Elena Albè

Refractive, topographic, tomographic, and aberrometric analysis of keratoconic eyes undergoing corneal cross-linking.

PURPOSE To report refractive, topographic, tomographic, and aberrometric outcomes 12 months after corneal cross-linking (CXL) in eyes with progressive advanced keratoconus. DESIGN Prospective, nonrandomized, single-center clinical study. PARTICIPANTS Twenty-eight eyes undergoing CXL between April and June 2006. INTERVENTION Riboflavin-ultraviolet A (UVA)-induced CXL included instillation of 0.1% riboflavin-20% dextrane solution 30 minutes before UVA irradiation and every 5 minutes for an additional 30 minutes during irradiation. MAIN OUTCOME MEASURES Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), sphere and cylinder refraction, topography, tomography, aberrometry, and endothelial cell count were evaluated at baseline and at 1, 3, 6, and 12 months follow-up. RESULTS Mean baseline UCVA and BSCVA were 0.17+/-0.09 and 0.52+/-0.17, respectively; 12-month mean UCVA and BSCVA were 0.27+/-0.08 and 0.72+/-0.16, a statistically significant difference (P<0.05). Mean spherical equivalent refraction showed a significant decrease of 0.41 diopters (D). Mean baseline simulated keratometry (SIM K) flattest and steepest meridians and SIM K average were 46.10, 50.37, and 48.08 D, respectively; at 12 months, 40.22, 44.21, and 42.01 D, respectively, were recorded, a difference that was significant for all 3 indices (P<0.05). Mean average pupillary power (APP) changed significantly from 47.50 to 41.04 D at 12 months (P<0.05) and apical keratometry (AK) from 58.94 to 55.18 D (P<0.05). The treated eyes showed no deterioration of the Klyce indices at 6 months postoperatively, whereas the untreated (contralateral) eyes did show deterioration. For a 3-mm pupil, there was a significant reduction (P<0.05) in whole eye (total), corneal, higher order, and astigmatic wavefront aberrations. A significant difference (P<0.05) in total coma and total spherical aberration after CXL was also observed. Mean baseline pupil center pachymetry and total corneal volume decreased significantly (P<0.05) to 470.09+/-29.01 microm and 57.17+/-3.21 mm(3) from baseline values of 490.68+/-30.69 microm and 59.37+/-4.36 mm(3), respectively. Endothelial cell counts did not changed significantly (P=0.13). CONCLUSIONS Corneal cross-linking seems to be effective in improving UCVA and BSCVA in eyes with progressive keratoconus by significantly reducing corneal APP, AK, and corneal and total wavefront aberrations at 1 year postoperatively.

Intraoperative and Postoperative Effects of Corneal Collagen Cross-linking on Progressive Keratoconus

OBJECTIVES To report intraoperative and 24-month refractive, topographic, tomographic, and aberrometric outcomes after corneal collagen cross-linking in progressive advanced keratoconus. METHODS Prospective, nonrandomized single-center clinical study involving 28 eyes. Main outcome measures included uncorrected and best spectacle-corrected visual acuities, sphere and cylinder refraction, topography, tomography, aberrometry, and endothelial cell count evaluated at baseline and follow-up at 1, 3, 6, 12, and 24 months after treatment. Topography was also recorded intraoperatively. RESULTS Two years after treatment, mean baseline uncorrected and best spectacle-corrected visual acuities improved significantly (P = .048 and <.001, respectively) and mean spherical equivalent refraction decreased significantly (P = .03). Mean baseline flattest and steepest meridians on simulated keratometry, simulated keratometry average, mean average pupillary power, and apical keratometry all decreased significantly (P < .03). Deterioration of the Klyce indices was observed in the untreated contralateral eyes but not in treated eyes. Total corneal wavefront aberrations Z(0) (piston), Z(2) (defocus), and Z(7) (III coma) decreased significantly (P < or = .046). Mean 12-month baseline pupil center pachymetry and total corneal volume decreased significantly (P = .045). Endothelial cell counts did not change significantly (P = .13). CONCLUSIONS Two years postoperatively, corneal collagen cross-linking appears to be effective in improving uncorrected and best spectacle-corrected visual acuities in eyes with progressive keratoconus by significantly reducing corneal average pupillary power, apical keratometry, and total corneal wavefront aberrations.

Two-Year Corneal Cross-Linking Results in Patients Younger Than 18 Years With Documented Progressive Keratoconus

PURPOSE To report refractive, topographic, aberrometric, and tomographic outcomes 24 months after corneal cross-linking (CXL) in patients up to 18 years of age with progressive keratoconus. DESIGN Prospective, interventional case series. METHODS Forty eyes underwent riboflavin-ultraviolet A-induced CXL. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), sphere and cylinder, topography, aberrometry, tomography, and endothelial cell counts were evaluated at baseline and at 1, 3, 6, 12, and 24 months. RESULTS Mean logarithm of the minimum angle of resolution baseline UCVA and BSCVA were 0.79 ± 0.21 and 0.39 ± 0.10, respectively. Mean UCVA and BSCVA at 2 years were 0.58 ± 0.18 and 0.20 ± 0.09, respectively. The improvement in UCVA and BSCVA was significant throughout the postoperative follow-up (P < .05). Mean spherical equivalent refraction showed a significant decrease of 1.57 diopters (D) at 24 months (P = .02). Mean baseline simulated keratometry was 46.32 D in the flattest meridian and 51.48 D in the steepest meridian; at 2 years, the values were 45.30 D (P = .04) and 50.21 D (P = .07), respectively. For a 3-mm pupil, there was a significant reduction (P < .05) in whole eye (total), corneal, higher-order, and astigmatic wavefront aberrations at 24 months. A significant difference (P < .05) in total coma and total spherical aberration 2 years after CXL also was observed. Mean baseline pupil center pachymetry decreased significantly (P = .04) at 6 months, but recovered by 12 months and remained stable thereafter through the 2-year follow-up. Endothelial cell counts did not change significantly (P = .32). CONCLUSIONS CXL improved UCVA and BSCVA in the study patients, most likely by significantly reducing corneal asymmetry and corneal as well as total wavefront aberrations.

Intraobserver and interobserver reproducibility in the evaluation of optic disc stereometric parameters by Heidelberg Retina Tomograph

PURPOSE To assess intraobserver and interobserver reproducibility of the measurement of stereometric parameters of the optic disc by means of the Heidelberg Retina Tomograph I (HRT). STUDY DESIGN Observational study, with interobserver variability. PARTICIPANTS Fifty-five volunteers (healthy subjects and patients with glaucoma). METHODS HRT examination of the optic disc was repeated on 3 consecutive days on 1 eye of each of the 55 subjects. During each session, five single images were randomly acquired by two independent observers. One mean topography image (MTI), based on three single images, was then built at each session. For the intraobserver intraimage evaluation, the two observers traced their own contour line on one randomly chosen MTI. This procedure was repeated three times. For the intraobserver interimage and interobserver intra/interimage evaluations, the two observers traced their own contour line on the MTI of the first session, which was then automatically superimposed on the MTIs of the other two sessions. MAIN OUTCOME MEASURES Reproducibility of the 12 stereometric parameters was calculated for each observer by means of the intraclass correlation coefficient (ICC). The expected range of variability between two independent evaluations was calculated by the scatter-plots of each test-retest difference versus their mean. The standard deviation of the mean test-retest score differences was used to describe the spread of score differences. RESULTS The ICC ranged between 0.79 and 0.99 for intraobserver intraimage and between 0.56 and 1 for intraobserver interimage evaluation. The ICC ranged between 0.54 and 0.99 for interobserver intraimage and between 0.65 and 0.97 for the interobserver interimage evaluation. ICC was almost perfect to perfect for planimetric measures (0.81 < ICC < or = 1), substantial to almost perfect for volumetric and cup measures (0.61 < ICC < or = 0.99), and moderate to almost perfect for retinal nerve fiber layer related measures (0.41 < ICC < 0.99). The expected variability was low (95% confidence interval, < +/-9%). Interimage evaluation showed a higher variability than intraimage evaluation in both of interobserver (P = 0.012) and intraobserver evaluation (P = 0.028 and P = 0.031 for the two observers). CONCLUSIONS Measurement of optic disc stereometric parameters by HRT is highly reproducible. However, the use of retinal nerve fiber layer-related parameters should be taken cautiously. The image acquisition-induced variability seems larger than the operator-induced variability.

Corneal collagen cross-linking for ectasia after excimer laser refractive surgery: 1-year results

PURPOSE To evaluate the 1-year results of corneal collagen cross-linking (CXL) in eyes with postoperative excimer laser refractive surgery corneal ectasia. METHODS Thirteen eyes of 9 consecutive patients who had undergone excimer laser refractive surgery (photorefractive keratectomy [n = 3], LASIK [n = 10]) with resultant unstable corneal ectasia underwent CXL with photosensitizing riboflavin 0.1% solution and subsequent exposure to ultraviolet radiation. Study eyes underwent complete ophthalmologic examination, endothelial specular microscopy, corneal topography, and aberrometry as well as central pachymetry and Scheimpflug-based topo/tomography preoperatively and at 3-, 6-, and 12-month intervals. RESULTS Best spectacle-corrected visual acuity (BSCVA) improvement was statistically significant (P < .05) beyond 6 months after surgery (improvement of 0.1 logMAR at 1 year). Mean spherical equivalent refraction and mean refractive sphere reduction (improvement of 1.40 and 1.44 diopters [D], respectively) were statistically significant (P < .05) at 6 months postoperatively. At 1 year after CXL, mean endothelial cell count and keratometry (average SimK decrease of 2.02 D) as well as Klyce and Ambrósio indices did not deteriorate. Coma and spherical aberration did not change significantly. Mean pupil center pachymetry and corneal thickness at 0 and 2 mm from the thinnest corneal point decreased significantly. CONCLUSIONS One year after surgery, CXL appears to stabilize eyes with ectasia consequent to excimer laser refractive surgery and improve BSCVA.

Corneal Topography-Guided Penetrating Keratoplasty and Suture Adjustment New Approach for Astigmatism Control

Purpose: To describe a new keratoplasty procedure using intraoperative topography to reduce postoperative astigmatism. Methods: One hundred sixty-five eyes of 150 consecutive patients were enrolled in this prospective study. The most common diagnosis was keratoconus (78.8%). As many as 5.5% had post-laser in situ keratomileusis ectasia. Keratoplasty was performed with the Hanna Corneal Trephine System. A 24-bite running suture was placed, using a specially developed marker. Suture adjustment was performed with the aid of an intraoperative topographer (Keratron Scout; OPTIKON 2000, Rome, Italy). The aim of the adjustment was to obtain an astigmatism ≤2.0 D on the operating table. In case of >3.0 D of astigmatism at 1 month after surgery, suture adjustment was performed using the same intraoperative topographer. Results: At 12 months postoperatevely (suture in), data from 108 (64%) eyes were available. The mean refractive astigmatism was 3.53 D, and the mean topographical astigmatism was 4.7 D. At 18 months (suture out), data from 32 eyes (19.4%) were available, and at 24 months, data from 29 eyes (13.3%) were available. The mean refractive astigmatism was 3.39 D at 18 months and 3.47 D at 24 months. The mean topographic astigmatism was 2.30 D at 18 months and 1.76 D at 24 months. Mean best spectacle-corrected visual acuity (BSCVA) was 0.51 at 3 months, 0.63 at 12 months (suture in), 0.67 at 18 months (suture out), and 0.78 at 24 months postoperatively. Conclusions: The combination of intraoperative topography and a 24-bite single running suture resulted in a stable astigmatism throughout the follow-up period, even after suture removal. BSCVA reached a 20/40 level as early as 3 months postoperatively and continued to rise after suture removal. The stability of astigmatism and BSCVA shortened the postoperative visual rehabilitation time and provided a high quality of vision early in the postoperative period.

Stromal Opacity After Cross-linking

To the Editor: The same stromal opacities found in the rabbit study by Salomão et al,1 which appeared in the June 2011 issue of the Journal of Refractive Surgery, have been previously described as frequent but asymptomatic complications after corneal cross-linking (CXL) in cases of steep corneas with keratometry values 54.00 diopters (D).2-4 Raiskup et al4 demonstrated that infusion with a hypo-osmolar ribofl avin solution preserved corneal tissue from stromal opacity development even in severe keratoconus cases with ultra-thin corneas, with no reduction of CXL effectiveness. The same phenomenon was observed by our group5 in patients with postoperative LASIK ectasia. Corneas were plumped with hypotonic ribofl avin before CXL irradiation.6 None of the patients developed any stromal opacity, despite their mean central corneal thickness (CCT) was less than the recognized safe cut-off depth of 400 μm. We found that the usual development of deep stromal opacities after CXL was related to a reduction of CCT at 1 month after CXL. Therefore, we decided to study CCT behavior during CXL in 45 corneas with keratoconus. Mean patient age was 27 years (range: 19 to 37 years). After 20 minutes of soaking with 0.1% ribofl avin solution (10 mg ribofl avin5-phosphate in 20% dextran-T-500 10 mL), all corneas with CCT 350 μm were plumped to 400 μm with a hypo-osmolar solution (ribofl avin-5-phosphate) for a mean time of 8 minutes. Intraoperative CCT was measured with ultrasound pachymetry after epithelial removal (t1), after 20 minutes of ribofl avin infusion (t2), after corneal expansion (t3), and at the end of irradiation (t4) (Fig). Posterior stromal opacity formation was evaluated by anterior segment optical coherence tomography up to 12 months postoperatively. No signifi cant difference (P=.003) was found after epithelium removal. A mean CCT reduction of 102.11 μm was measured after 20 minutes of ribofl avin infusion (P .00001). No signifi cant change in CCT was measured at the end of corneal expansion (P=.51) or irradiation (P=.016). Eyes were also divided into 3 groups of 15 eyes each according to preoperative CCT (group I 450 μm, group II between 450 and 500 μm, and group III 500 μm). The decrease in CCT after the fi rst 20 minutes of ribofl avin infusion was signifi cantly higher in group III, with a 28% CCT reduction. Groups I and II showed a 22% and 25% decrease in CCT, respectively. None of the patients presented intraoperative, early, or late postoperative complications such as deep stromal opacities for up to 1 year after CXL. We therefore concluded that CCT reduction during the soaking phase could be a predictive factor for the potential development of stromal opacity after CXL. Because CCT can be measured during the entire CXL procedure, we recommend testing each cornea after the soaking phase and eventually swelling corneas with a CCT 350 μm to avoid stromal scar formation and visual impairment. It is also interesting to note that the thickest corneas thinned at a higher rate than the thinnest, most likely because thick corneas have more interlamellar and interfi brillar spaces and become more dehydrated during the CXL procedure. Paolo Vinciguerra, MD Elena Albè, MD Mario R. Romano, MD, PhD Laura Sabato, MD Silvia Trazza Milan, Italy

Corneal curvature gradient map: a new corneal topography map to predict the corneal healing process.

PURPOSE To evaluate a new curvature gradient topography map to predict postoperative corneal remodeling. METHODS In this retrospective study, 32 eyes of 16 patients with myopia underwent excimer ablation surgery with a postoperative high curvature gradient. The new curvature gradient map (acquired immediately postoperatively) shows the difference between the curvatures of two points over the distance between them; it was compared to the tangential curvature difference map between 1 and 12 months postoperatively to determine their relationship. Corneas were divided into 12 regions for analysis: four 90°-wide sectors centered on 0°, 90°, 180°, and 270°. There were three subdivisions in each sector: central (radius: 0 to 2.75 mm), paracentral (radius: 2.75 to 3.25 mm), and peripheral (radius: 3.25 to 4.5 mm). Linear regression analysis was performed by region. RESULTS The following regions had significant relationships between the initial curvature gradient and curvature difference between 1 and 12 months postoperatively: the paracentral zone of the 90° sector (P = .0145; R(2) = 0.1832) and both the central (P = .0034; R(2) = 0.2522) and paracentral (P = .0452; R(2) = 0.1271) zones of the 270° sector. The greatest average initial tangential curvature was in the 270° sector. CONCLUSIONS The initial curvature gradient after surgery predicted change in tangential curvature over the subsequent 12 months in areas where initial tangential curvature was greatest. When the curvature gradient was high, the surface curvature modification remained in progress months after surgery.

No retinal morphology changes after use of riboflavin and long-wavelength ultraviolet light for treatment of keratoconus

the authors’ informed consent process is that they did not mention disclosure to the patient of the risks associated with LP, nor was there any mention of the presence or absence of complications related to the LP in the Results Section’. We agree with Dr Grzybowski that the article (Ren et al. 2011b) does not contain information whether the patients were informed about the risks associated with a lumbar puncture, nor were potential complications owing to the lumbar puncture mentioned in the article. Thanking Dr Grzybowski for this advice, we hereby state that all patients were informed about the risks related to a lumbar puncture, and it is hereby also stated that none of the patients has been experiencing any complications owing to the lumbar puncture. Thirdly, Dr Grzybowski mentions that ‘While the authors mention an ethical review process, their description lacks sufficient detail to satisfy concerns that adequate attention was paid to protecting patients during their recruitment as research subjects. ...’ The authors would like to turn Dr Grzybowski¢s attention to that they did not consider the study participants as ‘research subjects’ but as patients in need of diagnosis and treatment. In addition, the study had a therapeutic consequence. The results of the study showed that the study participants with a low CSF-P may not receive systemic carbonic anhydrase inhibitors to avoid a further lowering of the CSF-P. Fourthly, Dr Grzybowski finally remarks that ‘There is much concern about ethical issues in the design and conduct of clinical trials in developing countries ..... It was shown in many studies that patients in developing countries can easily be exploited. It was also pointed out that studies in developing countries are more easily carried out because of less stringent controls and restrictions. This should not be a justification for conducting studies in developing countries .....’ Although the statements given by Dr Grzybowski may potentially hold true for some countries, they are not valid for China, where patients have usually been better protected against malpractice by physicians than in other, even higher developed, countries. Perhaps, Dr Grzybowski may never have come to China nor may have had contact with many physicians from China. Dr Grzybowski should understand that in China, after the reform and opening up policy more than 30 years ago, many clinical scientists have become fellows from leading institutions in Europe and the US, and that we have been conducting our research in accordance with international standards [e.g., as shown in the Handan Eye Study (Yang et al. 2011)]. For our study on the potential role of a low CSF-P in the pathogenesis of glaucoma, our work and the study protocol were approved and supervised by The Medical Ethics Committee of Beijing Tongren Hospital, which as a third party was independent of our research team. In addition, the CSF-P in patients with glaucoma has also been examined in other investigations made in Western Europe (Jaggi et al. 2011). In those studies, not only lumbar puncture but also CSF sampling and computer tomographic cisternography including an intrathecal injection of iopamidol were performed (Jaggi et al. 2011). Does Dr Grzybowski measure by different yard sticks? In conclusion, we thank Dr Grzybowski for his letter, and we were very cognizant of his concern. We completely agree with him in his general concerns about the welfare and protection of patients. With respect to the specific points he listed in his letter, we refer to the remarks given above.

Long-term resolution of immunological graft rejection after a dexamethasone intravitreal implant

Purpose: To present the results of the injection of an intravitreal implant of dexamethasone 0.7 mg (DEX 0.7 mg) in 4 patients with an immunologic graft rejection after penetrating keratoplasty. Methods: Two of the patients received DEX 0.7 mg because inflammation and corneal edema not related to endothelial cell loss persisted despite the administration of topical prednisolone acetate, subconjunctival betamethasone, and systemic methylprednisolone. The other 2 cases received DEX 0.7 mg at the time rejection was diagnosed. Results: At 1 and 6 months after implantation, all rejection episodes resolved with improvement in uncorrected and best-corrected visual acuity, restoration of graft transparency, reduction of central corneal thickness, and no significant increase in intraocular pressure. Conclusions: In 4 eyes with an immunologic graft rejection after penetrating keratoplasty, the dexamethasone 0.7 mg intravitreal implant was an effective treatment option, even in cases refractory to standard topical and systemic therapy.