One-Year Follow-up of Corneal Confocal Microscopy After Corneal Cross-Linking in Patients With Post Laser In Situ Keratosmileusis Ectasia and Keratoconus

doi:10.1016/j.ajo.2008.11.017

American Journal of Ophthalmology

Volume 147, Issue 5, May 2009, Pages 774-778.e1

https://doi.org/10.1016/j.ajo.2008.11.017 Get rights and content

Purpose

To investigate corneal tissue alterations after corneal collagen cross-linking in patients with post laser in situ keratosmileusis (LASIK) keratectasia and keratoconus.

Design

Prospective comparative case series.

Methods

Five patients (5 eyes) with iatrogenic keratectasia after LASIK and 5 patients (5 eyes) with progressive keratoconus were included. All eyes underwent corneal cross-linking and were assessed by corneal in vivo confocal microscopy. Three normal/healthy and 3 post-LASIK without ectasia corneas were also examined as controls.

Results

All corneas revealed normal epithelial thickness before and after surgery. Images of both keratoconic and post-LASIK corneal ectasia eyes revealed similar morphologic alterations. The subepithelial nerve plexus was absent immediately after treatment; regeneration of nerves was evident after the third postoperative month. Keratocytes were absent from the anterior 300 μm of the stroma in the first 3 months while the posterior stromal density of keratocytes was increased. Corneal collagen fibers in the anterior stroma were distributed unevenly in a net-like formation. Full-thickness keratocyte repopulation in the anterior and mid-corneal stroma was detected 6 months after treatment. The corneal endothelium did not undergo any significant changes, since the cell density and hexagonality was not found altered during the follow-up period.

Conclusions

Keratocyte nuclei apoptosis in the anterior and intermediate corneal stroma along with collagen alterations were observed during the first 3 postcorneal cross-linking months. Gradual keratocyte repopulation was demonstrated over the following months. Corneal alterations after corneal cross-linking were similar in both keratoconic and post-LASIK corneal ectasia eyes.

Section snippets

Patient Population

This was a prospective study that included 10 eyes of 10 patients: 5 eyes with iatrogenic keratectasia after LASIK surgery and 5 eyes with progressive keratoconus. Three normal/healthy and 3 post-LASIK without ectasia corneas were also examined and were used as controls.

Corneal cross-linking treatment on the post-LASIK ectasia eyes was performed 20 to 36 months after LASIK. Exclusion criteria were corneal thickness less than 400 μm (minimum corneal pachymetry needed to perform corneal

Results

The preoperative confocal microscopy analysis of the eyes with post-LASIK corneal ectasia revealed unevenly distributed highly reflective collagen scars with reduced keratocyte density and background transparency at the anterior stroma when compared to either a normal cornea or a normal post-LASIK eye at the same stromal depth (FIGURE 1, FIGURE 2). These findings were limited at the area of the ectasia, while deeper stromal layers exhibited more normal keratocytes with signs of striae within

Discussion

Corneal cross-linking has been used as a treatment option in patients with either keratoconus or iatrogenic corneal ectasia after LASIK. The purpose of corneal cross-linking is to stabilize the corneal stroma and to delay the progression of these 2 pathologic entities. Studies on humans with keratoconus have demonstrated satisfactory short-term and long-term results with significant topographic and refractive improvement following treatment.⁷

Experimental studies on rabbit corneas have

George Kymionis, MD, PhD, is a clinical lecturer in University of Crete, Department of Ophthalmology. He completed his fellowship in refractive and corneal surgery at Bascom Palmer Eye Institute.

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Prospective Observational Study Evaluating Systemic Hormones and Corneal Crosslinking Effects in Keratoconus
2024, Ophthalmology Science
To evaluate associations between hormone levels and corneal parameters in patients with keratoconus (KC), before and after photooxidative corneal collagen crosslinking (CXL).
Prospective, observational cohort study.
Twenty-eight patients with KC who were scheduled for CXL at Aarhus University Hospital in Denmark.
Androgen (dehydroepiandrosterone sulfate [DHEA-S]) and estrogen (estrone and estriol) plasma levels were measured and clinical assessments were performed before CXL and 2 to 3 months post-CXL, comparing the CXL eye with the control eye from the same participant.
Associations between hormone levels and maximum corneal curvature (K_max) and minimum central corneal thickness (CCt_min) before and after CXL.
Corneal collagen crosslinking was associated with a 2% reduction in K_max values in the CXL eye, post-CXL, from baseline (median, 56.8 diopters [D]; 95% confidence interval [CI], 50.4–60.3) to the second visit (55.7 D; 95% CI, 50.4–58.8; P < 0.001). Systemic DHEA-S levels were 5 to 6 orders of magnitude higher than estriol or estrone concentrations in plasma. Importantly, estriol levels, rather than DHEA-S or estrone levels, were more closely correlated with K_max before CXL (Spearman’s r = 0.55, P = 0.01). Post-CXL K_max and CCt_min were not associated with DHEA-S, estrone, or estriol plasma levels at the same timepoint.
This study provides supporting evidence based on a KC clinical population that systemic estrogen levels may influence corneal parameters (curvature and thickness) pre-CXL. Further studies evaluating the interplay between the therapeutic benefits of CXL and systemic hormone distributions are needed to determine if perturbation of the local corneal microenvironment influences endocrine function.
The authors have no proprietary or commercial interest in any materials discussed in this article.
Effect of corneal stromal lenticule customization on neurite distribution and excitatory property
2022, Journal of Advanced Research
Refractive stromal lenticules from Small Incision Lenticule Extraction (SMILE), though usually discarded, hold a potential for various ophthalmic applications, including refractive correction, stromal volume expansion, and biomechanical strengthening of the cornea.
To investigate the effect of lenticule customization on lenticule neurite length profile and the excitatory response (calcium signaling) and the potential of reinnervation.
Human and porcine stromal lenticules were treated by (1) excimer laser reshaping, (2) ultraviolet A-riboflavin crosslinking (CXL), and (3) decellularization by sodium dodecyl sulfate (SDS), respectively. The overall neurite scaffold immuno-positive to TuJ1 (neuron-specific class III β-tubulin) expression and population of active neurite fragments with calcium response revealed by L-glutamate-induced Fluo-4-acetoxymethyl ester reaction were captured by wide-field laser-scanning confocal microscopy, followed by z-stack image construction. The NeuronJ plugin was used to measure neurite lengths for TuJ1 (NL-TuJ1) and calcium signal (NL-Ca). Reinnervation of lenticules was examined by the ex vivo grafting of chick dorsal root ganglia (DRG) to the decellularized human lenticules. Differences between groups and controls were analyzed with ANOVA and Mann-Whitney U test.
The customization methods significantly eliminated neurites inside the lenticules. NL-TuJ1 was significantly reduced by 84% after excimer laser reshaping, 54% after CXL, and 96% after decellularization. The neurite remnants from reshaping and CXL exhibited calcium signaling, indicative of residual excitatory response. Re-innervation occurred in the decellularized lenticules upon stimulation of the grafted chick embryo DRG with nerve growth factor (NGF 2.5S).
All of the lenticule customization procedures reduced lenticule neurites, but the residual neurites still showed excitatory potential. Even though these neurite remnants seemed minimal, they could be advantageous to reinnervation with axon growth and guidance after lenticule reimplantation for refractive and volume restoration of the cornea.
Late onset corneal haze after corneal cross-linking for progressive keratoconus
2019, American Journal of Ophthalmology Case Reports
To present the case of a patient that underwent corneal crosslinking for progressive keratoconus and 18 months later revealed clinically significant corneal stromal haze.
A 20-year-old male presented with progressive visual loss OU for the past few years. His corrected distance visual acuity (CDVA) OD was 20/30 (−2.75 -1.75 @55) and OS 20/30 (−0.50 -1.75@110). Corneal topography revealed keratoconus OU and the patient underwent corneal crosslinking according to the Dresden Protocol. The postoperative regimen included combined tobramycin and dexamethasone qid along with lubrication until epithelium healed and then fluorometholone qid with weekly tapering. At 3 months postoperatively, his topography was stable and his corrected distance visual acuity (CDVA) was 20/25 OU. On slit lamp examination, only clinically insignificant stromal haze was observed. At 18 months postoperatively, the patient reported vision deterioration. On examination his CDVA was 20/25 in right eye, and 20/40 in his left eye. Deep stromal haze was revealed in his central cornea, more dense in his left eye. Corneal topography was stable and the CDVA loss was attributed to the notable deep stromal haze. The patient was treated with dexamethasone qid with biweekly tapering. 18 months after corneal crosslinking, the patient demonstrated clinically significant stromal haze, most prominent OS. He was treated with dexamethasone qid. One month later his CDVA OS gradually improved to 20/25, and stromal haze was still noted but less dense.
Late-onset deep corneal haze is a possible complication of corneal crosslinking in keratoconic patients.
Three-Year Results of Simultaneous Transepithelial Phototherapeutic Keratectomy and Conventional Photorefractive Keratectomy (Cretan Protocol Plus) Followed by Corneal Crosslinking for Keratoconus
2023, Cornea
Management of Post-LASIK Ectasia
2023, Materia Socio-Medica
Novel Technique to Improve the Efficacy of Corneal Cross Linking in Cases of Post LASIK Ectasia
2023, Clinical Ophthalmology

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George Kymionis, MD, PhD, is a clinical lecturer in University of Crete, Department of Ophthalmology. He completed his fellowship in refractive and corneal surgery at Bascom Palmer Eye Institute.

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Original articleOne-Year Follow-up of Corneal Confocal Microscopy After Corneal Cross-Linking in Patients With Post Laser In Situ Keratosmileusis Ectasia and Keratoconus

Purpose

Design

Methods

Results

Conclusions

Section snippets

Patient Population

Results

Discussion

Surv Ophthalmol

J Cataract Refract Surg

J Cataract Refract Surg

Ophthalmology

Am J Ophthalmol

J Cataract Refract Surg

Ophthalmology

Keratoconus and corneal ectasia after LASIK

J Refract Surg

Current treatment options for corneal ectasia

Curr Opin Ophthalmol

Original article
One-Year Follow-up of Corneal Confocal Microscopy After Corneal Cross-Linking in Patients With Post Laser In Situ Keratosmileusis Ectasia and Keratoconus