Marcella Q. Salomão

Femtosecond laser in laser in situ keratomileusis

Flap creation is a critical step in laser in situ keratomileusis (LASIK). Efforts to improve the safety and predictability of the lamellar incision have fostered the development of femtosecond lasers. Several advantages of the femtosecond laser over mechanical microkeratomes have been reported in LASIK surgery. In this article, we review common considerations in management and complications of this step in femtosecond laser-LASIK and concentrate primarily on the IntraLase laser because most published studies relate to this instrument.

Dry eye associated with laser in situ keratomileusis: Mechanical microkeratome versus femtosecond laser.

PURPOSE: To compare the incidence of laser in situ keratomileusis (LASIK)–associated dry eye and the need for postoperative cyclosporine A treatment after flap creation with a femtosecond laser and a mechanical microkeratome. SETTING: Cole Eye Institute, Cleveland, Ohio, USA. METHODS: Eyes were randomized to flap creation with an IntraLase femtosecond laser (30 or 60 kHz) or a Hansatome microkeratome. No patient had signs, symptoms, or treatment of dry eye preoperatively. Flap thickness was determined by intraoperative ultrasonic pachymetry. Slitlamp assessments of the cornea and need for postoperative dry‐eye treatment were evaluated preoperatively and 1 month postoperatively. RESULTS: The flap was created with the femtosecond laser in 113 eyes and with the microkeratome in 70 eyes. The difference in mean central flap thickness between the femtosecond group (111 μm ± 14 [SD]) and the microkeratome group (131 ± 25 μm) was statistically significant (P<.001). The incidence of LASIK‐associated dry eye was statistically significantly higher in the microkeratome group (46%) than in the femtosecond group (8%) (P<.0001), as was the need for postoperative cyclosporine A treatment (24% and 7%, respectively) (P<.01). In the microkeratome group, there was no correlation between thick flaps and a higher incidence of LASIK‐induced dry eye. CONCLUSIONS: Eyes with femtosecond flaps had a lower incidence of LASIK‐associated dry eye and required less treatment for the disorder. In addition to neurotrophic effects from corneal nerve cutting, other factors may be important because no correlation was found between flap thickness (or ablation depth) and the incidence of LASIK‐induced dry eye.

Discriminant Value of Custom Ocular Response Analyzer Waveform Derivatives in Keratoconus

PURPOSEnTo evaluate the performance of corneal hysteresis (CH), corneal resistance factor, and 16 investigator-derived Ocular Response Analyzer (ORA) variables in distinguishing keratoconus (KC) from the nondiseased state.nnnDESIGNnRetrospective case series.nnnPARTICIPANTSnFifty-four eyes of 27 unaffected patients and 49 eyes of 25 KC patients from the Instituto de Olhos, Rio de Janeiro, Brazil.nnnMETHODSnSixteen candidate variables were derived from exported ORA signals to characterize putative indicators of biomechanical behavior. Area under the receiver operating characteristic curve (AUC) and the Z statistic were used to compare diagnostic performance.nnnMAIN OUTCOME MEASURESnDiscriminant value of standard and derived ORA variables as measured by AUC.nnnRESULTSnFifteen of 16 candidate variables performed significantly better than chance (AUC, >0.5) at discriminating KC. Diagnostic performance was greatest for a custom variable related to the depth of deformation as defined by the minimum applanation signal intensity during corneal deformation (concavity(min); mean AUC ± standard error, 0.985 ± 0.002) and a new measure incorporating the pressure-deformation relationship of the entire response cycle (hysteresis loop area, 0.967 ± 0.002). Z statistics assessing the discriminative value of each of the top 5 variables demonstrated superiority to CH (AUC, 0.862 ± 0.002). Concavity(min) had the best overall predictive accuracy (cutoff value, 50.37; 94.9% sensitivity, 91.7% specificity, and 93.2% test accuracy), and the top 4 variables demonstrated the most consistent relationships to KC severity.nnnCONCLUSIONSnInvestigator-derived ORA variables related to the depth of deformation and the pressure-deformation relationship demonstrated very high test accuracy for detecting the presence of KC. Beyond their diagnostic value, the candidate variables described in this report provide mechanistic insight into the nature of the ORA signal and the characteristic changes in corneal dynamics associated with KC.

Corneal stroma PDGF blockade and myofibroblast development.

Myofibroblast development and haze generation in the corneal stroma is mediated by cytokines, including transforming growth factor-beta (TGF-beta), and possibly other cytokines. This study examined the effects of stromal PDGF-beta blockade on the development of myofibroblasts in response to -9.0 diopter photorefractive keratectomy in the rabbit. Rabbits that had haze generating photorefractive keratectomy (PRK, for 9 diopters of myopia) in one eye were divided into three different groups: stromal application of plasmid pCMV.PDGFRB.23KDEL expressing a subunit of PDGF receptor b (domains 2-3, which bind PDGF-B), stromal application of empty plasmid pCMV, or stromal application of balanced salt solution (BSS). The plasmids (at a concentration 1000ng/microl) or BSS was applied to the exposed stroma immediately after surgery and every 24h for 4-5 days until the epithelium healed. The group treated with pCMV.PDGFRB.23KDEL showed lower alphaSMA+ myofibroblast density in the anterior stroma compared to either control group (P<or=0.001). Although there was also lower corneal haze at the slit lamp at one month after surgery, the difference in haze after PDGF-B blockade was not statistically significant compared to either control group. Stromal PDGF-B blockade during the early postoperative period following PRK decreases stromal alphaSMA+ myofibroblast generation. PDGF is an important modulator of myofibroblast development in the cornea.

Corneal molecular and cellular biology update for the refractive surgeon

PURPOSEnTo review clinically relevant progress in understanding cellular and molecular interactions in the cornea that relate to refractive surgical outcomes in patients.nnnMETHODSnRecent published literature focused on femtosecond LASIK and surface ablation procedures, such as photorefractive keratectomy, was reviewed and correlated with clinical results of surgery.nnnRESULTSnThe femtosecond laser has a direct necrotic effect on stromal keratocytes, resulting in the release of cellular components that are chemotactic to bone marrow-derived inflammatory cells. Developments of the femtosecond laser led to lower energy delivery to the stroma and altered laser ablation profiles that decrease epithelial damage during the side-cut, and have markedly improved femtosecond LASIK to the point that the overall early postoperative healing response is indistinguishable from microkeratome LASIK. New studies have directly demonstrated the importance of surface irregularity and resulting structural and functional defects in the epithelial basement membrane, in the generation and persistence of anterior stromal myofibroblasts and haze following surface ablation procedures. These defects augment penetration of epithelium-derived TGF-beta, which is a critical modulator of myofibroblast development in the stroma. Studies on the mechanism of action of mitomycin C treatment to prevent haze have confirmed that the most powerful effect is on stromal cell proliferation and, therefore, decreased population of the anterior stroma with myofibroblast progenitor cells. An undesirable long-term effect of mitomycin C is diminished anterior stromal keratocyte density due to diminished keratocyte re-population. This raises concerns regarding future corneal anomalies in treated corneas.nnnCONCLUSIONSnBasic research studies of refractive procedures provide important insights into the effects of wound healing on surgical outcomes.

Corneal wound healing after ultraviolet-A/riboflavin collagen cross-linking: a rabbit study.

PURPOSEnTo investigate corneal wound healing following ultraviolet-A (UVA)/riboflavin corneal collagen cross-linking (CXL) in rabbit corneas.nnnMETHODSnThirty-six rabbits were enrolled in the study. Animals were divided into three treatment groups and corneas were analyzed at 24 hours and 4 weeks postoperatively. Thus, each group had 6 rabbits at each time point. Treatment groups were: 1) standard UVA+riboflavin CXL, 2) UVA alone, and 3) riboflavin alone. One eye of each rabbit served as an untreated control eye. TUNEL assay was performed to detect stromal cell apoptosis. Immunocytochemistry was performed to detect the inflammatory marker CD11b expressed in monocytes and the alpha-smooth muscle actin (SMA) marker expressed in myofibroblasts.nnnRESULTSnAt 24 hours, corneas from the UVA+riboflavin CXL group had significantly more apoptosis than the UVA alone and riboflavin alone groups. Eyes from all three groups had significantly more inflammatory cell influx into the cornea than unwounded controls. Four weeks after the procedure, many corneas in the UVA+riboflavin CXL group had mild haze, but very few SMA-positive myofibroblasts could be detected in the central cornea.nnnCONCLUSIONSnRiboflavin+UVA CXL triggers more anterior keratocyte apoptosis than corneal scrape with UVA alone or riboflavin alone. Inflammation monitored by the monocyte marker CD11b was present, but not statistically different among the three groups. Very little myofibroblast generation could be detected after UVA+riboflavin CXL, indicating that the mild stromal haze associated with this procedure is normally related to transient corneal fibroblast generation rather than more persistent haze due to generation of myofibroblasts.

Advances in anterior segment imaging and analysis.

Purpose of review Efforts to visualize and quantify key aspects of anterior segment ocular anatomy have fostered the development of many new imaging modalities and supportive technological advances in the last decade. This has been accompanied by an increase in the quantity and complexity of data available to the clinician. This article briefly reviews recent imaging advances and new challenges in the effective use of these complex datasets to solve clinical problems. Recent findings The current revolution in corneal imaging includes two advancing fronts: new or improved imaging modalities and new methods of data representation. Areas of significant activity include increased speed and resolution, enhanced microstructural imaging, and marked increases in the amount of data available on the three-dimensional macrostructure and microstructure of the cornea. Some efforts to represent these data in clinically useful terms and to emphasize critical interpretation of the end-user data are reviewed. Summary Recent advances in anterior segment imaging technology bring new opportunities and novel challenges to the end-user. These developments are capable of producing increasingly sophisticated three-dimensional representations of the anterior segment that will support novel applications for the diagnosis and treatment of anterior segment disease.