Faculty Bibliography

PURPOSE: To evaluate biomechanical changes induced by in situ corneal cross-linking (CXL) with stromal pocket delivered enhanced concentration riboflavin and high-fluence, high-energy UV-A irradiation. METHODS: Eight human donor corneas were subjected to intrastromal lamellar corneal tissue removal of anterior 140-mum deep, 80-mum thick x 5-mm diameter central stromal buttons, extracted through a 3.5-mm width tunnel, surfacing in the superior cornea periphery. Enhanced concentration riboflavin solution (0.25%) was instilled in the pocket. In study group A (CXL), superficial high-fluence UV-A irradiation was applied, whereas in control group B (no CXL), none. To comparatively assess changes in corneal rigidity, corneal specimens were subjected to transverse biaxial resistance measurements by application of a unidirectional tangential shear force. Biomechanical differences were evaluated through stress and Young shear modulus. RESULTS: Stress at 10% strain was 305 +/- 24 kPa in study group A versus 157 +/- 11 kPa in control group B (relative difference Delta = 107%, P = 0.021). Stress at 20% strain was 1284 +/- 34 kPa in study group A versus 874 +/- 29 kPa in control group B (Delta = 47%, P = 0.043). Average shear modulus in study group A at 10% strain was 6.98 +/- 1.12 MPa versus 4.04 +/- 0.85 MPa in control group B (Delta = 73%, P = 0.036). Average shear modulus in study group A at 20% strain was 11.46 +/- 0.75 MPa versus 8.80 +/- 0.72 MPa in group B (Delta = 30%, P = 0.047). CONCLUSIONS: Adjunct CXL in this ex vivo simulation refractive lens extraction procedure seems to provide significant increase in corneal rigidity, up to +107%. These findings also support our previous reported work on laser in situ keratomileusis combined with CXL.

PURPOSE/OBJECTIVE:To objectively define the effective centration of myopic femtosecond laser-assisted LASIK ablation pattern, evaluate the difference between achieved versus planned excimer laser ablation centration, and compare these results from two different generations of an excimer laser system. METHODS:The study retrospectively evaluated 280 eyes subjected to myopic LASIK. Digital image analysis was performed on Scheimpflug sagittal curvature maps (difference of preoperative to postoperative). Centration was assessed via proprietary software digital analysis of the coordinate displacement between the achieved ablation geometric center and the planned ablation center, which was the corneal vertex. Results from two different excimer laser generations (Eye-Q 400 [140 eyes] and EX500 [140 eyes]; Alcon/WaveLight, Fort Worth, TX) were compared. RESULTS:Radial displacement was on average 360 ± 220 µm (range: 0 to 1,030 µm) in the Eye-Q 400 laser group and 120 ± 110 µm (range: 0 to 580 µm) in the EX500 laser group (P < .01). The percentage of eyes with displacement of greater than 300 µm was 52% in the Eye-Q 400 laser group and 4% in the EX500 laser group. CONCLUSIONS:Displacement of ablation pattern may depend on the laser platform used. The improvement in the efficiency of centration indicates that newer generation excimer lasers with faster eye tracking and active centration control appear to achieve a significantly more accurate centration of myopic ablation patterns. The authors propose this novel, objective technique for laser refractive surgeon evaluation may point out significant outcome measures not currently used in standard metrics of refractive laser efficiency.

PURPOSE: To compare postoperative changes in apparent photopic and mesopic pupil size and centration in relation to cornea reflection landmarks after cataract surgery. SETTING: LaserVision.gr Clinical and Research Eye Institute, Athens, Greece. DESIGN: Prospective consecutive case study. METHODS: Pupils were imaged for pupil size and corneal vertex location before and 1-month after cataract surgery. Digital analysis of pupil images was used to determine the Cartesian coordinates (nasal-temporal, horizontal axis, superior-inferior, vertical axis) of the first Purkinje reflection point (approximating the corneal intersection of the visual axis [corneal vertex]) to the pupil geometric center (approximating the corneal intersection of the line of sight [corneal apex]). Pupil size changes were measured, and the correlation between vertex-to-apex shift changes and postoperative pupil centroid shift was evaluated. RESULTS: The study evaluated 40 eyes. The pupil size (diameter) change corresponded to a relative reduction of -9.8% for photopic pupils and -9.1% for mesopic pupils; the difference was statistically significant (P = .045 and P = .011, respectively). Also, there was a reduction in the centroid shift (all eyes) from a mean of 0.12 mm preoperatively to 0.05 mm postoperatively as a result of the postoperative minus temporal horizontal difference between the corneal vertex and the apex. CONCLUSIONS: Cataract extraction surgery appears to affect pupil size and centration. Specifically, a smaller pupil and less temporal shift were recorded. These data may have clinical relevance in targeted intraoperative intraocular lens centration. FINANCIAL DISCLOSURE: Dr. Kanellopoulos is a consultant to Alcon Surgical, Inc., Wavelight Laser Technologie AG, Allergan, Avedro, Inc., and i-Optics Corp. No author has a financial or proprietary interest in any material or method mentioned.

PURPOSE: 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 degrees (0.38 to 7.78 degrees ) for the LASIK Group A, 4.12+/-3.17 degrees (0.02 to 12.13 degrees ) for the keratoconic Group B, and 3.20+/-1.99 degrees (0.17 to 8.61 degrees ) for the cross-linked Group C. The control Group D had axis repeatability 2.16+/-1.39 degrees (0.05 to 5.86 degrees ). 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.

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.