Marcony R. Santhiago

Association between the percent tissue altered and post-laser in situ keratomileusis ectasia in eyes with normal preoperative topography.

PURPOSE To investigate the association of a novel metric, percent tissue altered, with the occurrence of ectasia after laser in situ keratomileusis (LASIK) in eyes with normal corneal topography and to compare this metric with other recognized risk factors. DESIGN Retrospective case-control study. METHODS The study included 30 eyes from 16 patients with bilateral normal preoperative Placido-based corneal topography that developed ectasia after LASIK (ectasia group) and 174 eyes from 88 consecutive patients with uncomplicated LASIK and at least 3 years of postoperative follow-up. The following metrics were evaluated: age, preoperative central corneal thickness, residual stromal bed, Ectasia Risk Score System scores, and percent tissue altered, derived from [PTA = (FT + AD)/CCT], where FT = flap thickness, AD = ablation depth, and CCT = preoperative central corneal thickness. RESULTS In the ectasia group, percent tissue altered ≥40 was the most prevalent factor (97%), followed by age <30 years (63%), residual stromal bed ≤300 μm (57%), and ectasia risk score ≥ 3 (43%) (P < .001 for all). Percent tissue altered ≥ 40 had the highest odds ratio (223), followed by residual stromal bed ≤ 300 μm (74) and ectasia risk score ≥ 4 (8). Stepwise logistic regression revealed percent tissue altered ≥ 40 as the single most significant independent variable (P < .0001). CONCLUSIONS Percent tissue altered at the time of LASIK was significantly associated with the development of ectasia in eyes with normal preoperative topography and was a more robust indicator of risk than all other variables in this patient population.

Detection of Subclinical Keratoconus Using an Automated Decision Tree Classification

PURPOSE To develop a method for automatizing the detection of subclinical keratoconus based on a tree classification. DESIGN Retrospective case-control study. METHODS setting: University Hospital of Bordeaux. participants: A total of 372 eyes of 197 patients were enrolled: 177 normal eyes of 95 subjects, 47 eyes of 47 patients with forme fruste keratoconus, and 148 eyes of 102 patients with keratoconus. observation procedure: All eyes were imaged with a dual Scheimpflug analyzer. Fifty-five parameters derived from anterior and posterior corneal measurements were analyzed for each eye and a machine learning algorithm, the classification and regression tree, was used to classify the eyes into the 3 above-mentioned conditions. main outcome measures: The performance of the machine learning algorithm for classifying eye conditions was evaluated, and the curvature, elevation, pachymetric, and wavefront parameters were analyzed in each group and compared. RESULTS The discriminating rules generated with the automated decision tree classifier allowed for discrimination between normal and keratoconus with 100% sensitivity and 99.5% specificity, and between normal and forme fruste keratoconus with 93.6% sensitivity and 97.2% specificity. The algorithm selected as the most discriminant variables parameters related to posterior surface asymmetry and thickness spatial distribution. CONCLUSION The machine learning classifier showed very good performance for discriminating between normal corneas and forme fruste keratoconus and provided a tool that is closer to an automated medical reasoning. This might help in the surgical decision before refractive surgery by providing a good sensitivity in detecting ectasia-susceptible corneas.

Collagen crosslinking with riboflavin and ultraviolet-A in eyes with pseudophakic bullous keratopathy

PURPOSE: To evaluate the safety and efficacy of corneal collagen crosslinking (CXL) in patients with painful pseudophakic bullous keratopathy (PBK). SETTING: University of São Paulo, São Paulo and Sadalla Amin Ghanem Eye Hospital, Joinville, Santa Catarina, Brazil. METHODS: This prospective study included consecutive eyes with PBK that had CXL. After a 9.0 mm epithelial removal, riboflavin 0.1% with dextran 20% was applied for 30 minutes followed by ultraviolet‐A irradiation (370 nm, 3 mW/cm2). Therapeutic contact lenses were placed for 1 week. Corneal transparency, central corneal thickness (CCT), and ocular pain were assessed preoperatively and 1 and 6 months postoperatively. Statistical analysis was by paired t tests. RESULTS: Fourteen patients (14 eyes) with a mean age 71.14 years ± 11.70 (SD) (range 53 to 89 years) were enrolled. Corneal transparency was better in all eyes 1 month after surgery. At 6 months, corneal transparency was similar to preoperative levels (P = .218). The mean CCT was 747 μm preoperatively and 623 μm at 1 month; the decrease was statistically significant (P<.001). At 6 months, the mean CCT increased to 710 μm, still significantly thinner than preoperatively (P = .006). Pain scores at 6 months were not significantly different than preoperatively (P = .066). CONCLUSIONS: Corneal CXL significantly improved corneal transparency, corneal thickness, and ocular pain 1 month postoperatively. However, it did not seem to have a long‐lasting effect in decreasing pain and maintaining corneal transparency in patients with PBK. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Topographic, corneal wavefront, and refractive outcomes 2 years after collagen crosslinking for progressive keratoconus.

Purpose: The aim was to report the corneal higher-order aberrations (HOA), the topographic metrics, and the visual and refractive outcomes 2 years after performing collagen crosslinking (CXL) for progressive keratoconus. The correlation among corneal HOAs, topographic metrics, and visual acuity changes was also investigated. Methods: This is a prospective case series involving 42 eyes from 32 patients with progressive keratoconus treated with CXL. The main outcomes measured at baseline and 6, 12, and 24 months after treatment were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refractive changes, topographic data, and corneal aberrations. Results: Two years after CXL treatment, the UDVA (P < 0.001), CDVA (P < 0.001), and spherical equivalent (P = 0.048) improved significantly. The corneal topographic data revealed significant decreases in apical keratometry (P < 0.001), differential keratometry (P = 0.031), and central keratometry (P = 0.003) compared with the baseline measurements. Aberration analyses revealed a significant reduction in coma (P = 0.016), trefoil (P = 0.018), secondary astigmatism (P < 0.001), quatrefoil (P = 0.031), secondary coma (P < 0.001), and secondary trefoil (P = 0.001). Corneal HOA (except quatrefoil) demonstrated a significant correlation with postoperative CDVA; the highest correlations were for coma (rho = 0.703, P < 0.001), secondary astigmatism (rho = 0.519, P = 0.001), and total HOA (rho = 0.487, P = 0.001). However, the corneal HOA changes were not statistically associated with improved visual acuity. After treatment, the reduction in apical keratometry was the only variable that correlated with the improvement in the CDVA (rho = 0.319, P = 0.042). Conclusions: After 2 years, CXL was found to be effective in improving the UDVA, CDVA, topographic metrics, and most corneal HOAs in eyes with progressive keratoconus. A significant reduction was observed in apical keratometry, and this reduction directly correlated with an improvement in visual acuity.

Microkeratome versus femtosecond flaps: accuracy and complications.

Purpose of review To update the knowledge on differences between mechanical microkeratome and femtosecond flaps for laser in-situ keratomileusis (LASIK) in terms of accuracy and complications. Recent findings Corneal flaps created with the femtosecond laser present a more planar architecture and provide greater precision in flap diameter and thickness; a more uniform flap thickness across the flap diameter and it allows the surgeon to programme the angulation of the flap periphery. Femtosecond LASIK flaps are classically related to complications derived from a more intense inflammatory response, such as diffuse lamellar keratitis and transient light-sensitivity syndrome. Newer femtosecond models allow for much lower energy delivery to cut the flap, to the point the overall inflammatory response is not significantly different from the microkeratome. The incidence of complications such as epithelial defect and flap dislocations is higher with microkeratome flaps. Summary This review examines the accuracy and complications of flaps created with femtosecond and microkeratome. Both femtosecond and microkeratome are able to create accurate LASIK flaps. Femtosecond LASIK flaps represent significant improvement in morphology and predictability with implications for safety.

Biological and biomechanical responses to traditional epithelium-off and transepithelial riboflavin-UVA CXL techniques in rabbits.

PURPOSE To compare the biological effects of riboflavin-ultraviolet A (UVA) corneal cross-linking (CXL) performed with a traditional epithelium-off method to several transepithelial methods in a rabbit model. Preliminary experiments on biomechanical rigidity were also performed. METHODS Four treatment groups were included: (1) standard epithelium-off, (2) tetracaine transepithelial, (3) benzal-konium chloride-ethylenediaminetetraacetic acid (BKC-EDTA) transepithelial, and (4) femtosecond laser-assisted transepithelial riboflavin-UVA CXL. Six eyes from each treatment group and the untreated control group were analyzed at 24 hours and 2 months after treatment in wound healing studies. The TUNEL assay was performed to detect the extent of stromal cell death. Optical density was measured with a Scheimpflug analyzer. The corneal stiffening effect was quantitated in three eyes from each group using optical coherence elastography performed 2 months after treatments. RESULTS Twenty-four hours after CXL, stromal cell death extended full corneal thickness with both standard epithelium-off CXL and femtosecond laser-assisted CXL, but only approximately one-third stromal depth after BKC-EDTA transepithelial CXL. Negligible stromal cell death was detected with tetracaine transepithelial CXL. Cell death results were statistically different between the BKC-EDTA transepithelial CXL and standard epithelium-off CXL groups (P < .0001). Significant corneal opacity differences were noted. Standard epithelium-off CXL had the greatest density and tetracaine transepithelial CXL had the least density compared to the control group after treatment. As measured with optical coherence elastography, a trend toward greater mean stiffening was observed with BKC-EDTA transepithelial CXL than with epithelium-off CXL, femtosecond laser-assisted CXL, or tetracaine transepithelial CXL, but the result did not reach statistical significance. All of the CXL treatment groups exhibited significantly smaller variance of stiffness compared to the control group. CONCLUSION In the rabbit model, BKC-EDTA transepithelial CXL produced less stromal cell death and less risk of endothelial cell damage than standard epithelium-off CXL or femtosecond laser-assisted CXL. Additional study is needed to determine whether biomechanical stiffness is significantly different between the epithelium-off CXL and transepithelial CXL groups.

Effect of TGFβ and PDGF-B blockade on corneal myofibroblast development in mice

The purpose of this study was to investigate the role of transforming growth factor beta (TGFβ) and/or platelet-derived growth factor-B (PDGF-B) blockade on the differentiation of vimentin and alpha-smooth muscle actin (αSMA)-expressing myofibroblasts associated with haze in mice. Mouse corneas had haze-generating irregular PTK (phototherapeutic keratectomy) and topical treatment with the vectors. Six study groups of PTK treated corneas, with four corneas per group in each experiment, were Group 1) treated with TGFβ-KDEL vector interfering with TGFβ signaling through anomalous sorting of cytokine bound to the expressed altered receptor; Group 2) treated with PDGF-B-KDEL vector interfering with PDGF signaling through anomalous sorting of cytokine bound to the expressed altered receptor; Group 3) treated with both TGFβ-KDEL vector and PDGF-B-KDEL vector to interfere with signaling of both cytokines; Group 4) empty pGFPC1 vector; Group 5) empty pCMV vector; and Group 6) no vector treatment control. At one month after surgery, the corneas were analyzed by immunocytochemistry (IHC) for central stromal cells expressing myofibroblast markers vimentin and αSMA. The stroma of corneas treated with the TGFβ-KDEL vector alone (p < 0.05) or both the TGFβ-KDEL and PDGF-B-KDEL vectors (P < 0.05) had significantly lower density of vimentin-positive cells compared to the corresponding control group. The central stroma of corneas treated with the TGFβ-KDEL vector (p < 0.05) or the PDGF-B-KDEL vector (p < 0.05) had lower density of αSMA-positive cells compared to the corresponding control group. The density of αSMA-positive stromal cells was also significantly lower (p < 0.05) when both the TGFβ-KDEL and PDGF-B-KDEL and vectors were applied together compared to the corresponding control groups. This study provides in situ evidence that TGFβ and PDGF-B have important roles in modulating myofibroblast generation in the mouse cornea after haze-associated injury.

Transmission electron microscopy analysis of epithelial basement membrane repair in rabbit corneas with haze.

PURPOSE To assess the ultrastructure of the epithelial basement membrane using transmission electron microscopy (TEM) in rabbit corneas with and without subepithelial stroma opacity (haze). METHODS Two groups of eight rabbits each were included in this study. Photorefractive keratectomy (PRK) was performed using an excimer laser. The first group had -4.5-diopter (-4.5D) PRK and the second group had -9.0D PRK. Contralateral eyes were unwounded controls. Rabbits were sacrificed at 4 weeks after surgery. Immunohistochemical analysis was performed to detect the myofibroblast marker α-smooth muscle actin (SMA). TEM was performed to analyze the ultrastructure of the epithelial basement membrane and stroma. RESULTS At 4 weeks after PRK, α-SMA+ myofibroblasts were present at high density in the subepithelial stroma of rabbit eyes that had -9.0D PRK, along with prominent disorganized extracellular matrix, whereas few myofibroblasts and little disorganized extracellular matrix were noted in eyes that had -4.5D PRK. The epithelial basement membrane was irregular and discontinuous and lacking typical morphology in all corneas at 1 month after -9D PRK compared to corneas at 1 month in the -4.5D PRK group. CONCLUSIONS The epithelial basement membrane acts as a critical modulator of corneal wound healing. Structural and functional defects in the epithelial basement membrane correlate to both stromal myofibroblast development from precursor cells and continued myofibroblast viability, likely through the modulation of epithelial-stromal interactions mediated by cytokines. Prolonged stromal haze in the cornea is associated with abnormal regeneration of the epithelial basement membrane.

Peripheral sterile corneal ring infiltrate after riboflavin-UVA collagen cross-linking in keratoconus.

Purpose: To present 7 cases of peripheral sterile corneal infiltrates that occurred after corneal cross-linking (CXL) for progressive keratectasia. Methods: Seven patients who had their progressive keratoconus documented underwent corneal deepithelization and subsequently CXL, which was performed with the application of 0.1% riboflavin with 20% dextran, and exposure to UVA light (370 nm, 2.9–3.1 mW/cm2) for 30 minutes. Results: Nearly a week after the procedure, the patients presented with peripheral stromal infiltrates. The ring-like infiltrates were superficial and were present at the 9.0-mm zone. Sterile infiltration was diagnosed. Patients were treated with topical corticosteroids, and complete resolution was achieved after a few weeks of treatment. Conclusions: We hypothesize that the phototoxic effect on the corneal stroma may be the main mechanism that triggers these infiltrates. Alternatively, alterations in antigenicity that occur in native proteins after CXL could result in patients recognizing the proteins as nonself and mounting immune responses.

Ocular findings in patients with systemic sclerosis

OBJECTIVE: To evaluate the frequency and characteristics of ocular manifestations in outpatients with systemic sclerosis. METHODS: In this cross-sectional study, 45 patients with systemic sclerosis were enrolled. Data regarding demographics, disease duration and subtype, age at diagnosis, nailfold capillaroscopic pattern and autoantibody profile were collected, and a full ophthalmic examination was conducted. Parametric (Students t-test) and nonparametric (Mann-Whitney U test) tests were used to compare continuous variables. Fishers exact test was used to compare categorical data. P values < 0.05 were considered significant. RESULTS: Twenty-three subjects (51.1%) had eyelid skin changes; 22 (48.9%) had keratoconjunctivitis sicca, 19 (42.2%) had cataracts, 13 (28.9%) had retinal microvascular abnormalities and 6 (13.3%) had glaucoma. Eyelid skin changes were more frequent in patients with the diffuse subtype of systemic sclerosis and were associated with a younger age and an earlier age at diagnosis. Cataracts were presumed to be age-related and secondary to corticosteroid treatment. There was no association between demographic, clinical or serological data and keratoconjunctivitis sicca. The retinal microvascular abnormalities were indistinguishable from those related to systemic hypertension and were associated with an older age and a severe capillaroscopic pattern. CONCLUSIONS: Eyelid skin abnormalities and keratoconjunctivitis sicca were the most common ocular findings related to systemic sclerosis. Some demographic and clinical data were associated with some ophthalmic features and not with others, showing that the ocular manifestations of systemic sclerosis are characterized by heterogeneity and reflect the differences in the implicated pathophysiological mechanisms.