Corneal Epithelial Remodeling in a 6-Month Follow-up Period in Myopic Corneal Refractive Surgeries.

PURPOSE: To investigate corneal epithelial thickness changes during a 6-month follow-up period after transepithelial photorefractive keratectomy (tPRK), femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), and small incision lenticule extraction (SMILE). METHODS: This prospective study included 76 eyes of 76 participants who underwent myopic refractive surgery (23 FS-LASIK, 22 SMILE, and 31 tPRK). Epithelial thickness and anterior curvature were averaged over 4 regions (subdivided into 25 areas) and measured by spectral-domain optical coherence tomography and Scheimpflug tomography before the operation (pre) and at 1 or 3 days (pos1-3d), 1 week (pos1w), and 1 month (pos1m), 3 months (pos3m), and 6 months (pos6m) postoperatively. RESULTS: The epithelial thickness of the three groups was similar in both the pre and pos6m (all P > .05), but the tPRK group fluctuated the most during the follow-up period. The largest increase was in the inferior-temporal paracentral area (7.25 ± 2.58 µm for FS-LASIK; 5.79 ± 2.41 µm for SMILE; 4.88 ± 5.84 µm for tPRK; all P < .001). Only the epithelial thickness of tPRK increased from pos3m to pos6m (P < .05), whereas all changes for FS-LASIK and SMILE were not significant (P > .05). A positive correlation of thickness changes with curvature gradient in the paracentral region of tPRK was found (r = 0.549, P = .018), but not in other regions in all groups. CONCLUSIONS: Epithelial remodeling followed different trends after different surgeries from the early postoperative stage onward, but exhibited similar values at pos6m. Although remodeling after FS-LASIK and SMILE stabilized by pos3m, it remained unstable at pos6m after tPRK. These changes may affect corneal profile and lead to deviation from the intended surgical outcome. [J Refract Surg. 2023;39(3):187-196.].

Long-Term Outcome of Femtosecond Laser-Assisted Keratopigmentation: Using Intacs Channels for Precise Pigment Deposition Within the Cornea.

PURPOSE: To describe a long-term outcome of a new technique using the femtosecond laser to assist with keratopigmentation (corneal tattooing). METHOD: Nineteen eyes of 18 patients with a history of significant visual disability related to iris defects underwent femtosecond laser-assisted keratopigmentation (FAK) for functional restoration of their visual disabilities. Postoperative visual acuity and symptomatic resolution were collected during their postoperative visits. RESULTS: After FAK surgery, all patients had improvement in their previous visual-related symptoms. Eighteen of 19 eyes (94%) had improvement in their best-corrected Snellen visual acuity. Eight of 19 eyes (42%) had at least 1 line improvement, 8 of 19 eyes (42%) had at least 2 lines of improvement, and 2 of 19 eyes (10%) had at least 3 lines improvement. The average follow-up period was approximately 60 months. CONCLUSIONS: The FAK technique offers a long-term effective and safe technique for visual disabilities and improves visual acuity in patients with various traumatic iris defects.

A new collagen scaffold for the improvement of corneal biomechanical properties in a rabbit model.

Although collagen based materials are widely used in corneal tissue engineering with promising results. The usage of such materials for the improvement of corneal biomechanical properties is still unclear. In this study, we aimed to investigate a new Viscoll collagen-based membrane for the improvement of corneal biomechanical characteristics.The right eyes of 15 Chinchilla rabbits were implanted with the membrane via an intrastromal pocket, with the contralateral intact eyes as controls. At 7, 30, 90, and 180 days post-surgery, the rabbits underwent anterior segment optical coherence topography, clinical examination, and slit-lamp microscopy. Additionally, the corneal samples also underwent histological examination followed by the assessment of the biomechanical characteristics of four treated and non-treated corneas at 30, 90, and 180 days, including keratometry at 180 days, post operation. Data are presented as means ± confidence intervals with a 95% confidence level. All the operated corneas retained their transparency throughout the study. Implantation approximately doubled the central corneal thickness. Corneas became stronger by approximately 87% between 1 and 6 months after surgery (maximum fracture load, 13.3 ± 0.8 and 24.9 ± 1.4 N, respectively), and their elasticity increased by approximately 27% over the same time frame (maximum slope of the elastic region of the stress-strain curve, 11.5 ± 0.2 and 14.6 ± 1.4 N/mm respectively). We have thus proposed a new method to increase corneal thickness and strengthen the corneal tissues while preserving their transparency and demonstrated its safety and efficacy in a rabbit model over 6 months. This may be a suitable alternative to the existing corneal collagen crosslinking procedure.

Temporal evolution of the biological response to laser-induced refractive index change (LIRIC) in rabbit corneas.

Laser-induced refractive index change (LIRIC) is a new, non-incisional, non-ablative, femtosecond photo-modification technique being developed for vision correction in humans. Prior, exvivo studies showed intra-tissue refractive index change to induce minimal cell death, restricted to the laser focal zone in the corneal stroma, and with no observable damage to the epithelium or endothelium. Here, we used live rabbits to ascertain longer-term consequences of LIRIC in vivo. Specifically, we assessed cell death, fibrosis, corneal nerve distribution, endothelial cell density, and corneal structure for up to 3 months after LIRIC. A +2.5 D gradient-index LIRIC Fresnel lens was inscribed inside 20 applanated corneas of Dutch Belted rabbits, over a circular region of the mid-stroma measuring 4.5 mm in diameter. Twelve additional rabbit eyes were used as applanation-only controls to differentiate the effects of laser treatment and suction applanation on biological and structural parameters. In vivo optical measurements were performed pre-operatively, then immediately, 2, 4, and 12 weeks after the procedure, to measure endothelial cell density and changes in corneal structure. Groups of four rabbits were sacrificed at 4 hours, 2, 4, and 12 weeks after LIRIC for histological determinations; the TUNEL assay was used to evaluate cell death, H&E staining was used to assess inflammatory infiltration, and immunostaining for α-smooth muscle actin (α-SMA) and ßIII tubulin (Tuj-1) was performed to assess myofibroblast differentiation and corneal nerve distribution, respectively. Consistent with prior ex vivo data, only minimal cell death was observed in the laser focal zone, with TUNEL-positive cells restricted to the stromal region of refractive index change 4 h after LIRIC. No TUNEL-positive cells were evident anywhere in the cornea 2, 4, or 12 weeks after LIRIC. Applanation-only corneas were completely TUNEL-negative. Neither LIRIC-treated nor applanation-only eyes exhibited α-SMA-positive staining or altered corneal nerve distributions at any of the time points examined. In vivo confocal imaging revealed normal endothelial cell densities in all eyes (whether LIRIC-treated or applanation-only) at all time points. Optical coherence tomography showed suction applanation to cause a temporary decrease in central corneal thickness, which returned to normal within 4 h. Corneas into which LIRIC Fresnel lenses were written while applanated did not undergo major structural or shape changes beyond the temporary thinning already described for suction applanation. The present findings suggest that LIRIC patterns, which generated a clinically-relevant refractive correction in the mid-stromal region of live rabbit corneas, induced little-to-no disruption to corneal structure and biology for 3 months after the procedure. This affirms the relative safety of LIRIC and predicts that compared to traditional laser vision correction surgeries, common post-operative complications such as dry eye, haze, or patient discomfort may be entirely avoided.

Effect of Laser-assisted Subepithelial Keratectomy with Mitomycin C on Corneal Optical Density Measured with Confocal Microscopy.

SIGNIFICANCE: The development of confocal microscopy allows one to obtain high-resolution corneal images like its optical density. Some studies have evaluated the optical density with Scheimpflug cameras in the early post-operative period after photorefractive keratectomy, but no studies have evaluated the long-term evolution of optical density after surface ablation when mitomycin C is used. PURPOSE: This work aimed to study the changes in corneal optical density measured with confocal microscopy in eyes treated with laser-assisted subepithelial keratectomy (LASEK) and intraoperative mitomycin C (MMC) to correct myopia. METHODS: A study of 24 consecutive myopic eyes that underwent LASEK with 0.02% MMC and a control group of 24 healthy nontreated eyes was performed. Optical density was measured using the images by the confocal microscopy of the Heidelberg Retina Tomograph II with the Rostock Cornea Module. An analysis of confocal microscopy images was performed using the ImageJ software to obtain the optical density, in gray-scale units (GSU). The optical density of the stromal bed was evaluated 3 months, 15 months, and 3 years after surgery and was compared with the optical density at the equivalent depth of the stroma in controls. RESULTS: The mean values of optical density for the LASEK group were 81.7 ± 9.7, 78.6 ± 11.7, and 73.6 ± 18.7 GSU at 3 months, 15 months, and 3 years, respectively, and it was 61.8 ± 8.2 GSU for the control group. A statistically higher optical density 3 and 15 months after LASEK with MMC was found compared with controls (P < .001). No significant difference was found in optical density at 3 years post-operatively. CONCLUSIONS: Our study suggests that, after LASEK with MMC, the anterior corneal stroma has a higher optical density at 3 and 15 months post-operatively, which gradually returns to normal values 3 years after surgery.

Effect of penetration enhancer with novel corneal cross-linking using recombinant human decoron in porcine eyes.

The aim of the study was to investigate the effectiveness of exogenous recombinant human decoron and an accompanying penetration-enhancing solution in stiffening ex-vivo porcine corneas both transepithelially and after de-epithelialization. Eight porcine paired eyes were treated transepithelially: one eye with a pre-treatment solution (Pre-Tx), penetration enhancing solution (PE), and decoron while the fellow eye was treated by the same protocol but without decoron. A second group included 4 de-epithelialized pairs treated identically. The final group included 4 de-epithelialized pairs with one eye treated with Pre-Tx, PE, and decoron while the fellow eye was treated without PE. Uniaxial tensile testing was used to compare the corneal stiffness between the different treatment conditions. Residual tissue underwent immunohistochemistry analysis to evaluate the depth of penetration of decoron into the corneal stroma. There was no stiffening effect exhibited among corneas treated transepithelially with decoron compared to control (P > 0.05) and poor stromal penetration was exhibited on tissue analysis. Among de-epithelialized corneas, there was a significant stiffening effect seen in those treated with decoron at 3%, 4%, 5%, & 6% strain (P < 0.05) compared to control. Among de-epithelialized corneas there was also a significant stiffening effect seen in those treated with the PE and decoron at 4%, 5%, & 6% strain (P < 0.05) with improved stromal penetration confirmed by immunohistochemistry, versus without PE. De-epithelialization is necessary for effective stromal penetration of decoron. Depth of penetration and subsequent corneal stiffening may be improved with a penetration enhancing solution. Compared to riboflavin, decoron requires shorter treatment time and spares UV light exposure.

Exacerbation of Granular Corneal Dystrophy Type 2 After Small Incision Lenticule Extraction.

PURPOSE: To report the outcome of unilateral small incision lenticule extraction (SMILE) in a patient with granular corneal dystrophy type 2 (GCD2). METHODS: Slit-lamp photography and Fourier domain optical coherence tomography were used to document the clinical course and appearance of the corneas in a patient with genetically determined GCD2 who underwent unilateral SMILE in the right eye. RESULTS: Slit-lamp examination of a 23-year-old woman revealed 2 faint opacities at the surgical interface approximately 2 months after the SMILE procedure had been performed on her right eye. Nine and 3 typical GCD2 deposits located immediately beneath the Bowman layer were observed in the right and left corneas, respectively. Over time, the deposits at the interface increased in size, density, and number in the right eye. Fourier domain optical coherence tomography performed 33 months after the SMILE procedure revealed deposits at the SMILE interface that were distinct from those located immediately beneath the Bowman layer. The severity of disease exacerbation was less in this patient than what is typically observed in others who have undergone laser-assisted in situ keratomileusis or photorefractive keratectomy. CONCLUSIONS: SMILE is contraindicated in patients with GCD2, as are other corneal refractive surgical procedures. This case highlights the importance of genetic testing before the performance of refractive corneal procedures-especially for patients with corneal opacities on preoperative slit-lamp examination or a family history of corneal disease compatible with that of a corneal dystrophy.

Epithelial and stromal remodelling following femtosecond laser-assisted stromal lenticule addition keratoplasty (SLAK) for keratoconus.

The purpose of this study was to evaluate corneal epithelium and stromal remodelling with anterior segment optical coherence tomography in patients who have undergone stromal lenticule addition keratoplasty (SLAK) for advanced keratoconus. This was a prospective non-comparative observational study. Fifteen eyes of 15 patients with advanced keratoconus underwent implantation with a cadaveric, donor negative meniscus-shaped intrastromal lenticule, produced with a femtosecond laser, into a stromal pocket dissected in the recipient cornea at a depth of 120 µm. Simulated keratometry, central corneal thickness (CTT), corneal thinnest point (CTP), central epithelial thickness (CET), central and peripheral lenticule thickness, anterior and posterior stromal thickness were measured. Regional central corneal epithelial thickness (CET) and variations in the inner annular area (IAT) and outer annular area (OAT) were also analysed. All parameters were measured preoperatively and 1, 3, and 6 months postoperatively. The average anterior Sim-k decreased from 59.63 ± 7.58 preoperatively to 57.19 ± 6.33 D 6 months postoperatively. CCT, CTP, CET, and OAT increased and IAT decreased significantly after 1 month. All parameters appeared unchanged at 6-months except that of OAT that further increased. Lenticule thickness was stable. In conclusion we observed that SLAK reshapes the cornea by central flattening with stromal thickening and epithelial thickness restoration.

Corneal Biomechanical Properties after Small Incision Lenticule Extraction Surgery on Thin Cornea.

PURPOSE: To explore the biomechanical changes in thin corneas after the small incision lenticule extraction (SMILE) surgery. METHODS: This prospective survey screened patients scheduled for the SMILE surgery from November 2017 to March 2018. Patients with thin corneas (central corneal thickness [CCT] ≤500 µm) and those with normal corneal thickness (CCT > 500 µm) were enrolled. Corneal biomechanics were examined by the ocular response analyser and Corvis ST, preoperatively and at 1 day, 3 weeks, and 3 months postoperatively. RESULTS: Twenty-seven patients (46 eyes) with mean spherical equivalent of -5.1 ± 1.7 D were assigned to the thin cornea group, and 28 (45 eyes) cases with mean spherical equation of -5.3 ± 1.8 D were assigned to the control group. Safety and efficacy did not differ between the two age- and refraction-matched groups (safety index, 1.15 ± 0.14 vs 1.14 ± 0.17 [P = .7]; efficacy index, 1.11 ± 0.13 vs 1.16 ± 0.22 [P = .2]). All biomechanical parameters changed significantly after SMILE. The thin cornea group showed less decrease in the second applanation time (A2 Time), stiffness parameters at first applanation (SP-A1). Pooling data from two groups, lower CCT was correlated with less A2 Time change (r = 0.37, P < .01) and less SP-A1 change (r = -0.33, P < .01). Less bIOP change was correlated with higher residual stromal thickness index and thicker CCT (P = .003, R2 = 0.12). CONCLUSION: Over a short-term observation period, less corneal biomechanic deterioration may have contributed to the safety of SMILE on thin cornea.

Lower Corneal Haze and Aberrations in Descemet Membrane Endothelial Keratoplasty Versus Descemet Stripping Automated Endothelial Keratoplasty in Fellow Eyes for Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To investigate the long-term corneal changes in patients with Fuchs endothelial corneal dystrophy contributing to superior postoperative visual outcomes after Descemet membrane endothelial keratoplasty (DMEK) compared with Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Using retrospective analysis, we evaluated 9 patients with Fuchs endothelial corneal dystrophy who underwent DSAEK in 1 eye and DMEK in the fellow eye. Patients were genotyped for the triplet repeat expansion in the TCF4 gene and imaged using optical coherence tomography, Scheimpflug imaging, and in vivo confocal microscopy through focusing. RESULTS: Eight of 9 subjects were genotyped, and all were found to harbor the triplet repeat expansion. The average time between endothelial keratoplasty and imaging was 76 ± 22 and 37 ± 9 months after DSAEK and DMEK, respectively. The mean best spectacle-corrected visual acuity (logMAR) was 0.04 ± 0.05 and 0.11 ± 0.03 in the DMEK eyes versus DSAEK eyes (P = 0.02), respectively. Posterior corneal higher order aberrations were less in the DMEK eyes compared with fellow DSAEK eyes (0.25 ± 0.06 and 0.66 ± 0.25, respectively, P ≤ 0.01). Using confocal microscopy through focusing, we found that the persistent anterior stromal haze was correlated between the right and left eyes (R = 0.73, P ≤ 0.05), but total stromal backscattering was higher for the DSAEK eyes (P ≤ 0.05). CONCLUSIONS: DSAEK inherently results in higher total stromal backscattering (haze) compared with DMEK because of the addition of stromal tissue. Lower higher order aberrations of the posterior cornea and lower total stromal backscattering (haze) may both contribute to superior visual outcomes after DMEK compared with DSAEK.

Clinical outcomes of topography-guided femtosecond laser-assisted in situ keratomileusis after multifocal intraocular lens implantation.

This retrospective study is to evaluate refractive and visual outcomes of topography-guided femtosecond laser-assisted in situ keratomileusis (TGL) for correcting corneal high-order aberrations (HoA) after multifocal intraocular lens (mIOL) implantation. Twenty-eight eyes of 28 patients with both corrected distance visual acuity (CDVA) under 20/25 and subjective visual discomfort at 3 months after mIOL implantation were included in the study. TGL was performed to correct corneal HoA. Visual acuity, manifest refraction, and corneal HoA were measured 3 months after TGL. CDVA was improved in 22 (78.57%) of 28 eyes after TGL. Uncorrected distance visual acuity (0.12 ± 0.16 logMAR) and uncorrected near visual acuity (0.081 ± 0.16 logMAR) were better than those before TGL (P < 0.001). Residual refractive astigmatism showed no difference compared to that before TGL. Root mean square (RMS) of HoA (P = 0.012), spherical aberration (P = 0.013), and RMS of coma (P = 0.001) were reduced relative to those before TGL. Amount of improvement in CDVA was correlated with amount of reduced coma RMS (R = 0.524; P = 0.005) and spherical aberration (R = 0.443; P = 0.021). TGL showed to improve both refractive and visual outcomes in patients with mIOL implantation by correcting corneal HoA.

A pilot study: lenticule quality of hyperopic small incision lenticule extraction (SMILE) in rabbits.

BACKGROUND: To evaluate lenticule surface characteristics of small incision lenticule extraction (SMILE) for hyperopia correction in rabbits. METHODS: The left and right eyes of 8 rabbits were divided into two groups. The right eyes were assigned to a myopia group, and the left eyes to a hyperopia group. The rabbits received SMILE procedures with + 3.00 D and - 3.00 D correction for the hyperopia and myopia groups, respectively. Extracted lenticules were examined via scanning electron microscopy. Lenticules from odd-numbered rabbits were accessed with the anterior surface, and lenticules from even-numbered rabbits were observed with the posterior surface. A previously established scoring system was used to evaluate lenticule surface characteristics. Statistical analysis was conducted to compare the scores between the two groups. RESULTS: All procedures were performed successfully, and the lenticules were extracted smoothly. One myopia lenticule that was facing downward was handled failed in preparation for imaging, thus 15 lenticules were ultimately graded. Twelve lenticules exhibited smooth surfaces, and regularly arranged tissue bridges were observed in almost all regions. Three lenticules exhibited a partially rough surface and irregularities affecting more than 10% of the lenticules (2 in the hyperopia group and 1 in the myopia group). Rough lenticules occurred in twice as many lenticules in the hyperopia group compared to the myopia group. CONCLUSIONS: Scan quality of lenticules after SMILE for hyperopia correction is comparable to that of myopia lenticules. The shape of hyperopic lenticule may increase the difficulty of surgical manipulation and result in surface roughness.

Association Between Keratoconus and Thyroid Gland Dysfunction: A Cross-Sectional Case-Control Study.

PURPOSE: To examine the clinical association between thyroid gland dysfunction and keratoconus. METHODS: This was a cross-sectional case-control study conducted between May 2018 and July 2019. After performing Pentacam (Oculus Optikgeräte GmbH, Wetzlar, Germany) examination, flat, steep, and maximum simulated keratometric readings were recorded for each patient. Serum concentrations of free triiodothyronine, free thyroxine, and thyroid-stimulating hormone were measured. Further examinations by an endocrinologist were indicated for patients with positive laboratory results to confirm thyroid gland dysfunction. RESULTS: One hundred eighty-seven patients with bilateral keratoconus and 187 sex- and age-matched healthy controls without keratoconus were analyzed. Mean age was 26.4 ± 8.2 years for the patients with keratoconus and 27.1 ± 9.4 years for the control patients, with no significant difference. The results showed that thyroid gland dysfunction prevalence was 10 of 187 patients with keratoconus (5.3%) and 2 of 187 control patients (1.1%), and the difference was statistically significant (P = .036). For the patients with keratoconus and thyroid gland dysfunction, 8 were women and 2 were men. Additionally, 6 patients (2 men and 4 women) had hyperthyrosis and 4 women had hypothyrosis. For controls, the two patients had hypothyrosis. CONCLUSIONS: This study showed that there is a possible association between keratoconus and thyroid gland dysfunction, but more studies are needed to build upon these results. [J Refract Surg. 2020;36(4):253-257.].

Astigmatism prediction in small-incision lenticule extraction.

PURPOSE: To investigate whether postoperative-induced refractive astigmatism after small-incision lenticule extraction (SMILE) could be predicted by preoperative objective astigmatism measured with autorefraction, keratometry, and Scheimpflug tomography. SETTING: University eye clinic. DESIGN: Retrospective case series. METHODS: Only eyes without preoperative subjective astigmatism treated with SMILE for myopia were included. Postoperative subjective astigmatism was compared with preoperative objective astigmatism. Examinations were performed before SMILE and 3 months postoperatively and included subjective refraction, keratometry, autorefraction, and Scheimpflug tomographer measurements. Astigmatism was analyzed using double-angle plots and multivariate statistics. RESULTS: A total of 358 eyes of 358 patients were included. The mean preoperative sphere was -7.33 diopter (D) ± 1.46 (SD). The postoperative spherical equivalent was -0.30 ± 0.49 D. Postoperatively, 79.6% and 98.9% of patients had a subjective cylinder ≤0.50 D and ≤1.00 D, respectively. Preoperative objective astigmatism measured with keratometry, autorefraction, and Scheimpflug tomography was significantly different (P < .05) from postoperative subjective refraction when all patients were analyzed; for patients with postoperative refractive astigmatism ≥0.50 D, preoperative astigmatism with keratometry and Scheimpflug tomography was not significantly different from postoperative refractive astigmatism. Preoperative objective astigmatism ≥0.50 D increased the risk ratio of postoperative subjective astigmatism ≥0.50 D by 2.2 (P < .001). CONCLUSIONS: Preoperative objective astigmatism could not be directly interchanged with postoperative subjective astigmatism, but the presence of preoperative astigmatism ≥0.50 D doubled the risk of inducing a postoperative subjective astigmatism ≥0.50 D. Extra care when performing subjective refraction should be taken in the presence of high objective astigmatism.

Comparison of efficacy and visual outcomes after SMILE and FS-LASIK for the correction of high myopia with the sum of myopia and astigmatism from -10.00 to -14.00 dioptres.

PURPOSE: To compare the efficacy and visual outcomes after femtosecond laser small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) in correcting high myopia. METHODS: This prospective, randomized study included patients who underwent SMILE or FS-LASIK for the correction of high myopia [the sum of spherical and cylindrical error from -10.00 to -14.00 dioptres (D)]. Preoperative, 1-month (P1m), 3-months (P3m) and 6-months (P6m) postoperative outcomes were analysed and compared between the two procedures. RESULTS: Ninety-six right eyes of 96 patients (SMILE: n = 51, FS-LASIK: n = 45) were included. Both the (Attempted - achieved) sphere and the (attempted - achieved) spherical equivalent (SEQ) were greater in the FS-LASIK group at all three postoperative time-points (p < 0.001). The postoperative vector means of astigmatism were smaller in the SMILE group than in the FS-LASIK group. The differences between the optical zone of tissue removal (ROZ) during surgery and the postoperative functional optical zone (FOZ; ROZ-FOZ) were smaller in the SMILE group than in the FS-LASIK group. No significant difference was found between the two procedures in the delta-root mean square (RMS) of aberrations, except for delta-spherical aberration (SA) at P3m. CONCLUSIONS: Both SMILE and FS-LASIK are effective in correcting high myopia. SMILE resulted in less under-correction, less regression, a smaller decrease in the FOZ and a smaller increase in SA when compared to FS-LASIK, resulting in better visual outcomes with SMILE.

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential.

The corneal stroma comprises 90% of the corneal thickness and is critical for the cornea's transparency and refractive function necessary for vision. When the corneal stroma is altered by disease, injury, or scarring, however, an irreversible loss of transparency can occur. Corneal stromal pathology is the cause of millions of cases of blindness globally, and although corneal transplantation is the standard therapy, a severe global deficit of donor corneal tissue and eye banking infrastructure exists, and is unable to meet the overwhelming need. An alternative approach is to harness the endogenous regenerative ability of the corneal stroma, which exhibits self-renewal of the collagenous extracellular matrix under appropriate conditions. To mimic endogenous stromal regeneration, however, is a challenge. Unlike the corneal epithelium and endothelium, the corneal stroma is an exquisitely organized extracellular matrix containing stromal cells, proteoglycans and corneal nerves that is difficult to recapitulate in vitro. Nevertheless, much progress has recently been made in developing stromal equivalents, and in this review the most recent approaches to stromal regeneration therapy are described and discussed. Novel approaches for stromal regeneration include human or animal corneal and/or non-corneal tissue that is acellular or is decellularized and/or re-cellularized, acellular bioengineered stromal scaffolds, tissue adhesives, 3D bioprinting and stromal stem cell therapy. This review highlights the techniques and advances that have achieved first clinical use or are close to translation for eventual therapeutic application in repairing and regenerating the corneal stroma, while the potential of these novel therapies for achieving effective stromal regeneration is discussed.

Biomechanical Changes after in vivo Enzyme-Induced Corneal Crosslinking in Rabbits.

INTRODUCTION: Enzyme-induced corneal crosslinking (CXL) may be a promising and effective method to stiffen the cornea. However, there have been no reports on the effect of corneal CXL with enzyme in vivo. OBJECTIVE: To evaluate the biomechanical efficacy after in vivo enzyme-induced corneal CXL in rabbits using noninvasive imaging. METHODS: The eyes of 10 white New Zealand rabbits were unilaterally treated with CXL enzyme (transglutaminases [Tgases]). The contralateral eyes served as negative controls. In every rabbit, a 1 U/mL solution of Tgases was applied to the corneal surface. Corneal dynamic deformation by an air puff was measured using high-speed Scheimpflug imaging on day 14 after the procedure. Biomechanical parameters, central corneal thickness, and intraocular pressure were recorded and assessed. Then, corneal buttons were excised from euthanized animals for hematoxylin and eosin staining to evaluate changes in corneal collagen distribution and cell damage. RESULTS: Some biomechanical parameters showed statistically significant changes after in vivo CXL. The deformation amplitude and maximum corneal velocity during the second applanations were significantly lower than those of the untreated control group. The second applanations were significantly increased compared to the control group. No changes were found in other parameters. The morphology of the corneal stroma was similar in CXL-treated and untreated corneas. No obvious cell apoptosis was observed. CONCLUSIONS: Corneal stiffness increased after in vivo CXL induced by Tgases. This CXL method may be useful for corneal ectasia.

Small incision lenticule extraction for the correction of high myopia.

PURPOSE: Excimer laser-based refractive procedures can have less predictable results when used for correcting high myopia than when used for moderate myopia. Small incision lenticule extraction might overcome this weakness. However, small incision lenticule extraction is only Food and Drug Administration approved for use in myopic eyes up to -8 D with astigmatism of -3 D or less. We report outcomes of small incision lenticule extraction in highly and moderately myopic eyes and compare these to modern laser-assisted in situ keratomileusis. METHODS: Retrospective, observational consecutive case series. Inclusion criteria: attempted myopic spherical correction ⩾-8 or-3 to -7.75 D with astigmatism ⩽-3 D, and corrected distance visual acuity of 1.0 (decimal scale) or better. RESULTS: A total of 62 highly myopic and 407 moderately myopic eyes were included. At 3 months postoperatively, the highly myopic eyes had a mean spherical equivalent refraction of -0.28 ± 0.41 D (range: -1.13 to +0.75 D). Mean uncorrected distance visual acuity was 1.0. Mean efficacy index was 0.84. Mean safety index was 1.03. Uncorrected distance visual acuity same or better than corrected distance visual acuity: 61%. Astigmatism was ⩽0.5 D in 90% and ⩽1 D in 100%. The results in the moderately myopic eyes were comparable. CONCLUSION: We found equally good visual and refractive outcomes after small incision lenticule extraction for the correction of high and of moderate myopia combined with an astigmatic correction of up to 3 D, respectively.

Corneal Cells: Fine-tuning Nerve Regeneration.

The cornea is a transparent outermost structure of the eye anterior segment comprising the highest density of innervated tissue. In the process of corneal innervation, trigeminal ganglion originated corneal nerves diligently traverse different corneal cell types in different corneal layers including the corneal stroma and epithelium. While crossing the stromal and epithelial cell layers during innervation, due to the existing physical contacts, close interactions occur between stromal keratocytes, epithelial cells, resident immune cells and corneal nerves. Furthermore, by producing various trophic and growth factors corneal cells assist in maintaining the growth and function of corneal nerves. Similarly, corneal nerve generated growth factors critically modify the corneal cell function in all the corneal layers. Due to their close association and contacts, on-going cross-communication between these cell types and corneal nerves play a vital role in the modulation of corneal nerve function, regeneration during wound healing. The present review highlights the influence of different corneal cell types and growth factors released from these cells on corneal nerve regeneration and function.