each postoperative visit, eyes were assessed with manifest refraction, optical coherence tomography, specular corneal topography, and noncontact wide-field specular microscopy. RESULTS: The average postkeratoplasty follow-up time was 102 months [95%-CI, (85-119)]. Cataract surgery was performed on average 43 months (30-56) after DALK. The average postphacoemulsification follow-up time was 58 months [42-74]. All grafts remained clear during follow-up. The best spectacle-corrected logarithm of the minimum angle of resolution visual acuity improved by 2.5 lines [1.8-3.1] on average after cataract surgery from 0.58 (20/77) to 0.34 (20/44) (P < 0.001). The spherical equivalent and intraocular pressure significantly improved from -4.1 D to -1.7 D and from 15.9 to 14.0 mm Hg, respectively. The corneal central thickness was not significantly modified, and the endothelial density decreased by 5.3% from 2081 to 1970 cells/mm2 (P = 0.003). The minimal difference between the achieved and predicted spherical equivalents [-0.05 D, (-2.33; +2.21)] was obtained with the Hoffer Q formula using the IOLMaster axial length and the Orbscan keratometry. CONCLUSIONS: Patients with DALK who underwent phacoemulsification with a scleral incision had a satisfying residual refractive error, very high graft survival, and very few complications. The Hoffer Q formula with the IOLMaster axial length and the specular corneal topography keratometry seems to be the most accurate for IOL calculation.

Corneal stromal stem cells restore transparency after N2 injury in mice.

Corneal scarring associated with various corneal conditions is a leading cause of blindness worldwide. The present study aimed to test the hypothesis that corneal stromal stem cells have a therapeutic effect and are able to restore the extracellular matrix organization and corneal transparency in vivo. We first developed a mouse model of corneal stromal scar induced by liquid nitrogen (N2 ) application. We then reversed stromal scarring by injecting mouse or human corneal stromal stem cells in injured cornea. To characterize the mouse model developed in this study and the therapeutic effect of corneal stromal stem cells, we used a combination of in vivo (slit lamp, optical coherence tomography, in vivo confocal microscopy, optical coherence tomography shear wave elastography, and optokinetic tracking response) and ex vivo (full field optical coherence microscopy, flow cytometry, transmission electron microscopy, and histology) techniques. The mouse model obtained features early inflammation, keratocyte apoptosis, keratocyte transformation into myofibroblasts, collagen type III synthesis, impaired stromal ultrastructure, corneal stromal haze formation, increased corneal rigidity, and impaired visual acuity. Injection of stromal stem cells in N2 -injured cornea resulted in improved corneal transparency associated with corneal stromal stem cell migration and growth in the recipient stroma, absence of inflammatory response, recipient corneal epithelial cell growth, decreased collagen type III stromal content, restored stromal ultrastructure, decreased stromal haze, decreased corneal rigidity, and improved vision. Our study demonstrates the ability of corneal stromal stem cells to promote regeneration of transparent stromal tissue after corneal scarring induced by liquid nitrogen.

Long-Term Results of Cultured Limbal Stem Cell Versus Limbal Tissue Transplantation in Stage III Limbal Deficiency.

We aimed to evaluate efficiency and safety of transplantation of limbal stem cells (LSC) cultured on human amniotic membrane with no feeders and to compare cultured LSC with limbal tissue transplantation. Thirty eyes with stage III LSC deficiency were treated with autologous (autoLSC) or allogeneic (alloLSC) cultured LSC transplantation (prospective phase II clinical trial; average follow-up time, 72 months) or autologous (autoLT) or allogeneic (alloLT) limbal tissue transplantation (retrospective control group; average follow-up time, 132 months) between 1993 and 2014. The 5-year graft survival defined by absence of recurrence of the clinical signs of limbal deficiency was 71% for autoLSC, 0% for alloLSC, 75% for autoLT, and 33% for alloLT. Visual acuity improved by 9.2 lines for autoLSC and 3.3 lines for autoLT. It decreased by 0.7 lines for alloLSC and 1.9 lines for alloLT. Adverse events were recorded in 1/7 autoLSC, 7/7 alloLSC, 6/8 autoLT, and 8/8 alloLT patients. Corneal epithelial defect was the only adverse event recorded after autoLSC, whereas severe sight-threatening adverse events were recorded in the remaining three groups. Compared with failed grafts, successful grafts featured greater decrease in fluorescein staining, greater superficial vascularization-free corneal area, lower variability of the corneal epithelial thickness, and higher corneal epithelial basal cell density. Autologous cultured LSC transplantation was associated with high long-term survival and dramatic improvement in vision and was very safe. Autologous limbal tissue transplantation resulted in similar efficiency but was less safe. Cadaver allogeneic grafts resulted in low long-term success rate and high prevalence of serious adverse events. Stem Cells Translational Medicine 2019;8:1230&1241.

Stromal striae: a new insight into corneal physiology and mechanics.

We uncover the significance of a previously unappreciated structural feature in corneal stroma, important to its biomechanics. Vogt striae are a known clinical indicator of keratoconus, and consist of dark, vertical lines crossing the corneal depth. However we detected stromal striae in most corneas, not only keratoconus. We observed striae with multiple imaging modalities in 82% of 118 human corneas, with pathology-specific differences. Striae generally depart from anchor points at Descemet's membrane in the posterior stroma obliquely in a V-shape, whereas in keratoconus, striae depart vertically from posterior toward anterior stroma. Optical coherence tomography shear wave elastography showed discontinuity of rigidity, and second harmonic generation and scanning electron microscopies showed undulation of lamellae at striae locations. Striae visibility decreased beyond physiological pressure and increased beyond physiological hydration. Immunohistology revealed striae to predominantly contain collagen VI, lumican and keratocan. The role of these regions of collagen VI linking sets of lamellae may be to absorb increases in intraocular pressure and external shocks.

New parameters in assessment of human donor corneal stroma.

PURPOSE: To provide quantitative parameters for assessment of human donor corneal stroma by imaging stromal features of diseased and normal human corneas with full-field optical coherence microscopy (FFOCM), using confocal microscopy (CM) and histology as reference techniques. METHODS: Bowman's layer (BL) thickness and keratocyte density were assessed ex vivo in 23 human donor corneas and 27 human pathological corneas (keratoconus and other corneal disorders) with FFOCM, CM and histology. Stromal backscattering was assessed with FFOCM. Additionally, 10 normal human corneas were assessed in vivo with CM. RESULTS: In FFOCM, the logarithm of the normalized stromal reflectivity was a linear function of stromal depth (R2  = 0.95) in human donor corneas. Compared with keratoconus corneas, human donor corneas featured higher BL thickness (p = 0.0014) with lower coefficient of variation (BL-COV; p = 0.0002), and linear logarithmic stromal reflectivity with depth (higher R2 , p = 0.0001). Compared with other corneal disorders, human donor corneas featured lower BL-COV (p = 0.012) and higher R2 (p = 0.0001). Using the 95% confidence limits of the human donor cornea group, BL thickness < 6.5 µm (sensitivity, 57%; specificity, 100%), BL-COV > 18.6% (79%; 100%) and R2  < 0.94 (93%; 71%) were revealed as indictors of abnormal cornea. In CM, keratocyte density decreased with stromal depth (r = -0.56). The mean overall keratocyte density (cells/mm2 ) was 205 in human donor corneas, 244 in keratoconus, 176 in other corneal disorders and 386 in normal corneas. CONCLUSION: Full-field optical coherence microscopy (FFOCM) provides precise and reliable parameters for non-invasive assessment of human donor corneal stroma during storage, enabling detection of stromal disorders that could impair the results of keratoplasty.

Imaging Microscopic Features of Keratoconic Corneal Morphology.

PURPOSE: To search for gold-standard histology indicators using alternative imaging modalities in keratoconic corneas. METHODS: Prospective observational case-control study. Fourteen keratoconic corneas and 20 normal corneas (10 in vivo healthy subjects and 10 ex vivo donor corneas) were examined. Images of corneas were taken by spectral domain optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM) before keratoplasty. The same removed corneal buttons were imaged after keratoplasty with full-field optical coherence microscopy (FFOCM) and then fixed and sent for histology. Controls consisted of normal subjects imaged in vivo with IVCM and donor corneas imaged ex vivo with FFOCM. Corneal structural changes related to pathology were noted with each imaging modality. Cell density was quantified by manual cell counting. RESULTS: Keratoconus indicators (ie, epithelial thinning/thickening, cell shape changes, ferritin deposits, basement membrane anomalies, Bowman layer thinning, ruptures, interruptions, scarring, stromal modifications, and appearance of Vogt striae) were generally visible with all modalities. Additional features could be seen with FFOCM in comparison with gold-standard histology, particularly in the Bowman layer region, whereas the combination of SD-OCT plus IVCM detected 76% of those features detected in histology. Three-dimensional FFOCM imaging aided interpretation of two-dimensional IVCM and SD-OCT data. Basal epithelial cell and keratocyte densities were significantly lower in patients with keratoconus than those in normals (P < 0.0001). CONCLUSIONS: Structural and cellular assessment of the keratoconic cornea by means of either in vivo SD-OCT combined with IVCM or ex vivo FFOCM in both cross-sectional and en face views can detect as many keratoconus indicators as gold-standard histology.

Corneal radius of curvature after anterior lamellar versus penetrating keratoplasty.

BACKGROUND: Keratoplasty may induce major spherical refractive error related to abnormal corneal radius of curvature (CRC). METHODS: Two hundred and thirty-eight consecutive eyes of 238 patients with clear graft and at least one postoperative Orbscan examination performed after suture removal (average follow-up time, 86 months) were retrospectively analyzed. Anterior lamellar keratoplasties (ALK group, n = 119) and penetrating keratoplasties (PK group, n = 119) were matched for preoperative diagnosis and lens status. RESULTS: The average postoperative, suture-out, Orbscan 3-mm CRC was 7.17 mm with a wide 95 % confidence interval [6.26 mm; 8.37 mm]. It was 7.05 mm in the ALK group and 7.31 mm in the PK group (p < 0.01). In the ALK group, this figure was 7.00 mm for oversized grafts and 7.67 mm for non-oversized grafts (p < 0.001). CRC values were significantly lower for eyes with keratoconus (7.00 mm) or stromal scar after infectious keratitis (7.06 mm) compared with stromal scar after trauma (7.74 mm) or stromal dystrophies (8.17 mm). Values were significantly lower for big-bubble ALKs (6.92 mm) and manual dissection-ALKs (7.14 mm) compared with PKs (7.31 mm) and microkeratome-assisted ALKs (7.45 mm). The average Orbscan 3-mm SimK cylinder, irregularity, and refractive power symmetry index were, respectively, 4.7 D/4.8 D/1.9 D for ALKs and 5.2 D/4.8 D/1.8 D for PKs (p = 0.99). CONCLUSIONS: The CRC is lower after ALK compared with PK, and features important variability. In eyes with ALK, non-oversized grafts result in postoperative CRC close to normal values and corneal diseases associated with stromal thinning and DALK result in lower postoperative CRC.