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Anastasios John Kanellopoulos,1,2,* Matthias Maus,3,* Chandra Bala,4,* Cody Hamilton,5,* Sissimos Lemonis,6,* Maria Elena Jockovich,5,* Ramin Khoramnia7,* 1LaserVision Ambulatory Surgical Unit, Athens, Greece; 2Department of Ophthalmology, NYU Grossman School of Medicine, New York City, NY, USA; 3Sehkraft Augenzentrum, Köln, Germany; 4PersonalEyes, Sydney, NSW, Australia; 5Alcon Vision, LLC, Fort Worth, TX, USA; 6Alcon Deutschland GmbH, Freiburg, Germany; 7Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany*These authors contributed equally to this workCorrespondence: Anastasios John Kanellopoulos, LaserVision Ambulatory Surgical Unit, An Thocha 17, Athens, 11521, Greece, Tel +302107472777, Fax + 302107472789, Email ajkmd@mac.com

Anastasios John Kanellopoulos1,2 1Medical Director: The Laservision Clinical and Research Institute, Athens, Greece; 2Clinical Professor, Department of Ophthalmology, NYU Grossman Medical School, Department of Ophthalmology, New York City, NY, USACorrespondence: Anastasios John Kanellopoulos, Clinical Professor of Ophthalmology, NYU Medical School, Medical Director: The Laservision Clinical and Research Institute, 17 Tsocha Street, Athens, 115 21, Greece, Tel + 30 210 7472777, Fax + 30 210 7472789, Email ajkmd@mac.comPurpose: The safety and long-term efficacy of automated ray-tracing customized myopic and myopic astigmatic femtosecond laser-assisted LASIK.Methods: This consecutive case series retrospective analysis, of 20 subjects (40 eyes) treated with automated raytracing named Wavelight Plus, to include low and high order aberrations based on a three-dimensional custom virtual eye for each case-calculated from interferometry data-obtained from a single diagnostic device that also provides Hartman–Shack Wavefront and Scheimpflug tomography data. We evaluated before and after the customized LASIK procedure: visual acuity, refractive error, high order aberrations, contrast sensitivity, and psychometric post-operative visual function data.Results: At 24 months, the comparison of the pre-operative to the post-operative refractive and visual function value changes in average were: subjective manifest refraction from − 4.38 ± 2.54 diopters (D) (range − 9.75 to − 1.25 D) to +0.11 ± 0.19 D; subjective manifest refractive astigmatism from − 0.76 ± 0.91 D (range − 2.75 to 0 D) to − 0.13 ± 0.16 D, corneal astigmatism from − 1.16 ± 0.64 D (range − 0.2 to − 2.8) to − 0.47 ± 0.11 D. 65% of the eyes studied demonstrated an increase of at least one line of vision, while from the same group 38% demonstrated 2 lines of increase. High order aberrations, contrast sensitivity as well as the subjective psychometric input based on the VFQ-25 questionnaire demonstrated actual improvement.Conclusion: This longer-term follow-up, single-arm retrospective consecutive case series documents LASIK treatment customization that appears to be safe and effective in the correction of myopia and myopic astigmatism. Markedly improved objective and subjective visual function post-operatively, underlying the potential importance of simultaneously attempting to correct high order aberrations and improving the spatial alignment of total, measured human eye optics.Keywords: raytracing excimer customization of myopic corrections, topography-guided, wavefront-guided, femtosecond-laser assisted myopic LASIK, customized excimer laser ablation: human eye optical tilt between the cornea and the crystalline lens

Anastasios John Kanellopoulos,1,2,* Matthias Maus,3,* Chandra Bala,4,* Cody Hamilton,5,* Sissimos Lemonis,6,* Maria Elena Jockovich,5,* Ramin Khoramnia7,* 1LaserVision Ambulatory Surgical Unit, Athens, Greece; 2Department of Ophthalmology, NYU Grossman School of Medicine, New York City, NY, USA; 3Sehkraft Augenzentrum, Köln, Germany; 4PersonalEyes, Sydney, NSW, Australia; 5Alcon Vision, LLC, Fort Worth, TX, USA; 6Alcon Deutschland GmbH, Freiburg, Germany; 7Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany*These authors contributed equally to this workCorrespondence: Anastasios John Kanellopoulos, LaserVision Ambulatory Surgical Unit, An Thocha 17, Athens, 115 21, Greece, Tel +30 (210) 7472777, Fax + 30 (210) 7472789, Email ajkmd@mac.comPurpose: To assess the safety and efficacy of a customized ablation treatment (InnovEyes) to correct myopia and myopic astigmatism with femtosecond laser-assisted in situ keratomileusis (Femto LASIK).Patients and Methods: In this prospective, nonrandomized, multicenter study, 113 patients (225 eyes) with preoperative myopia less than − 9.0 diopters (D) and astigmatism 0 to − 4.0 D (based on InnovEyes refraction) underwent wavefront, tomography, and biometry assessment using a single diagnostic device (InnovEyes sightmap). These data were imported and used unmodified by the InnovEyes algorithm to automatically calculate and optimize correction of lower- and higher‑order aberrations (HOAs) treated by the EX500 ablation profile. Visual acuity, refractive error, HOAs, and patient satisfaction were evaluated over 3 months.Results: A total of 106 patients (212 eyes) completed the study and were included in the analysis. Mean preoperative manifest refraction spherical equivalent (MRSE) was − 3.38± 1.76 D. At Month 3, uncorrected distance visual acuity was 20/20 or better in 208/212 (98.1%) eyes, and it was the same as, or better than, the preoperative best-corrected distance visual acuity (CDVA) in 162/212 (76.4%) eyes; 76/212 (35.8%) eyes gained ≥ 1 line of CDVA. MRSE was within ± 0.5 D in 195/212 (92.0%) eyes. Additionally, 201/209 (96.2%) eyes had no change (defined as a change between − 0.1 μm and 0.1 μm, inclusive) in HOAs, and 105/106 (99.1%) patients reported to be satisfied with the results.Conclusion: Customizing ray-tracing Femto LASIK with this platform appeared safe and effective in correcting myopic astigmatism and also achieved a significant percentage of eyes gaining lines of vision, potentially by addressing HOAs, along with a consistently high level of patient satisfaction.Keywords: myopic astigmatism, higher-order aberrations, manifest refraction spherical equivalent, corrected distance visual acuity

Anastasios John Kanellopoulos1,2 1Laservision.gr Clinical and Research Institute, Athens, Greece; 2NYU Medical School, Department of Ophthalmology, New York City, NY, USACorrespondence: Anastasios John KanellopoulosLaservision.gr Clinical and Research Institute, 17 Tsocha Street, Athens 115 21, GreeceTel + 30 210 7472777Fax + 30 210 7472789Email ajkmd@mac.comPurpose: Safety and efficacy of a novel automated ray tracing optimization in customization of excimer ablation in myopic LASIK.Methods: In a consecutive case series, 25 patients (50 eyes) undergoing femtosecond-laser-assisted myopic LASIK were evaluated. The novel, artificial-intelligence platform initially calculates the ablation profile based on a model eye for each case, based on interferometry axial length data. Low- and high-order aberration calculation is performed by raytracing based on wavefront and Scheimpflug tomography measurements, all from a single diagnostic device. Visual acuity, refractive error, keratometry, topography, high-order aberrations and contrast sensitivity were evaluated, over six months follow-up.Results: Change from pre- to 6 months post-operative: mean refractive error improved from − 5.06 ± 2.54 diopters (D) (range − 8.0 to − 0.50 D) to − 0.11 ± 0.09 D (range − 0.25 to + 0.25); refractive astigmatism from − 1.07 ± 0.91 D (range − 4.25 to 0 D) to − 0.15 ± 0.04 D (range − 0.25 to 0); and topographic astigmatism from − 1.65 ± 0.85 D to − 0.26 ± 0.11 D (range − 0.60 to 0). About 65% of eyes gained one line of vision and 38% 2 lines. Pre- to post-operative high-order aberration average: RMSh changed from 0.25 um to 0.35 um. Contrast sensitivity improved post-operatively.Conclusion: We report safe and effective preliminary outcomes with a novel excimer laser customization by ray tracing optimization, for myopic LASIK treatments, employing several independent up-till-now diagnostics and a customized eye model reference for each case. It bears the potential advantage through total eye aberration data and ray tracing refraction calculation to offer improved and more predictable visual outcomes.Keywords: ray tracing excimer customization, topography-guided, wavefront-guided, femtosecond-laser assisted myopic LASIK, customized excimer ablation

Anastasios John Kanellopoulos1,2 1Department of Ophthalmology, The LaserVision Clinical and Research Eye Institute, Athens, Attiki, Greece; 2Department of Ophthalmology, New York University Medical School, New York City, NY, USACorrespondence: Anastasios John KanellopoulosThe LaserVision Clinical and Research Eye Institute, Athens, GreeceTel + 30 210 7472777Fax + 30 210 7472789Email ajkmd@mac.comPurpose: To evaluate and compare the repeatability and agreement of Scheimpflug vs scanning-slit tomography of the cornea and the anterior chamber in terms of keratometric and tomographic indices in healthy eyes.Methods: The 20 eyes of 10 healthy participants underwent 3 consecutive measurements using both Scheimpflug-tomography and scanning-slit tomography, diagnostic devices. Multiple corneal and anterior chamber tomographic parameters were recorded and evaluated to include corneal keratometry and its axis; corneal best-fit sphere (BFS), pachymetry mapping, angle kappa, anterior chamber depth (ACD), pupil diameter, and location. Repeatability for each device was assessed using the within each subject standard deviation of sequential exams, the coefficient variation (CV) and the intraclass correlation coefficient (ICC). Agreement between the two devices was assessed using Bland–Altman plots with 95% limits of agreement (LoA) and correlation coefficient (r).Results: Both devices were found to have high repeatability (ICC> 0.9) both in keratometric and other tomographic measurements. Scheimpflug tomography’s repeatability though appeared superior in the average keratometry values, anterior and posterior BFS, thinnest corneal pachymetry value and location (p< 0.05). Agreement: Statistically significant inter-device differences were noted in the mean values of K1, K2, BFS, ACD and thinnest corneal pachymetry (p< 0.05). Despite the agreement differences noted, the two devices were well correlated (r> 0.8) in respective measurements with Scheimpflug delivering consistently lower values than the scanning-slit tomography device.Conclusion: Scheimpflug-tomography repeatability was found to be superior to that of scanning-slit tomography in this specific study, in most parameters evaluated. Inter-device agreement evaluation suggests that reading from the two devices may not be used interchangeably in absolute values, yet they are well correlated with Scheimpflug delivering consistently lower values in most.Keywords: Pentacam, Orbscan, Scheimpflug corneal tomography, scanning-slit corneal tomography

Anastasios John Kanellopoulos,1,2 Filippos Vingopoulos1 1Department of Ophthalmology, LaserVision Clinical & Research Eye Institute, Athens, Greece; 2Department of Ophthalmology, New York University Medical School, New York, NY, USACorrespondence: Anastasios John KanellopoulosLaserVision Clinical & Research Eye Institute, Tsocha str. 15 - 17, Athens 115 21, GreeceTel + 30 210 7472777Email ajkmd@mac.comPurpose: The ex-vivo feasibility of creating corneal ring segments (ICRS) from biological tissue (xenograft porcine cornea) and combining intra-corneal implantation with Corneal CrossLinking (CXL).Methods: The ring segments from gamma-irradiated porcine donor cornea were shaped and implanted in human cadaver host cornea using a femtosecond laser for their dissection and host cornea channel preparation. Intra-channel 0.25% riboflavin solution combined with higher fluence CXL of 15 joules total energy followed their implantation. Anterior segment Optical Coherence Tomography (OCT), Scheimpflug tomography and Placido-disc topography were used to monitor the positioning and refractive effect.Results: The novel xenograft ring segments were positioned as planned at 85% corneal depth and mid-peripheral, with documented, up to 7 diopters central cornea flattening.Conclusion: Xenograft intracorneal ring segments combined with CXL may offer an alternative to the synthetic materials used clinically so far, aiming in reducing complications of intracorneal opaque deposit accumulation, segment migration, corneal erosion and potential extrusion. Combining CXL may enhance their refractive effect and stabilize potential or documented host ectasia.Keywords: intrastromal corneal ring segments, gamma-radiated porcine cornea, biological tissue, xenograft corneal surgery, myopia correction, cornea transplantation

Anastasios John Kanellopoulos1,2 1Department of Ophthalmology, Laservision.gr, Clinical and Research Eye Institute, Athens, Greece; 2NYU Medical School, Department of Ophthalmology, New York, NY, USA Purpose: The aim of this study was to evaluate the health-related quality of life (HRQoL) before and after the management of keratoconus (KCN) with Combined Topography-Guided Transepithelial partial photorefractive keratectomy (PRK) and corneal Cross-Linking: the Athens Protocol.Patients and methods: Thirty-four consecutive patients treated for progressive KCN were selected for retrospective telephone interview and individual questionnaire submission. A disease-specific HRQoL questionnaire was administered before and after the Athens Protocol intervention, using the following administrative questionnaires: National Eye Institute Visual Function Questionnaire (NEI VFQ) 25/39 and IVI-28. The disease grade was ranked according to the Amsler–Krumeich classification (KCN severity). Reliability of collected data was evaluated with Cronbach’s α test.Results: Patients’ age ranged from 15 to 51 years at the time of the operation. Mean time before the operation during which the questionnaires were administered was 52±6 months. General visual acuity, psychological well-being, and driving ability showed significant improvement. Younger keratoconic patients tend to have more enhanced psychological status and to cope better with difficulties in everyday activities (prior to operation) than older patients.Conclusion: The Athens Protocol treatment has been proven to be beneficial to patients in a large number of aspects. Keywords: KCN, Athens Protocol, topography-guided PRK, quality of life, HRQoL questionnaire, NEI VFQ, IVI-28

Anastasios John Kanellopoulos1,2 1Department of Ophthalmology, LaserVision Clinical and Research Institute, Athens, Greece; 2Department of Ophthalmology, NYU Medical School, New York, NY, USA Purpose: To report a novel application of partial topography-guided photorefractive keratectomy combined with topographically customized, higher fluence, and variable pattern corneal cross-linking applied on the same day of the treatment of keratoconus. Methods: A topography-guided partial photorefractive keratectomy treatment of maximum 30 mm over the thinnest cone area was applied initially followed by a 7 mm, 50 mm phototherapeutic keratectomy treatment to address epithelial removal. 0.02% Mitomycin C was applied for 20 seconds and then the exposed stroma was soaked with 0.1% riboflavin solution for 5 minutes. The cornea was then treated with a customized, variable-pattern and 20 mW/cm2 fluence for a total of 5–10 J, and up to 15 J of energy was delivered with the KXL-II device employing an active tracker. The center of the pattern that received the 15 J was topography-matched with the thinnest area of the cone. Visual acuity, refractive error, cornea clarity, keratometry, topography, pachymetry with a multitude of modalities and endothelial cell density were evaluated over 36 months. Results: Keratoconus was stabilized in all cases. The severity of keratoconus stage by Amsler–Krumeich criteria improved from an average of 3.2 (1–4) to 1.8 (0–3). Uncorrected distance visual acuity changed from preoperative 20/80 to 20/25 at 6 months. A maximum astigmatic reduction of 7.8 D (5.3–15.6), and a significant cornea surface normalization (an index of height decentration improvement from 0.155 [±0.065] to 0.045 [±0.042]) were achieved by 1 month and remained relatively stable for 36 months postoperatively. Two cases delayed full reepithelialization for up to 9 days. Conclusion: This paper introduces a novel technique in order to maximize the refractive normalization effect along with ectasia stabilization in young keratoconus patients. This may facilitate the use of less tissue ablation, in comparison to utilizing a homogeneous UV light beam for corneal cross-linking in Athens Protocol cases. It broadens the number of potential candidate cases that would have been limited to employ this technique due to tissue thickness limitations. Keywords: corneal ectasia, corneal irregularity-normalization, therapeutic excimer ablation

Anastasios John Kanellopoulos1,2 1Department of Ophthalmology, Laservision Clinical and Research Institute, Athens, Greece; 2Department of Ophthalmology, New York University Medical School, New York, NY, USA Purpose: To investigate ex vivo potentially different corneal biomechanical properties after small-incision lenticule extraction (SMILE) versus LASIK for myopic correction.Methods: Thirty human donor corneas were subjected to either myopic SMILE or femtosecond laser-assisted LASIK. Donor corneas were assigned to six investigative groups: Group A, –3.00 D (diopters) SMILE; Group B, –8.00 D SMILE; Group C, –3.00 D LASIK; and Group D, –8.00 D LASIK. Additionally, two control groups were formed: Group E, SMILE and Group F, LASIK. All groups consisted of five corneas, randomly allocated. The corneas in the control groups were subjected to the corresponding femtosecond-laser lamellar cuts but not to tissue removal. Evaluation of biomechanical tensile strength was conducted by biaxial force application. Primary outcome measures were stress at 10% and 15% strain, and Young’s modulus at 10% and 15% strain.Results: In SMILE, the average relative difference (Δ) of the four outcome measures was –34.46% for –3.00 D correction versus control Group E and –49.34% for –8.00 D correction versus control Group E. In LASIK, average Δ was –24.88% for –3.00 D correction versus control, and –52.73% for –8.00 D correction versus control. All these differences were statistically significant; SMILE compared to LASIK for the same myopic correction appears to result in more biomechanical reduction for –3.00 D corrections by –26%, while a nonstatistically significant difference was noted in –8.00 D corrections.Conclusion: Both SMILE and LASIK procedures do substantially alter corneal biomechanical properties, and the degree of tensile strength reduction is statistically significantly correlated to the extent of myopic correction. Additionally, SMILE procedure seems to result in more tensile strength reduction in lower myopic corrections compared to LASIK, and similar tensile strength reduction to LASIK in higher myopic corrections when compared to LASIK. Keywords: SMILE, femto-second LASIK, myopic LASIK, corneal biomechanics, Young’s modulus, corneal stress–strain, shear strength, tensile strength

Anastasios John Kanellopoulos1,2 1LaserVision Clinical and Research Institute, Athens, Greece; 2Department of Ophthalmology, NYU Medical School, New York, NY, USA Purpose: To evaluate the safety, efficacy, and contralateral eye comparison of topography-guided myopic LASIK with two different refraction treatment strategies. Setting: Private clinical ophthalmology practice. Patients and methods: A total of 100 eyes (50 patients) in consecutive cases of myopic topography-guided LASIK procedures with the same refractive platform (FS200 femtosecond and EX500 excimer lasers) were randomized for treatment as follows: one eye with the standard clinical refraction (group A) and the contralateral eye with the topographic astigmatic power and axis (topography-modified treatment refraction; group B). All cases were evaluated pre- and post-operatively for the following parameters: refractive error, best corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), topography (Placido-disk based) and tomography (Scheimpflug-image based), wavefront analysis, pupillometry, and contrast sensitivity. Follow-up visits were conducted for at least 12 months. Results: Mean refractive error was -5.5 D of myopia and -1.75 D of astigmatism. In group A versus group B, respectively, the average UDVA improved from 20/200 to 20/20 versus 20/16; post-operative CDVA was 20/20 and 20/13.5; 1 line of vision gained was 27.8% and 55.6%; and 2 lines of vision gained was 5.6% and 11.1%. In group A, 27.8% of eyes had over -0.50 diopters of residual refractive astigmatism, in comparison to 11.7% in group B (P

Anastasios John Kanellopoulos,1,2 George Asimellis11LaserVision.gr Clinical and Research Eye Institute, Athens, Greece; 2New York University Medical School, New York, NY, USAPurpose: To investigate repeatability of steep and flat keratometry measurements, as well as astigmatism axis in cohorts with normal range and regular astigmatic such as: eyes following laser-assisted in situ keratomileusis (LASIK) and normal population, as well as cohorts of high and irregular astigmatism such as keratoconic eyes, and keratoconic eyes following corneal collagen cross-linking, employing a novel corneal reflection topography device.Methods: Steep and flat keratometry and astigmatism axis measurement repeatability was investigated employing a novel multicolored-spot reflection topographer (Cassini) in four study groups, namely a post myopic LASIK-treated Group A, a keratoconus Group B, a post-CXL keratoconus Group C, and a control Group D of routine healthy patients. Three separate, maps were obtained employing the Cassini, enabling investigation of the intra-individual repeatability by standard deviation. Additionally we investigated in all groups,the Klyce surface irregularity indices for keratoconus, the SAI (surface asymmetry index) and the SRI (surface regularity index).Results: Flat keratometry repeatability was 0.74±0.89 (0.03 to 5.26) diopters (D) in the LASIK Group A, 0.88±1.45 (range minimum to maximum, 0.00 to 7.84) D in the keratoconic Group B, and 0.71±0.94 (0.02 to 6.23) D in the cross-linked Group C. The control Group D had flat keratometry repeatability 0.36±0.46 (0.00 to 2.71) D. Steep keratometry repeatability was 0.64±0.82 (0.01 to 4.81) D in the LASIK Group A, 0.89±1.22 (0.02 to 7.85) D in the keratoconic Group B, and 0.93±1.12 (0.04 to 5.93) D in the cross-linked Group C. The control Group D had steep keratometry repeatability 0.41±0.50 (0.00 to 3.51) D. Axis repeatability was 3.45±1.62° (0.38 to 7.78°) for the LASIK Group A, 4.12±3.17° (0.02 to 12.13°) for the keratoconic Group B, and 3.20±1.99° (0.17 to 8.61°) for the cross-linked Group C. The control Group D had axis repeatability 2.16±1.39° (0.05 to 5.86°). The SAI index measurement repeatability was 0.33±0.40 (0.01 to 2.31) in the post-LASIK Group A, 0.39±0.75 (0.00 to 7.15) in the keratoconic Group B, and 0.43±0.56 (0.05 to 3.50) in the keratoconus post-CXL Group C. The control group had SAI measurement repeatability of 0.26±0.30 (0.00 to 2.39). The SRI index repeatability was 0.22±0.17 (0.01 to 0.96) for post-LASIK Group A, 0.20±0.18 (0.00 to 1.07) in keratoconic Group B, and 0.13±0.09 (0.00 to 0.45) in the keratoconus post-CXL Group C. The control Group D had SRI measurement repeatability of 0.23±0.16 (0.00 to 0.75).Conclusion: This novel corneal topography device appears to offer very high specificity in estimating corneal keratometry and specific corneal irregularity indices, even in topographically challenging corneas such as LASIK treated, keratoconic, and cross-linked.Keywords: LED topography, point-source topography, VU topographer, axis of astigmatism, Cassini topographer, steep meridian, surface regularity index, surface asymmetry index, form factor

Anastasios John Kanellopoulos,1,2 George Asimellis1 1LaserViison.gr Clinical and Research Eye Institute, Athens, Greece; 2Department of Ophthalmology, New York University Medical School, New York, NY, USAPurpose: To report novel application of topographically-customized collagen crosslinking aiming to achieve hyperopic refractive changes. Two approaches were evaluated, one based on epithelium-off and one based on epithelium-on (transepithelial). Methods: A peripheral annular-shaped topographically customizable design was employed for high-fluence ultraviolet (UV)-A irradiation aiming to achieve hyperopic refractive changes. A total of ten eyes were involved in this study. In group-A (five eyes), a customizable ring pattern was employed to debride the epithelium by excimer laser ablation, while in group-B (also five eyes), the epithelium remained intact. In both groups, specially formulated riboflavin solutions were applied. Visual acuity, cornea clarity, keratometry, topography, and pachymetry with a multitude of modalities, as well as endothelial cell counts were evaluated. Results: One year postoperatively, the following changes have been noted: in group-A, average uncorrected distance visual acuity changed from 20/63 to 20/40. A mean hyperopic refractive increase of +0.75 D was achieved. There was some mild reduction in the epithelial thickness. In group-B, average uncorrected distance visual acuity changed from 20/70 to 20/50. A mean hyperopic refractive increase of +0.85 D was achieved. Epithelial thickness returned to slightly reduced levels (compared to baseline) in group-A, whereas to slightly increased levels in group-B. Conclusion: We introduce herein the novel application of a topographically-customizable collagen crosslinking to achieve a hyperopic refractive effect. This novel technique may be applied either with epithelial removal, offering a more stable result or with a non-ablative and non-incisional approach, offering a minimally invasive alternative.Keywords: topography customizable crosslinking, high-fluence cross linking, epi-on and epi-off CXL, PiXL, KXL II, CXL hyperopic correction, CXL presbyopic correction

Anastasios John Kanellopoulos,1,2 George Asimellis1 1LaserVision.gr Eye Institute, Athens, Greece; 2Department of Ophthalmology, New York University Medical School, New York, NY, USA Purpose: To investigate epithelial thickness-distribution characteristics in a large group of keratoconic patients and their correlation to normal eyes employing anterior-segment optical coherence tomography (AS-OCT).Materials and methods: The study group (n=160 eyes) consisted of clinically diagnosed keratoconus eyes; the control group (n=160) consisted of nonkeratoconic eyes. Three separate, three-dimensional epithelial thickness maps were obtained employing AS-OCT, enabling investigation of the pupil center, average, mid-peripheral, superior, inferior, maximum, minimum, and topographic epithelial thickness variability. Intraindividual repeatability of measurements was assessed. We introduced correlation of the epithelial data via newly defined indices. The epithelial thickness indices were then correlated with two Scheimpflug imaging-derived AS-irregularity indices: the index of height decentration, and the index of surface variance highly sensitive to early and advancing keratoconus diagnosis as validation.Results: Intraindividual repeatability of epithelial thickness measurement in the keratoconic group was on average 1.67 µm. For the control group, repeatability was on average 1.13 µm. In the keratoconic group, pupil-center epithelial thickness was 51.75±7.02 µm, while maximum and minimum epithelial thickness were 63.54±8.85 µm and 40.73±8.51 µm. In the control group, epithelial thickness at the center was 52.54±3.23 µm, with maximum 55.33±3.27 µm and minimum 48.50±3.98 µm epithelial thickness. Topographic variability was 6.07±3.55 µm in the keratoconic group, while for the control group it was 1.59±0.79 µm. In keratoconus, topographic epithelial thickness change from normal, correlated tightly with the topometric asymmetry indices of IHD and ISV derived from Scheimpflug imaging.Conclusion: Simple, OCT-derived epithelial mapping, appears to have critical potential in early and advancing keratoconus diagnosis, confirmed with its correlation with established Scheimpflug-derived asymmetry topometric indices. Keywords: anterior-segment optical coherence tomography, early and advancing keratoconus, epithelial thickness imaging, novel corneal epithelial thickness-asymmetry indices, three-dimensional mapping, Scheimpflug imaging based Pentacam, topographic keratoconus grading, index of surface variance, index of height decentration

Anastasios John Kanellopoulos,1,2 George Asimellis,1 Costas Karabatsas1 1LaserVision.gr Clinical and Research Eye Institute, Athens, Greece; 2New York University Medical School, New York, NY, USA Purpose: To compare 1-year results: safety, efficacy, refractive and keratometric stability, of femtosecond myopic laser-assisted in situ keratomileusis (LASIK) with and without concurrent prophylactic high-fluence cross-linking (CXL) (LASIK-CXL).Methods: We studied a total of 155 consecutive eyes planned for LASIK myopic correction. Group A represented 73 eyes that were treated additionally with concurrent prophylactic high-fluence CXL; group B included 82 eyes subjected to the stand-alone LASIK procedure. The following parameters were evaluated preoperatively and up to 1-year postoperatively: manifest refractive spherical equivalent (MRSE), refractive astigmatism, visual acuity, corneal keratometry, and endothelial cell counts. We plotted keratometry measurements pre-operatively and its change in the early, interim and later post-operative time for the two groups, as a means of keratometric stability comparison.Results: Group A (LASIK-CXL) had an average postoperative MRSE of -0.23, -0.19, and -0.19 D for the 3-, 6-, and 12-month period, respectively, compared to -6.58±1.98 D preoperatively. Flat keratometry was 37.69, 37.66, and 37.67 D, compared to 43.94 D preoperatively, and steep keratometry was 38.35, 38.36, and 38.37 D, compared to 45.17 D preoperatively. The predictability of Manifest Refraction Spherical Equivalent (MRSE) correction showed a correlation coefficient of 0.979. Group B (stand-alone LASIK) had an average postoperative MRSE of -0.23, -0.20, and -0.27 D for the 3-, 6-, and 12-month period, respectively, compared with -5.14±2.34 D preoperatively. Flat keratometry was 37.65, 37.89, and 38.02 D, compared with 43.15 D preoperatively, and steep keratometry was 38.32, 38.57, and 38.66 D, compared with 44.07 D preoperatively. The predictability of MRSE correction showed a correlation coefficient of 0.970. The keratometric stability plots were stable for the LASIK CXL group and slightly regressing in the standard LASIK group, a novel stability evaluation metric that may escape routine acuity and refraction measurements.Conclusion: Application of prophylactic CXL concurrently with myopic LASIK surgery appears to contribute to improved refractive and keratometric stability compared to standard LASIK. The procedure appears safe and provides a new potential for LASIK correction. Keywords: myopic LASIK regression, femtosecond myopic LASIK, LASIK-CXL, LASIK-Xtra, high myopia, accelerated high-fluence collagen cross-linking

Anastasios John Kanellopoulos,1,2 George Asimellis11Laservision.gr Eye Institute, Athens, Greece; 2New York University School of Medicine, New York, NY, USA Purpose: To investigate, by high-precision digital analysis of data provided by Scheimpflug imaging, changes in pupil size and shape and anterior chamber (AC) parameters following cataract surgery.Patients and methods: The study group (86 eyes, patient age 70.58±10.33 years) was subjected to cataract removal surgery with in-the-bag intraocular lens implantation (pseudophakic). A control group of 75 healthy eyes (patient age 51.14±16.27 years) was employed for comparison. Scheimpflug imaging (preoperatively and 3 months postoperatively) was employed to investigate central corneal thickness, AC depth, and AC volume. In addition, by digitally analyzing the black-and-white dotted line pupil edge marking in the Scheimpflug “large maps,” the horizontal and vertical pupil diameters were individually measured and the pupil eccentricity was calculated. The correlations between AC depth and pupil shape parameters versus patient age, as well as the postoperative AC and pupil size and shape changes, were investigated.Results: Compared to preoperative measurements, AC depth and AC volume of the pseudophakic eyes increased by 0.99±0.46 mm (39%; P

Anastasios John Kanellopoulos LaserVision.gr Institute, Athens, Greece, and New York Medical School, New York, NY, USA Background: The purpose of this study is to report the safety and efficacy of a new application of collagen cross-linking using a novel device to achieve predictable refractive myopic changes in virgin corneas. Methods: Four cases were treated with a novel device employing very high-fluence collagen cross-linking applied in a myopic pattern. Prior to treatment, riboflavin solution was applied to the intact epithelium. The collagen cross-linking device was then engaged for a total of 12 J/cm2, to be applied transepithelially in a predetermined pattern. Cornea clarity, corneal keratometry, and corneal topography were evaluated by both Placido disc and Scheimpflug imaging, along with cornea anterior segment optical coherence tomography and endothelial cell counts. Results: An average of 2.3 diopters was achieved in the first week in all four cases treated with the very high-fluence myopic collagen cross-linking intervention. There was a slight regression to 1.44 diopters at 1 month, which remained stable at 6-month follow-up. The mean keratometry change was from 44.90 diopters to 43.46 diopters. There was no significant change in endothelial cell counts or corneal clarity. There was some mild change in epithelial thickness distribution, with the treated area showing a slight but homogeneous reduction in mean thickness from 52 µm to 44 µm. Conclusion: This report describes the novel application of very high-fluence collagen cross-linking with a predictable well defined myopic refractive (flattening) corneal effect. This technique has the advantages of essentially no postoperative morbidity, immediate visual rehabilitation, and the potential for tapering until the desired result is achieved. Keywords: myopia, refractive correction, high-fluence collagen cross-linking, clinical results

Anastasios John Kanellopoulos,1,2 George Asimellis1 1Laservision.gr Eye Institute, Athens, Greece; 2New York University Medical School, New York, NY, USA Background: The purpose of this study was to compare and correlate central corneal thickness in healthy, nonoperated eyes with three advanced anterior-segment imaging systems: a high-resolution Scheimpflug tomography camera (Oculyzer II), a spectral-domain anterior-segment optical coherence tomography (AS-OCT) system, and a high-frequency ultrasound biomicroscopy (HF-UBM) system. Methods: Fifty eyes randomly selected from 50 patients were included in the study. Inclusion criteria were healthy, nonoperated eyes examined consecutively by the same examiner. Corneal imaging was performed by three different methods, ie, Oculyzer II, spectral-domain AS-OCT, and FH-UBM. Central corneal thickness measurements were compared using scatter diagrams, Bland-Altman plots (with bias and 95% confidence intervals), and two-paired analysis. Results: The coefficient of determination (r2) between the Oculyzer II and AS-OCT measurements was 0.895. Likewise, the coefficient was 0.893 between the Oculyzer II and HF-UBM and 0.830 between the AS-OCT and HF-UBM. The trend line coefficients of linearity were 0.925 between the Oculyzer II and the AS-OCT, 1.006 between the Oculyzer II and HF-UBM, and 0.841 between the AS-OCT and HF-UBM. The differences in average corneal thickness between the three pairs of CCT measurements were –6.86 µm between the Oculyzer II and HF-UBM, –12.20 µm between the AS-OCT and Oculyzer II, and +19.06 µm between the HF-UBM and AS-OCT. Conclusion: The three methods used for corneal thickness measurement are highly correlated. Compared with the Scheimplug and ultrasound devices, the AS-OCT appears to report a more accurate, but overally thinner corneal pachymetry. Keywords: anterior eye segment, high-frequency ultrasound biomicroscopy, optical coherence tomography, high-resolution Pentacam, corneal thickness

Anastasios John KanellopoulosLaserVision gr Institute, Athens, Greece; New York University Medical School, New York, NY, USAPurpose: To report the safety and efficacy of a novel surgical technique using two lasers in cataract surgery.Methods: In this contralateral eye report, a 57-year-old female underwent cataract extraction. Two laser devices and a standard phacoemulsification, platform were used to conduct the procedures. First, a femtosecond laser was used to perform the corneal incision, capsulorhexis, and initial lens fragmentation in each eye. Following this, a nanosecond laser was used to enter the 2.8 mm incision, uni-axially, and complete the viscoelastic-divided nucleus fragment emulsification and removal in one eye. Standard phacoemulsification was used in the completion of the other eye. Posterior chamber foldable acrylic intraocular lenses were implanted in both cases. We evaluated perioperative acuity, refraction, keratometry, Scheimpflug tomography, intraocular pressure, endothelial cell counts, and total energy used with each laser in each case.Results: Corrected distance visual acuity improved from preoperative 20/60 and 20/70 to postoperative 20/20 in both eyes, with 6-month follow-up. In the right eye, the total intraocular energy used was 2 J by the femtosecond laser and 6 J by the phacoemulsification device. In the left eye, the nanosecond laser utilized the same energy of 2 J and the nanosecond laser 2.4 J (80 pulses of 30 mJ each). There were no other differences noted in intraocular pressure or endothelial cell counts.Conclusion: In this report, we introduce a bladeless all-laser cataract surgery extraction alternative technique, with several potential novel advantages: enhanced incision and capsulorhexis reproducibility, reduction in intraocular energy used, and elimination of the potential of thermal corneal injury.Keywords: LenSx® femtosecond laser, Cetus nanosecond laser, energy consumed, small-incision cataract surgery

Anastasios John Kanellopoulos,1,2 George Asimellis1 1Laservision.gr Eye Institute, Athens, Greece; 2New York University School of Medicine, New York, NY, USA Purpose: To survey the standard keratoconus grading scale (Pentacam®-derived Amsler–Krumeich stages) compared to corneal irregularity indices and best spectacle-corrected distance visual acuity (CDVA). Patients and methods: Two-hundred and twelve keratoconus cases were evaluated for keratoconus grading, anterior surface irregularity indices (measured by Pentacam imaging), and subjective refraction (measured by CDVA). The correlations between CDVA, keratometry, and the Scheimpflug keratoconus grading and the seven anterior surface Pentacam-derived topometric indices – index of surface variance, index of vertical asymmetry, keratoconus index, central keratoconus index, index of height asymmetry, index of height decentration, and index of minimum radius of curvature – were analyzed using paired two-tailed t-tests, coefficient of determination (r2), and trendline linearity. Results: The average ± standard deviation CDVA (expressed decimally) was 0.626 ± 0.244 for all eyes (range 0.10–1.00). The average flat meridian keratometry was (K1) 46.7 ± 5.89 D; the average steep keratometry (K2) was 51.05 ± 6.59 D. The index of surface variance and the index of height decentration had the strongest correlation with topographic keratoconus grading (P< 0.001). CDVA and keratometry correlated poorly with keratoconus severity. Conclusion: It is reported here for the first time that the index of surface variance and the index of height decentration may be the most sensitive and specific criteria in the diagnosis, progression, and surgical follow-up of keratoconus. The classification proposed herein may present a novel benchmark in clinical work and future studies. Keywords: diagnosis and classification, Pentacam topometric indices, Amsler–Krumeich keratoconus grading, surface variance, vertical asymmetry, keratoconus index, central keratoconus index, height asymmetry, height decentration, minimum radius of curvature

Anastasios John Kanellopoulos,1,2 George Asimellis11Laservision.gr Eye Institute, Athens, Greece; 2New York University School of Medicine, Department of Opthalmology, NY, NY, USABackground: The purpose of this study was to compare the safety and efficacy of two alternative corneal topography data sources used in topography-guided excimer laser normalization, combined with corneal collagen cross-linking in the management of keratoconus using the Athens protocol, ie, a Placido disc imaging device and a Scheimpflug imaging device.Methods: A total of 181 consecutive patients with keratoconus who underwent the Athens protocol between 2008 and 2011 were studied preoperatively and at months 1, 3, 6, and 12 postoperatively for visual acuity, keratometry, and anterior surface corneal irregularity indices. Two groups were formed, depending on the primary source used for topoguided photoablation, ie, group A (Placido disc) and group B (Scheimpflug rotating camera). One-year changes in visual acuity, keratometry, and seven anterior surface corneal irregularity indices were studied in each group.Results: Changes in visual acuity, expressed as the difference between postoperative and preoperative corrected distance visual acuity were +0.12 ± 0.20 (range +0.60 to -0.45) for group A and +0.19 ± 0.20 (range +0.75 to -0.30) for group B. In group A, K1 (flat keratometry) changed from 45.202 ± 3.782 D to 43.022 ± 3.819 D, indicating a flattening of -2.18 D, and K2 (steep keratometry) changed from 48.670 ± 4.066 D to 45.865 ± 4.794 D, indicating a flattening of -2.805 D. In group B, K1 (flat keratometry) changed from 46.213 ± 4.082 D to 43.190 ± 4.398 D, indicating a flattening of -3.023 D, and K2 (steep keratometry) changed from 50.774 ± 5.210 D to 46.380 ± 5.006 D, indicating a flattening of -4.394 D. For group A, the index of surface variance decreased to -5.07% and the index of height decentration to -26.81%. In group B, the index of surface variance decreased to -18.35% and the index of height decentration to -39.03%. These reductions indicate that the corneal surface became less irregular (index of surface variance) and the “cone” flatter and more central (index of height decentration) postoperatively.Conclusion: Of the two sources of primary corneal data, the Scheimpflug rotating camera (Oculyzer™) for topography-guided normalization treatment with the WaveLight excimer laser platform appeared to provide more statistically significant improvement than the Placido disc topographer (Topolyzer™). Overall, the Athens protocol, aiming both to halt progression of keratoconic ectasia and to improve corneal topometry and visual performance, produced safe and satisfactory refractive, keratometric, and topometric results. The observed changes in visual acuity, along with keratometric flattening and topometric improvement, are suggestive of overall postoperative improvement.Keywords: Athens protocol, anterior Pentacam indices, keratoconus, cross-linking, WaveLight/Alcon excimer laser, EX500 excimer laser, higher fluence collagen cross-linking

A John Kanellopoulos,1,2 George Asimellis1 1LaserVision.gr Eye Institute, Athens, Greece; 2New York University School of Medicine, NY, USA Purpose: To evaluate the safety and efficacy of a novel LASIK flap patient interface (PI) cone with our reported digital analysis and compare for potential differences with the standard metal and glass PI in flap parameters when used with the Alcon/WaveLight FS200 femtosecond laser. Patients and methods: Thirty-six consecutive LASIK patients (72 eyes) subjected to a bilateral femtosecond assisted LASIK procedure with the novel clear cone PI FS200 1505 were examined for flap diameter and flap thickness over the entire flap area via digital analysis performed on intraoperation image (flap diameter) and anterior-segment optical coherence tomography image (flap thickness). This group was compared with an age- and procedure-matched group B from our practice, in which the standard metal and glass PI was employed. Results: Horizontal flap diameter for group A (clear cone) was 7.87 mm ± 0.02 mm (range 7.89–7.84 mm) for 8.00 mm programmed, whereas for group B (metal and glass cone) was 7.85 mm ± 0.04 mm (range 7.93–7.80 mm). Likewise, along the vertical line, flap diameter for group A was 7.84 mm ± 0.02 mm (range 7.85–7.80 mm) and for group B was 7.83 mm ± 0.03 mm (range 7.87–7.80 mm). Central flap thickness for group A was 113.29 µm (±1.19 µm) for 110 µm planned, 122.1 µm (±2.10 µm) for 120 µm planned, and 133.50 µm (±0.71 µm) for 130 µm planned. Group B central flap thickness was, accordingly, 112.8 µm (±1.25 µm), 122.4 µm (±2.15 µm), and 132.50 µm (±0.90 µm). The data evaluated (paired group comparisons) between group A and group B did not show statistically significant differences. Conclusion: This study indicates that two PIs in use with the FS200 femtosecond laser are safe and have highly reproducible and accurate flap parameter results, such as achieved diameter and flap thickness. The paired group comparisons between the two PIs’ respective data do not show statistically significant differences. Keywords: femtosecond laser precision, bladeless LASIK, corneal flap diameter, flap thickness, Alcon/WaveLight FS200, clear cone, patient interface, applanation cone, myopic laser correction, hyperopic laser correction

A John Kanellopoulos,1,2 George Asimellis1 1Laservision.gr Institute, Athens, Greece; 2NYU Medical School, New York, USA Purpose: To evaluate programmed versus achieved laser-assisted in situ keratomileusis (LASIK) flap central thickness and investigate topographic flap thickness variability, as well as the effect of potential epithelial remodeling interference on flap thickness variability. Patients and methods: Flap thickness was investigated in 110 eyes that had had bilateral myopic LASIK several years ago (average 4.5 ± 2.7 years; range 2–7 years). Three age-matched study groups were formed, based on the method of primary flap creation: Group A (flaps made by the Moria Surgical M2 microkeratome [Antony, France]), Group B (flaps made by the Abbott Medical Optics IntraLase™ FS60 femtosecond laser [Santa Ana, CA, USA]), and Group C (flaps made by the Alcon WaveLight® FS200 femtosecond laser [Fort Worth, TX, USA]). Whole-cornea topographic maps of flap and epithelial thickness were obtained by scanning high-frequency ultrasound biomicroscopy. On each eye, topographic flap and epithelial thickness variability was computed by the standard deviation of thickness corresponding to 21 equally spaced points over the entire corneal area imaged. Results: The average central flap thickness for each group was 138.33 ± 12.38 µm (mean ± standard deviation) in Group A, 128.46 ± 5.72 µm in Group B, and 122.00 ± 5.64 µm in Group C. Topographic flap thickness variability was 9.73 ± 4.93 µm for Group A, 8.48 ± 4.23 µm for Group B, and 4.84 ± 1.88 µm for Group C. The smaller topographic flap thickness variability of Group C (FS200) was statistically significant compared with that of Group A (M2) (P = 0.004), indicating improved topographic flap thickness consistency – that is, improved precision – over the entire flap area affected. Conclusions: The two femtosecond lasers produced a smaller flap thickness and reduced variability than the mechanical microkeratome. In addition, our study suggests that there may be a significant difference in topographic flap thickness variability between the results achieved by the two femtosecond lasers examined. Keywords: Moria M2, IntraLase FS60, WaveLight® FS200, Allegretto Wave® Eye-Q, 400 Hz excimer, ultrasound biomicroscopy

A John Kanellopoulos,1,2 George Asimellis1 1Laservision.gr Eye Institute, Athens, Greece; 2New York University School of Medicine, New York, NY, USA Background: The purpose of this study is to evaluate the extent and incidence of opaque bubble layer (OBL) using laser-assisted in situ keratomileusis (LASIK) flaps created with the Alcon/WaveLight® FS200 femtosecond laser as a result of a recent change in flap programming parameters aiming to reduce further the incidence and extent of OBL. Methods: Intraoperative digital images of flaps from 36 consecutive patients (72 eyes) subjected to bilateral femtosecond-assisted LASIK were analyzed using a proprietary computerized technique. The incidence and extent of OBL was measured and reported as a percentage of the entire flap area. Flap creation was performed with a 1.7 mm wide canal, implemented as an updated design intended to reduce the extent of OBL (group A). The same OBL parameters were investigated and compared in an age-matched and procedure-matched patients in whom the previous standard setting of a 1.3 mm wide canal was implemented (group B). Results: In group A, the average extent of OBL was 3.69% of the flap area (range 0%–11.34%). In group B, the respective values were 6.06% (range 0%–20.24%). We found the difference to be statistically significant (one-tailed P = 0.00452). Conclusion: This study suggests that there is a significant reduction in the incidence and extent of OBL when novel LASIK flap ventilation canal parameters of width and spot line separation are used. Keywords: femtosecond laser flap, bladeless laser-assisted in situ keratomileusis, opaque bubble layer, Alcon/WaveLight FS200, spot line separation

A John Kanellopoulos,1,2 George Asimellis11Laservision.gr Institute, Athens, Greece; 2NYU Medical School, NY, USAPurpose: The evaluation of the safety, efficacy, and long-term stability of LASIK procedures utilizing novel platform comprising a femtosecond and excimer laser and multiple networked diagnostics.Setting: Private clinical ophthalmology practice.Patients and methods: In consecutive cases of myopic LASIK procedure with a novel refractive platform (FS200 Femtosecond and EX500 Excimer Laser), 190 eyes (from 109 different patients) were evaluated pre- and postoperatively for the following parameters: refractive error, best corrected distance visual acuity, uncorrected distance visual acuity, topography (Placido-disc based) and tomography (Scheimpflug-image based), wavefront analysis, pupillometry, and contrast sensitivity. Follow-up visits were conducted for at least 12-months.Results: The change from pre- to postoperative mean refractive error was from −5.29 ± 2.39 diopters (D) (range −8.0 to −0.50 D) to −0.27 ± 0.09 D at the 3 month visit, −0.27 ± 0.10 D at the 6 month visit, and −0.39 ± 0.08 D at the 1-year visit. The change from pre- to postoperative refractive astigmatism was −1.07 ± 0.91 D (range −4.25 to 0 D) to −0.14 ± 0.04 D at 3 months, −0.15 ± 0.04 at 6 months, and −0.16 ± 0.04 at the one-year visit. The proportion of the eyes with postoperative astigmatism within 0.5 D ranged between 95.6% and 99%. The proportion of eyes achieving uncorrected distance visual acuity of 1.0 (decimal) was 93.0%.Conclusion: The myopic LASIK clinical results with the FS200 Femtosecond Laser and EX500 Excimer Laser showed outstanding efficacy, great safety, and long-term stability.Keywords: bladeless LASIK flap, femtosecond laser, myopic correction, long-term stability, regression, astigmatism correction, post-LASIK refraction

A John Kanellopoulos1,2 George Asimellis11Laservision.gr Institute, Athens, Greece; 2New York University Medical School, New York, NY, USAPurpose: To introduce a novel, noninvasive technique to determine the depth and extent of anterior corneal stroma changes induced by collagen cross-linking (CXL) using quantitative analysis of high-resolution anterior-segment optical coherence tomography (OCT) post-operative images.Setting: Private clinical ophthalmology practice.Patients and methods: Two groups of corneal cross-sectional images obtained with the OptoVue RTVue anterior-segment OCT system were studied: group A (control) consisted of unoperated, healthy corneas, with the exception of possible refractive errors. The second group consisted of keratoconic corneas with CXL that were previously operated on. The two groups were investigated for possible quantitative evidence of changes induced by the CXL, and specifically, the depth, horizontal extent, as well as the cross-sectional area of intrastromal hyper-reflective areas (defined in our study as the area consisting of pixels with luminosity greater than the mean +2 × standard deviation of the entire stromal cross section) within the corneal stroma.Results: In all images of the second group (keratoconus patients treated with CXL) there was evidence of intrastromal hyper-reflective areas. The hyper-reflective areas ranged from 0.2% to 8.8% of the cross-sectional area (mean ± standard deviation; 3.46% ± 1.92%). The extent of the horizontal hyper-reflective area ranged from 4.42% to 99.2% (56.2% ± 23.35%) of the cornea image, while the axial extent (the vertical extent in the image) ranged from 40.00% to 86.67% (70.98% ± 7.85%). There was significant statistical difference (P < 0.02) in these values compared to the control group, in which, by application of the same criteria, the same hyper-reflective area (owing to signal noise) ranged from 0.00% to 2.51% (0.74% ± 0.63%).Conclusion: Herein, we introduce a novel, noninvasive, quantitative technique utilizing anterior segment OCT images to quantitatively assess the depth and cross-sectional area of CXL in the corneal stroma based on digital image analysis. Mean cross-sectional area showing evidence of CXL was 3.46% ± 1.92% of a 6 mm long segment.Keywords: Collagen cross-linking, keratoconus, optical coherence tomography, higher fluence cross-linking, cornea ectasia, Athens Protocol

A John Kanellopoulos,1,2 George Asimellis11Laservision Eye Institute, Athens, Greece; 2New York University School of Medicine, New York, NY, USABackground: The purpose of this study was to determine flap parameter accuracy, extent of the opaque bubble layer, and incidence of skip lines in femtosecond laser-assisted stromal in situ keratomileusis (LASIK) using the WaveLight® FS200 laser and optoelectronic clinical measurements.Methods: Images from 101 flaps were automatically recorded during consecutive routine LASIK procedures performed using the WaveLight FS200 femtosecond laser and the EX500 excimer laser. Digital processing of these images was used to evaluate objectively the diameter of FS200-created flaps, by comparing planned versus achieved procedures and to evaluate the incidence and extent (area) of the opaque bubble layer.Results: The intended flap diameters were between 8.00 mm and 9.50 mm. The achieved flap diameters showed extremely high precision, and were on average -0.16 ± 0.04 mm smaller for a 8.00 mm intended flap diameter, -0.12 ± 0.03 mm smaller for a 8.50 mm flap, and up +0.06 ± 0.06 mm wider for a 9.50 mm flap. With an average flap area of 72.4 mm2, the mean area of the opaque bubble layer (4.1 ± 4.3 [range 0–14.34] mm2) corresponded to a 6% opaque bubble layer-to-flap area. Specifically, 80% of the femtosecond-created flaps had an essentially zero opaque bubble layer (

Bradley M Mitchell,1 A John Kanellopoulos,2 Ramon L Font31Eclipse IS Consulting, Rosenberg, TX, 2Department of Ophthalmology, New York University Medical School, New York City, NY, 3Department of Ophthalmology, Ophthalmic Pathology Laboratory, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USAAbstract: This case report describes the clinical and histopathologic features, including molecular confirmation, of fungal keratitis after intrastromal corneal ring segments placement for keratoconus. A 52-year-old woman underwent insertion of Intacs® corneal implants for treatment of keratoconus. Extrusion of the implants was noted 5 months post insertion and replaced. Three months later, monocular infiltrates and an epithelial defect were observed. The Intacs were removed and the infiltrates were treated with ofloxacin and prednisolone acetate. Microbial cultures and stains were negative. The patient demonstrated flares and exacerbation one month later. Mycoplasma and/or fungus were suspected and treated without improvement. Therapeutic keratoplasty was performed 10 months following initial placement of the corneal ring implants. The keratectomy specimen was analyzed by light microscopy and a panfungal polymerase chain reaction assay. A histopathologic diagnosis of Candida parapsilosis keratitis was made and confirmed by polymerase chain reaction. One year postoperatively, a systemic workup of the patient was done with no signs of recurrence. This rare report of fungal keratitis following Intacs insertion is the first reported case of C. parapsilosis complicating Intacs implantation.Keywords: keratoconus, Intacs®, polymerase chain reaction, PCR, molecular diagnosis, histopathology

Anastasios John KanellopoulosLaservision.gr Institute, Athens, Greece, and New York University Medical School, New York, NY, USABackground: The purpose of this study was to evaluate the safety and efficacy of ultraviolet A irradiation cross-linking on completion for cases of high myopic laser-assisted in situ keratomileusis (LASIK).Methods: Forty-three consecutive LASIK cases treated with femtosecond laser flap and the WaveLight excimer platform were evaluated perioperatively for uncorrected visual acuity, best corrected spectacle visual acuity, refraction, keratometry, topography, total and flap pachymetry, corneal optical coherence tomography, and endothelial cell count. All eyes at the completion of LASIK had cross-linking through the repositioned flap, with higher fluence (10 mW/cm2) ultraviolet light of an average 370 µm wavelength and 10 mW/cm2 fluence applied for 3 minutes following an earlier single instillation of 0.1% riboflavin within the flap interface. Mean follow-up duration was 3.5 (range 1.0–4.5) years.Results: Mean uncorrected visual acuity changed from 0.2 to 1.2, best corrected spectacle visual acuity from 1.1 to 1.2, spherical equivalent from -7.5 diopters (D) to -0.2 D, keratometry from 44.5 D to 38 D, flap pachymetry from 105 µm to, total pachymetry from 525 to 405, and endothelial cell count from 2750 to 2800. None of the cases developed signs of ectasia or significant regression during follow-up.Conclusion: Prophylactic collagen cross-linking for high-risk LASIK cases appears to be a safe and effective adjunctive treatment for refractive regression and potential ectasia. This application may be viewed as prophylactic customization of the biomechanical behavior of corneal collagen.Keywords: prophylactic collagen cross-linking, laser-assisted in situ keratomileusis, high-risk, post-LASIK ectasia

Anastasios John KanellopoulosDepartment of Ophthalmology, New York University Medical School, New York, NY, and LaserVision.gr Eye Institute, Athens, GreeceBackground: The purpose of this study was to evaluate the safety and efficacy of topography-guided ablation using the WaveLight 400 Hz excimer laser in laser-assisted in situ keratomileusis (LASIK) for hyperopia and/or hyperopic astigmatism.Methods: We prospectively evaluated 208 consecutive LASIK cases for hyperopia with or without astigmatism using the topography-guided platform of the 400 Hz Eye-Q excimer system. The mean preoperative sphere value was +3.04 ± 1.75 (range 0.75–7.25) diopters (D) and the mean cylinder value was –1.24 ± 1.41 (–4.75–0) D. Flaps were created either with Intralase FS60 (AMO, Irvine, CA) or FS200 (Alcon, Fort Worth, TX) femtosecond lasers. Parameters evaluated included age, preoperative and postoperative refractive error, uncorrected distance visual acuity, corrected distance visual acuity, flap diameter and thickness, topographic changes, higher order aberration changes, and low contrast sensitivity. These measurements were repeated postoperatively at regular intervals for at least 24 months.Results: Two hundred and two eyes were available for follow-up at 24 months. Uncorrected distance visual acuity improved from 5.5/10 to 9.2/10. At 24 (8–37) months, 75.5% of the eyes were in the ±0.50 D range and 94.4% were in the ±1.00 D range of the refractive goal. Postoperatively, the mean sphere value was –0.39 ± 0.3 and the cylinder value was –0.35 ± 0.25. Topographic evidence showed that ablation was made in the visual axis and not in the center of the cornea, thus correlating with the angle kappa. No significant complications were encountered in this small group of patients.Conclusion: Hyperopic LASIK utilizing the topography-guided platform of the 400 Hz Eye-Q Allegretto excimer and a femtosecond laser flap appears to be safe and effective for correction of hyperopia and/or hyperopic astigmatism. The results are impressive for refractive error correction and stability and for improvement of both uncorrected and corrected distance visual acuity.Keywords: topography-guided, LASIK, hyperopia, hyperopic astigmatism, mixed astigmatism, angle kappa

Anastasios John Kanellopoulos,1,2 Ioannis M Aslanides,3 George Asimellis11Laservision Eye Institute, Athens, 2Emmetropia Mediterranean Eye Clinic, Crete, Greece, 3New York University School of Medicine, NY, USAPurpose: To determine and correlate epithelial corneal thickness (pachymetric) measurements taken with a digital arc scanning very high frequency ultrasound biomicroscopy (HF UBM) imaging system (Artemis-II), and compare mean and central epithelial thickness among normal eyes, untreated keratoconic eyes, and keratoconic eyes previously treated with collagen crosslinking (CXL).Methods: Epithelial pachymetry measurements (topographic mapping) were conducted on 100 subjects via HF UBM. Three groups of patients were included: patients with normal eyes (controls), patients with untreated keratoconic eyes, and patients with keratoconic eyes treated with CXL. Central, mean, and peripheral corneal epithelial thickness was examined for each group, and a statistical study was conducted.Results: Mean, central, and peripheral corneal epithelial thickness was compared between the three groups of patients. Epithelium thickness varied substantially in the keratoconic group, and in some cases there was a difference of up to 20 µm between various points of the same eye, and often a thinner epithelium coincided with a thinner cornea. However, on average, data from the keratoconic group suggested an overall thickening of the epithelium, particularly over the pupil center of the order of +3 µm, while the mean epithelium thickness was on average +1.1 µm, compared to the control population (P = 0.005). This overall thickening was more pronounced in younger patients in the keratoconic group. Keratoconic eyes previously treated with CXL showed, on average, virtually the same average epithelium thickness (mean –0.7 µm, –0.2 µm over the pupil center, –0.9 µm over the peripheral zone) as the control group. This finding further reinforces our novel theory of the “reactive” component of epithelial thickening in corneas that are biomechanically unstable, becoming stable when biomechanical rigidity is accomplished despite persistence of cornea topographic irregularity.Conclusion: A highly irregular epithelium may be suggestive of an ectatic cornea. Our results indicate that the epithelium is thinner over the keratoconic protrusion, but to a much lesser extent than anticipated, and on average epithelium is thicker in this group of patients. This difference appears to be clinically significant and may become a screening tool for eyes suspected for ectasia.Keywords: corneal pachymetry, ectasia, keratoconus screening, cornea epithelial thickness

Anastasios John, KanellopoulosLaserVision gr Institute, Athens, Greece; New York University Medical School, New York City, NY, USABackground: This research comprised a laboratory evaluation of a novel refractive surgery technique involving sequential corneal subsurface shrinkage-driven reshaping using a continuous wave mid-infrared laser application followed by stiffening via rapid transepithelial higher fluence collagen cross-linking for shape persistence/longevity on cadaver corneas.Materials and methods: Ten cadaver corneas were used in this study. During use, all were affixed in an artificial chamber. Thermal delivery entailed a continuous wave laser at 2013 nm wavelength, approximately 650 mW power under scanner control (about 3 mm/sec linear draw speed), with a planoconcave sapphire applanation lens cooled to 8°C. Group 1 (n = 5, myopic treatment) eyes were exposed to three concentric annuli with diameters of 3 mm, 4 mm, and 5 mm. Group 2 (n = 5, hyperopic treatment) eyes were exposed to three concentric annuli with diameters of 6 mm, 7 mm, and 8 mm. The clinical change in shape of the cornea was visualized immediately under a slit-lamp. A transepithelial higher fluence corneal collagen cross-linking step followed each thermal treatment, comprising 0.1% riboflavin drops with 0.02% benzalkonium chloride and 0.2% carboxymethlycellulose in deuterated water (D2O) applied on the epithelium corneal surface for 10 minutes. Next, each cornea was exposed to 10 mW/cm2 of ultraviolet A (365 nm) light for 10 minutes. The corneas were evaluated before and after thermal remodeling and cornea collagen cross-linking for corneal topography, corneal optical coherence tomography, cornea Scheimpflug tomography, and clinical photographs.Results: The histopathology effect was noted clinically as concentric white rings underneath the epithelium and Bowman's membrane, with the lesion depth extending down to 400 µm in the mid stroma of the cornea. This was confirmed by corneal anterior segment optical coherence tomography. The topographic change noted was a 4–8 diopter hyperopic shift in group 1 and a 2–6 diopter myopic shift in group 2.Conclusion: This novel refractive surgery technique appears to generate a significant refractive change (+/-) in the cornea, without affecting the epithelium or Bowman's membrane and without any visible epithelial defect. The transepithelial collagen cross-linking used as a second step in the same procedure aims to stabilize this effect in the long term. Further clinical studies are planned to validate these initial clinical results.Keywords: cornea collagen shrinkage, refractive cornea change, cornea collagen cross-linking, infrared laser

Anastasios John KanellopoulosLaservision.gr Institute, Athens, Greece; Manhattan Eye, Ear and Throat Hospital, New York, NY, USA; New York University Medical School, New York, NY, USAPurpose: To evaluate the safety and efficacy of combined transepithelial topography-guided photorefractive keratectomy (PRK) therapeutic remodeling, combined with same-day, collagen cross-linking (CXL). This protocol was used for the management of cornea blindness due to severe corneal scarring.Methods: A 57-year-old man had severe corneal blindness in both eyes. Both corneas had significant central scars attributed to a firework explosion 45 years ago, when the patient was 12 years old. Corrected distance visual acuity (CDVA) was 20/100 both eyes (OU) with refraction: +4.00, –4.50 at 135° in the right eye and +3.50, –1.00 at 55° in the left. Respective keratometries were: 42.3, 60.4 at 17° and 35.8, 39.1 at 151.3°. Cornea transplantation was the recommendation by multiple cornea specialists as the treatment of choice. We decided prior to considering a transplant to employ the Athens Protocol (combined topography-guided partial PRK and CXL) in the right eye in February 2010 and in the left eye in September 2010. The treatment plan for both eyes was designed on the topography-guided wavelight excimer laser platform.Results: Fifteen months after the right eye treatment, the right cornea had improved translucency and was topographically stable with uncorrected distance visual acuity (UDVA) 20/50 and CDVA 20/40 with refraction +0.50, –2.00 at 5°. We noted a similar outcome after similar treatment applied in the left eye with UDVA 20/50 and CDVA 20/40 with –0.50, –2.00 at 170° at the 8-month follow-up.Conclusion: In this case, the introduction of successful management of severe cornea abnormalities and scarring with the Athens Protocol may provide an effective alternative to other existing surgical or medical options.Keywords: Athens Protocol, collagen cross-linking, cornea blindness, cornea scarring, photorefractive keratectomy, vision

Anastasios John Kanellopoulos1–31Laservision.gr Institute, Athens, Greece; 2Manhattan Eye, Ear and Throat Hospital, New York, NY, 3New York University Medical School, New York, NY, USAPurpose: To evaluate the safety and efficacy of higher fluence cornea collagen cross linking (CXL).Methods: Twenty-one patients with bilateral keratoconus had randomized CXL in one eye (group A) with 7 mw/cm2 for 15 minutes; the other eye (group B) had the standard 3 mw/cm2 for 30 minutes; 50 um PTK with the Eye-Q 400 Hz Excimer laser (Wavelight, Erlagen, Germany) was used for epithelial removal. The patients were evaluated postoperatively at the following intervals: day 1, day 4, month 1, month 3, and then every 6 months.Results: For groups A and B respectively, in mean values: uncorrected distance visual acuity (UDVA) improved from 20/60 to 20/38, and 20/62 to 20/40; best corrected visual acuity (BCVA) from 20/30 to 20/25 in both groups; mean sphere was reduced by 2.5 and 2.1 diopters; mean cylinder was reduced by 2.9 and 2.5 diopters on average; Steepest K was reduced from 49.5 to 46.1, and from 48.7 to 45.8 diopters. There was no ectasia progression in any of the cases during the follow-up time studied. There was no change in the endothelial cell count. All patients returned to full activities postoperatively within a month. Four cases from group A and five cases from group B had delayed epithelial healing (completed by postoperative day 9). No other adverse effects were noted in any of the cases studied. Mean follow-up was 46 months (18–56). Corneal optical coherence tomography (OCT) revealed diffused light scattered in anterior two-thirds of the cornea stroma, which was more intense and much broader in diameter in group A than in group B.Conclusion: This novel technique offers similar clinical results in ectasia stabilization without any adverse effects noted.Keywords: cornea collagen cross linking (CXL), ectasia management, keratoconus management, higher fluence ultraviolet light