Anastasios John Kanellopoulos

Collagen cross-linking (CCL) with sequential topography-guided PRK: a temporizing alternative for keratoconus to penetrating keratoplasty.

Purpose: To assess the effectiveness of ultraviolet A (UVA) irradiation-induced collagen cross-linking (CCL) on keratoconus (KC) progression. Methods: A patient with bilateral, progressive KC underwent UVA irradiation (3 mW/cm2 for 30 minutes) after topical 0.1% riboflavin drops over a deepithelialized cornea. Twelve months later, a topography-guided penetrating keratoplasty (PRK; wavelight 400 Hz Eye-Q excimer) was performed in 1 eye for a refractive error of −3.50 −4.00 × 155 by using an attempted treatment of −2.50 −3.00 × 155. At all postoperative follow-up visits to 18 months, uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), pachymetry, and topography were performed. Results: In the treated left eye, the UCVA after the UVA CCL improved from 20/100 to 20/80, and the BSCVA improved from 20/50 to 20/40. Eighteen months after the topography-guided PRK, the UCVA was 20/20, and the BSCVA was 20/15, with a refractive error of Plano −0.50 × 150. The cornea was clear, and the endothelial cell count remained unchanged. The untreated right mate eye continued to progress during the same period. Conclusions: The significant clinical improvement and the apparent stability of more than a year after UVA CCL, and subsequent PRK compared with the untreated mate eye, seems to validate this treatment approach for KC. An adjusted nomogram may be considered in the ablation of cross-linked cornea tissue to avoid overcorrections.

Comparison of sequential vs same-day simultaneous collagen cross-linking and topography-guided PRK for treatment of keratoconus.

PURPOSE The safety and efficacy of corneal collagen cross-linking (CXL) and topography-guided photorefractive keratectomy (PRK) using a different sequence and timing were evaluated in consecutive keratoconus cases. METHODS This study included a total of 325 eyes with keratoconus. Eyes were divided into two groups. The first group (n=127 eyes) underwent CXL with subsequent topography-guided PRK performed 6 months later (sequential group) and the second group (n=198 eyes) underwent CXL and PRK in a combined procedure on the same day (simultaneous group). Statistical differences were examined for pre- to postoperative changes in uncorrected (UCVA, logMAR) and best-spectacle-corrected visual acuity (BSCVA, logMAR), manifest refraction spherical equivalent (MRSE), keratometry (K), topography, central corneal thickness, endothelial cell count, corneal haze, and ectatic progression. Mean follow-up was 36+/-18 months (range: 24 to 68 months). RESULTS At last follow-up in the sequential group, the mean UCVA improved from 0.9+/-0.3 logMAR to 0.49+/-0.25 logMAR, and mean BSCVA from 0.41+/-0.25 logMAR to 0.16+/-0.22 logMAR. Mean reduction in spherical equivalent refraction was 2.50+/-1.20 diopters (D), mean haze score was 1.2+/-0.5, and mean reduction in K was 2.75+/-1.30 D. In the simultaneous group, mean UCVA improved from 0.96+/-0.2 logMAR to 0.3+/-0.2 logMAR, and mean BSCVA from 0.39+/-0.3 logMAR to 0.11+/-0.16 logMAR. Mean reduction in spherical equivalent refraction was 3.20+/-1.40 D, mean haze score was 0.5+/-0.3, and mean reduction in K was 3.50+/-1.3 D. Endothelial cell count preoperatively and at last follow-up was unchanged (P<.05) in both groups. Statistically, the simultaneous group did better (P<.05) in all fields evaluated, with improvement in UCVA and BSCVA, a greater mean reduction in spherical equivalent refraction and keratometry, and less corneal haze. CONCLUSIONS Same-day simultaneous topography-guided PRK and CXL appears to be superior to sequential CXL with later PRK in the visual rehabilitation of progressing keratoconus.

Long term results of a prospective randomized bilateral eye comparison trial of higher fluence, shorter duration ultraviolet A radiation, and riboflavin collagen cross linking for progressive keratoconus.

Purpose 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.

Collagen cross-linking in early keratoconus with riboflavin in a femtosecond laser-created pocket: initial clinical results.

PURPOSE To evaluate the safety and efficacy of a novel femtosecond laser-assisted technique for intrastromal administration of riboflavin and higher fluence ultraviolet a (UVA) light in collagen cross-linking (CXL) for keratoconus. METHODS Ten eyes with early keratoconus were treated with CXL and followed for a mean of 26 months (range: 18 to 36 months). Using a femtosecond laser, a 100-microm deep, 7-mm diameter intrastromal pocket was created. Two 0.1-mL doses of 0.1% riboflavin solution were infused into the pocket and the cornea was irradiated with 7 mW/cm2 UVA light of mean 370 nm wavelength for 15 minutes. RESULTS Mean uncorrected visual acuity improved from 20/40.5 to 20/32.5 best spectacle-corrected visual acuity was unchanged at 20/20, mean sphere was reduced by 0.50 diopters (D), mean cylinder was reduced by 0.90 D, and maximum mean keratometry (K) reduced from 48.7 to 47.90 D. No ectasia progression (defined as increase in K over 3-month follow-up) and no statistically significant change in endothelial cell count was noted during follow-up. The mean thinnest corneal thickness appeared to initially reduce but the mean returned to at least the preoperative level by 18 months. All patients returned to full activities within 1 day postoperative. No adverse effects were noted in any of the cases studies. CONCLUSIONS This novel epithelium-sparing, rapid soak-and-treat method of intrastromal riboflavin instillation and higher fluence UVA light for CXL appears to be safe and effective. No negative biomechanical effect (ectasia/epithelial ingrowth) was noted due to the femtosecond laser-created pocket. Because minimal epithelial injury occurs using this technique, postoperative pain appears to be significantly reduced.

Management of Corneal Ectasia After LASIK With Combined, Same-day, Topography- guided Partial Transepithelial PRK and Collagen Cross-linking: The Athens Protocol

PURPOSE To evaluate a series of patients with corneal ectasia after LASIK that underwent the Athens Protocol: combined topography-guided photorefractive keratectomy (PRK) to reduce or eliminate induced myopia and astigmatism followed by sequential, same-day ultraviolet A (UVA) corneal collagen cross-linking (CXL). METHODS Thirty-two consecutive corneal ectasia cases underwent transepithelial PRK (WaveLight ALLEGRETTO) immediately followed by CXL (3 mW/cm(2)) for 30 minutes using 0.1% topical riboflavin sodium phosphate. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction spherical equivalent, keratometry, central ultrasonic pachymetry, corneal tomography (Oculus Pentacam), and endothelial cell counts were analyzed. Mean follow-up was 27 months (range: 6 to 59 months). RESULTS Twenty-seven of 32 eyes had an improvement in UDVA and CDVA of 20/45 or better (2.25 logMAR) at last follow-up. Four eyes showed some topographic improvement but no improvement in CDVA. One of the treated eyes required a subsequent penetrating keratoplasty. Corneal haze grade 2 was present in 2 eyes. CONCLUSIONS Combined, same-day, topography-guided PRK and CXL appeared to offer tomographic stability, even after long-term follow-up. Only 2 of 32 eyes had corneal ectasia progression after the intervention. Seventeen of 32 eyes appeared to have improvement in UDVA and CDVA with follow-up >1.5 years. This technique may offer an alternative in the management of iatrogenic corneal ectasia.

Comparison of corneal sensation following photorefractive keratectomy and laser in situ keratomileusis.

Purpose: To evaluate the effect of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) on corneal sensation. Setting: Eye Institute, Medical School of the University of Crete, Heraklion, Greece, and Orasis, Hellenic Eye Center of Athens, Greece. Methods: In a masked study, corneal sensation was measured with the CochetBonnet aesthesiometer in 40 consecutive patients 6 to 12 months following PRK and LASIK (60 mm constitutes normal reading and <40 mm, abnormal). Results: After 6 to 12 months, the mean corneal sensation following PRK was 39.2 mm (range 30 to 55 mm) (mean 9.5 months) and after LASIK, 53.6 mm (range 40 to 60 mm) (mean 9.3 months). The mean correction attempted for PRK was 7.05 diopters (D) (range 2.5 to 12.0 D) and for LASIK, 11.71 D (range 6.0 to 20.0 D). Conclusion: In this group of patients, with correction of primarily severe myopia, corneal sensation was significantly greater after LASIK than after PRK.

Subconjunctival mitomycin C for the treatment of ocular cicatricial pemphigoid

PURPOSE The authors performed a prospective evaluation of the efficacy of treating ocular cicatricial pemphigoid (OCP) with subconjunctival mitomycin C. DESIGN Unmasked, prospective, internally controlled case series. METHODS Patients were eligible for treatment with subconjunctival mitomycin C under three criteria: (1) significant complications of systemic immunosuppressant therapy; (2) markedly asymmetric conjunctival disease; and (3) end-stage OCP. All patients received monocular subconjunctival injections of 0.25 ml of 0.2 mg/ml mitomycin C to both the superior and inferior bulbar conjunctivae in the eye with the more severe disease. RESULTS Nine eyes of nine patients (mean age, 74 years) were treated with subconjunctival mitomycin C to the more-involved eye and were followed for a mean of 23.5 months (range, 12-40 months). Eight of nine patients showed quiescence of their OCP in the treated eye based on serial evaluation of conjunctival cicatrization and grading of conjunctival erythema. Five of the nine untreated eyes showed progression of the conjunctival disease. One patient required concomitant systemic immunosuppressive therapy after subconjunctival mitomycin C. Two patients underwent successful visual rehabilitative surgery in the mitomycin C-treated eye. CONCLUSION The use of subconjunctival mitomycin C may be effective in preventing progression of conjunctival cicatrization and erythema in patients with OCP. No complications of mitomycin C treatment were noted. Long-term follow-up and further investigation into the efficacy of subconjunctival mitomycin C in the management of OCP is warranted.

Keratoconus Management: Long-Term Stability of Topography-Guided Normalization Combined With High-Fluence CXL Stabilization (The Athens Protocol)

PURPOSE To investigate refractive, topometric, pachymetric, and visual rehabilitation changes induced by anterior surface normalization for keratoconus by partial topography-guided excimer laser ablation in conjunction with accelerated, high-fluence cross-linking. METHODS Two hundred thirty-one keratoconic cases subjected to the Athens Protocol procedure were studied for visual acuity, keratometry, pachymetry, and anterior surface irregularity indices up to 3 years postoperatively by Scheimpflug imaging (Oculus Optikgeräte GmbH, Wetzlar, Germany). RESULTS Mean visual acuity changes at 3 years postoperatively were +0.38 ± 0.31 (range: -0.34 to +1.10) for uncorrected distance visual acuity and +0.20 ± 0.21 (range: -0.32 to +0.90) for corrected distance visual acuity. Mean K1 (flat meridian) keratometric values were 46.56 ± 3.83 diopters (D) (range: 39.75 to 58.30 D) preoperatively, 44.44 ± 3.97 D (range: 36.10 to 55.50 D) 1 month postoperatively, and 43.22 ± 3.80 D (range: 36.00 to 53.70 D) up to 3 years postoperatively. The average Index of Surface Variance was 98.48 ± 43.47 (range: 17 to 208) pre-operatively and 76.80 ± 38.41 (range: 7 to 190) up to 3 years postoperatively. The average Index of Height Decentration was 0.091 ± 0.053 μm (range: 0.006 to 0.275 μm) preoperatively and 0.057 ± 0.040 μm (range: 0.001 to 0.208 μm) up to 3 years postoperatively. Mean thinnest corneal thickness was 451.91 ± 40.02 μm (range: 297 to 547 μm) preoperatively, 353.95 ± 53.90 μm (range: 196 to 480 μm) 1 month postoperatively, and 370.52 ± 58.21 μm (range: 218 to 500 μm) up to 3 years postoperatively. CONCLUSIONS The Athens Protocol to arrest keratectasia progression and improve corneal regularity demonstrates safe and effective results as a keratoconus management option. Progressive potential for long-term flattening validates using caution in the surface normalization to avoid overcorrection.

Revisiting keratoconus diagnosis and progression classification based on evaluation of corneal asymmetry indices, derived from Scheimpflug imaging in keratoconic and suspect cases

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.

Long-term safety and efficacy follow-up of prophylactic higher fluence collagen cross-linking in high myopic laser-assisted in situ keratomileusis.

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