Faculty Bibliography

We describe principles and initial clinical findings regarding a novel application of topographically customized collagen cross-linking (CXL) aiming to achieve a modest, nevertheless predictable hyperopic and presbyopic refractive changes. CXL is implemented in a specific, annular section mid-peripherally, employing differential response and biomechanical change, inducing central corneal steepening and asphericity changes. Efficacy, safety, and predictability of this procedure are also presented. This non-laser, minimally invasive technique may be applied either with epithelial removal, offering a more stable result or with a purely non-ablative and non-incisional approach, offering a minimally invasive alternative

PURPOSE: The aim of this study was to investigate the corneal thickness asymmetry indices in a large pool of patients with keratoconus derived using anterior segment optical coherence tomography (AS-OCT) in comparison with established Scheimpflug imaging-derived keratoconus classification indices. METHODS: Six specific indices were comparatively investigated in this study encompassing 2 groups: keratoconic group A (175 eyes) and age- and gender-matched control group B (175 eyes). AS-OCT was used for corneal focal thinning and irregularity indices, namely the superior nasal minus inferior temporal (SN-IT), superior minus inferior (S-I), minimum minus median (Min-Med) focal thinning, and thickness range, defined as the minimum minus maximum (Min-Max). Scheimpflug imaging was used for keratoconus grading and for investigating anterior surface irregularity index of height decentration (IHD) and index of surface variance (ISV). RESULTS: In study group A, SN-IT was 74.6 +/- 38.9 mum; S-I, 77.3 +/- 42.3 mum; Min-Med, -60.1 +/- 36.8 mum; and Min-Max, -117.7 +/- 55.4 mum. In control group B, SN-IT was 23.32 +/- 11.47 mum; S-I, 22.55 +/- 12.56 mum; Min-Med, -19.69 +/- 5.20 mum; and Min-Max, -55.24 +/- 12.96 mum. In group A, IHD was 0.077 +/- 0.055 and ISV was 84.24 +/- 48.61. In group B, IHD was 0.031 +/- 0.038 and ISV was 31.82 +/- 29.72. A statistically significant relationship was identified between SN-IT, S-I, Min-Med, and Min-Max indices with IHD and ISV (P < 0.01 in all pairs; coefficients of determination 0.649, 0.663, 0.481 and 0.483 versus IHD, and 0.690, 0.722, 0.551, and 0.562 versus ISV, respectively). CONCLUSIONS: This study presents a novel and comprehensive investigation of corneal asymmetry and focal thinning indices for keratoconus by AS-OCT. These indices correlate with established Scheimpflug-derived anterior surface irregularity indices, particularly in the early and milder stages. AS-OCT may hold promise as a helpful screening and diagnostic tool for suspect, early, and clinical keratoconus.

PURPOSE: To compare epithelial remodeling in keratoconic eyes that had photorefractive keratectomy and corneal collagen crosslinking (Athens protocol) with that in untreated keratoconic eyes and healthy eyes. SETTING: Private clinical practice, Athens, Greece. DESIGN: Comparative case series. METHODS: Fourier-domain anterior segment optical coherence tomography (AS-OCT) was used to obtain in vivo 3-dimensional epithelial thickness maps and center, superior, inferior, maximum, minimum, mean, midperipheral, and variability data. RESULTS: Group A comprised 175 treated keratoconic eyes (Athens protocol); Group B, 193 untreated keratoconic eyes; and Group C, 160 healthy eyes. The 1-year mean center epithelial thickness in Group A was 47.78 mum +/- 7.36 (SD) (range 33 to 64 mum). At the first clinical visit, it was 52.09 +/- 6.80 mum (range 36 to 72 mum) in Group B and 52.54 +/- 3.23 mum (range 45 to 59 mum) in Group C. The mean thickness range in Group A at 1 year was -19.94 +/- 7.21 mum (range -6 to -34 mum). It was -21.83 +/- 12.07 mum (range -4 to -66 mum) in Group B and -6.86 +/- 3.33 mum (range -3 to -29 mum) in Group C. The mean topographic thickness variability in Group A at 1 year was 4.64 +/- 1.63 mum (range 1.6 to 8.1 mum) (P<.05). It was 5.77 +/- 3.39 mum (range 1.3 to 17.8 mum) in Group B and 1.59 +/- 0.79 mum (range 0.6 to 5.6 mum) in Group C. CONCLUSION: Anterior segment OCT indicated a thinner and more homogeneous remodeled epithelium in the keratoconic eyes treated using the Athens protocol. FINANCIAL DISCLOSURE: Dr. Kanellopoulos is a consultant to Alcon Surgical, Inc.; Wavelight Laser Technologie AG; Avedro, Inc.; and i-Optics Optikgerate GmbH. Dr. Asimellis has no financial or proprietary interest in any material or method mentioned.

PURPOSE: To determine 3-dimensional corneal pachymetry distribution characteristics in a large pool of healthy normal patients. SETTING: Private practice, Athens, Greece. DESIGN: Prospective case series. METHODS: Spectral-domain anterior segment optical coherence tomography (AS-OCT) was used for measurements of central (CCT) and minimum corneal thickness, thickness asymmetry indices for superonasal-inferotemporal (SN-IT) and superior-inferior (S-I), and focal thinning indices (Min-Med focal thinning, Min-Max thickness range). RESULTS: The study enrolled 561 eyes. The mean values were CCT, 537.17 mum +/- 30.99 (SD) (range 447.0 to 654.0 mum); minimum corneal thickness, 529.01 +/- 30.02 mum (range 435.0 to 644.0 mum); SN-IT, 26.32 +/- 15.06 mum (range -23.0 to 97.0 mum); S-I, 25.34 +/- 15.06 mum (range -36.0 to 93.0 mum); Min-Med, -20.70 +/- 5.99 mum (range -7.0 to -50.0 mum); Min-Max, -59.79 +/- 16.55 mum (range -156.0 to -23.0 mum). There were significant age-related differences; the mean SN-IT was 22.19 +/- 12.40 mum (range -6.0 to 63.0 mum) in the younger group and 30.44 +/- 15.07 mum (range -4.0 to 97.0 mum) in the older group (P=.002). The mean S-I was 21.47 +/- 12.92 mum (range -5.0 to 70.0 mum) and 29.76 +/- 16.27 mum (range -8.0 to 93.0 mum), respectively (P=.001). CONCLUSIONS: Corneal-thickness asymmetry distribution in a healthy eye population obtained by Fourier-domain AS-OCT showed increased asymmetry in the older group; the asymmetry was not sex dependent. These findings may provide a benchmark for future comparative studies. FINANCIAL DISCLOSURES: Dr. Kanellopoulos is a consultant to Alcon Laboratories, Inc., Allergan, Inc., Avedro, Inc., Keramed, Inc., and i-Optics. No other author has a financial or proprietary interest in any material or method mentioned.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of very high-fluence collagen crosslinking (CXL) as a means of achieving increased corneal rigidity and reduced enzymatic digestion in the vehicle cornea of Boston keratoprosthesis (KPro) type 1. METHODS: Eleven consecutive patients fitted with a KPro (5 with a previous repeat cornea graft failure, 4 with ocular cicatricial pemphigoid, and 2 with chemical burn) underwent donor vehicle cornea pretreatment with very high-fluence prophylactic CXL in a 2-step procedure. First, the donor cornea was crosslinked with an intrastromal riboflavin instillation through a femtosecond laser-created pocket. This was followed up with a superficial CXL treatment. On the completion of the CXL pretreatment, the cornea center was trephined with the femtosecond laser, and the KPro was fitted onto the crosslinked donor cornea. Visual acuity, corneal surface, and donor vehicle cornea stability were evaluated. Follow-up evaluations were conducted over the next 9 years with a mean of 7.5 years. RESULTS: Mean uncorrected visual acuity improved from light perception to 20/60. One patient required a follow-up surgery, because of significant melt in the host cornea. None of the eyes developed melts and/or infection, especially on the vehicle cornea on which the KPro was fitted. CONCLUSIONS: Pretreatment with intrastromal and superficial very high-fluence CXL in conjunction with Boston type 1 KPro seems to be a safe and effective adjunctive treatment for achieving increased vehicle donor cornea rigidity. Additionally, there is an increased resistance to enzymatic degradation. This application may serve to enhance the biomechanical stability and external disease resistance of the donor vehicle cornea in patients with advanced external disease.

PURPOSE/OBJECTIVE:To map corneal and epithelial layer thickness changes following cataract removal surgery employing a spectral-domain anterior-segment optical coherence tomography system. METHODS:Corneal and epithelial thickness three-dimensional profile distribution was clinically imaged preoperatively and up to 3 months postoperatively with anterior-segment optical coherence tomography in 116 consecutive cases. Descriptive statistics investigated central corneal thickness, minimum corneal thickness, and epithelial thickness at the central 2-mm area, the mean over the 6-mm area, and mid-peripherally at 5-mm ring. RESULTS:In comparison to preoperative, the center, mean, and mid-peripheral epithelial thickness at the first postoperative day increased by +2.84, +2.35, and +2.25 μm, respectively (P < .001, < .001, and = .0014). One week postoperatively, the epithelial thickness differences were -1.91, -2.62, and -2.76 μm, respectively (P < .001, < .001, and < .001). Four weeks postoperatively, the differences of -0.20, -0.59, and -0.66 μm for the center, mean, and mid-periphery were not statistically significant (P = .6449, .1512, and .11097). Three months postoperatively, the differences were -0.05, -0.28, and -0.09 μm, respectively (P = .8722, .2341, and .6431). CONCLUSIONS:Qualitative and quantitative assessment of epithelial remodeling following cataract removal indicated that the early (1 day and 1 week) corneal and epithelial thickness returned to the preoperative baseline 4 weeks postoperatively. This in vivo epithelial and corneal screening with optical coherence tomography can be valuable for the postoperative assessment and follow-up.

PURPOSE/OBJECTIVE:To investigate preoperative and postoperative anterior and posterior keratometry and simulated corneal astigmatism in keratoconic eyes treated with collagen cross-linking combined with anterior surface normalization by partial topography-guided excimer ablation (the Athens Protocol). METHODS:Anterior and posterior corneal keratometry were measured by Scheimpflug imaging for 267 untreated keratoconic eyes. Following treatment, they were assessed 1 year postoperatively. RESULTS:Before treatment, average anterior keratometric value was 47.06 ± 6.02 diopters (D) for flat and 51.24 ± 6.75 D for steep. The posterior keratometric values were -6.70 ± 0.99 D (flat) and -7.67 ± 1.15 D (steep). Anterior astigmatism was on average with-the-rule (-1.97 ± 6.21 D), whereas posterior astigmatism was against-the-rule (+0.53 ± 1.02 D). The posterior and anterior astigmatism were highly correlated (r(2) = 0.839). After treatment, anterior keratometric values were 43.97 ± 5.81 D (flat) and 46.55 ± 6.82 D (steep). Posterior keratometric values were -6.58 ± 1.05 D (flat) and -7.69 ± 1.22 D (steep). Anterior astigmatism was on average with-the-rule (-1.56 ± 3.80 D), whereas posterior astigmatism was against-the-rule (+0.45 ± 1.29 D). The statistically significant (P < .05) keratometric changes indicated anterior surface flattening -3.09 ± 2.67 D (flat) and -4.19 ± 2.96 D (steep). The posterior keratometric changes were not statistically significant (P > .05). CONCLUSIONS:Before treatment, there was a strong correlation between posterior and anterior corneal astigmatism. After treatment, statistically significant anterior keratometric values flattened. The posterior surface keratometric values did not demonstrate statistically significant postoperative change: there was minimal posterior change, despite the significant anterior surface normalization.

PURPOSE: The aim of this study was to evaluate the possible topographic epithelial profile thickness changes (remodeling) after high myopic femtosecond laser in situ keratomileusis (LASIK) with concurrent prophylactic high-fluence cross-linking (CXL) in comparison with standard femtosecond LASIK. METHODS: Preoperative and 6-month postoperative 3-dimensional epithelial thickness distribution maps were investigated through clinical spectral domain anterior-segment optical coherence tomography in 2 groups of femtosecond laser-assisted myopic LASIK cases. Group A represented 67 eyes treated additionally with concurrent prophylactic CXL (LASIK-Xtra); group B represented 72 eyes subjected to stand-alone femtosecond LASIK. Optical coherence tomography measurements of the epithelial thickness over the center 2-mm-diameter disk, mid-peripheral 5-mm rim, and overall (the entire 6-mm-diameter disc area) were investigated. RESULTS: The comparison of matched myopic correction subgroups indicated statistically significant differences in the epithelial thickness increase specifically between high myopia subgroups. For example, in group A (LASIK-Xtra), the mid-peripheral epithelial thickness increase was +3.79 and +3.95 mum for the "-8.00 to -9.00 diopter" and "-7.00 to -8.00 diopter" subgroups, which compare with increased thickness in group B (stand-alone LASIK), of +9.75 mum (P = 0.032) and +7.14 mum (P = 0.041), respectively, for the same subgroups. CONCLUSIONS: Application of prophylactic CXL concurrently with high myopic LASIK operation results in a statistically significant reduced epithelial increase in comparison with stand-alone LASIK. This comparison is observed between matched high myopic correction subgroups. This difference may correlate with higher regression rates and/or may depict increased biomechanical instability in stand-alone LASIK.

PURPOSE: To report a novel application of toric topographically customized transepithelial collagen cross-linking (CXL) aiming to achieve refractive astigmatic changes in a keratoconic cornea. METHODS: Specially formulated riboflavin transepithelial administration and delivery of high-fluence UVA in a topographically customized pattern was applied in an eye with progressive keratoconus. Visual acuity, cornea clarity, keratometry, topography, and pachymetry with a multitude of modalities, as well as endothelial cell counts were evaluated for >6 months. RESULTS: Uncorrected distance visual acuity changed from preoperative 20/40 to 20/25 at 6 months. A mean astigmatic reduction of 0.8 D, and significant cornea surface normalization was achieved 6 months postoperatively. There was some mild change in the epithelial distribution, with the treated area having a slight normalization in the average epithelial thickness. CONCLUSIONS: We introduce herein the novel application of a topographically customizable transepithelial CXL in progressive keratoconus in order to achieve an astigmatic refractive effect and ectasia stabilization. This novel technique offers a nonablative and nonincisional approach to treat irregular astigmatism in ectatic cornea with rapid visual rehabilitation.