Assessment of the Predictive Ability of Theranostics for Corneal Cross-linking in Treating Keratoconus: A Randomized Clinical Trial.

PURPOSE: To validate the ability of theranostic imaging biomarkers in assessing corneal cross-linking (CXL) efficacy in flattening the maximum keratometry (Kmax) index. DESIGN: Prospective, randomized, multicenter, masked clinical trial (ClinicalTrails.gov identifier, NCT05457647). PARTICIPANTS: Fifty patients with progressive keratoconus. INTERVENTION: Participants were stratified to undergo epithelium-off (25 eyes) and epithelium-on (25 eyes) CXL protocols using an ultraviolet A (UV-A) medical device with theranostic software. The device controlled UV-A light both for performing CXL and assessing the corneal riboflavin concentration (riboflavin score) and treatment effect (theranostic score). A 0.22% riboflavin formulation was applied onto the cornea for 15 minutes and 20 minutes in epithelium-off and epithelium-on protocols, respectively. All eyes underwent 9 minutes of UV-A irradiance at 10 mW/cm2. MAIN OUTCOME MEASURES: The primary outcome measure was validation of the combined use of theranostic imaging biomarkers through measurement of their accuracy (proportion of correctly classified eyes) and precision (positive predictive value) to classify eyes correctly and predict a Kmax flattening at 1 year after CXL. Other outcome measures included change in Kmax, endothelial cell density, uncorrected and corrected distance visual acuity, manifest spherical equivalent refraction and central corneal thickness 1 year after CXL. RESULTS: Accuracy and precision of the theranostic imaging biomarkers in predicting eyes that had >0.1 diopter (D) of Kmax flattening at 1 year were 91% and 95%, respectively. The Kmax value significantly flattened by a median of -1.3 D (IQR, -2.11 to -0.49 D; P < 0.001); both the uncorrected and corrected distance visual acuity improved by a median of -0.1 logarithm of the minimum angle of resolution (logMAR; IQR, -0.3 to 0.0 logMAR [P < 0.001] and -0.2 to 0.0 logMAR [P < 0.001], respectively). No significant changes in endothelial cell density (P = 0.33) or central corneal thickness (P = 0.07) were noted 1 year after surgery. CONCLUSIONS: The study demonstrated the efficacy of integrating theranostics in a UV-A medical device for the precise and predictive treatment of keratoconus with epithelium-off and epithelium-on CXL protocols. Concentration of riboflavin and its UV-A light mediated photoactivation in the cornea are the primary factors determining CXL efficacy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Spatial targeted delivery of riboflavin with a controlled corneal iontophoresis delivery system in theranostic-guided UV-A light photo-therapy.

Seven human donor eye globes underwent corneal cross-linking using theranostic UV-A device with accessory corneal iontophoresis system for patterned delivery of a 0.22% riboflavin solution. Theranostic-guided UV-A light illumination assessed riboflavin distribution and treated corneas at 10 mW/cm2 for 9 min with a 5.0-mm beam size. Corneal topography maps were taken at baseline and 2-h post-treatment. Analysis utilized corneal topography elevation data, with results showing controlled riboflavin delivery led to a consistent gradient, with 40% higher levels centrally (248 ± 79 µg/cm3) than peripherally (180 ± 72 µg/cm3 at ±2.5 mm from the center). Theranostic-guided UV-A light irradiation resulted in significant changes in corneal topography, with a decrease in best-fit sphere value (-0.7 ± 0.2 D; p < 0.001) and consistent downward shift in corneal elevation map (-11.7 ± 3.7 µm). The coefficient of variation was 2.5%, indicating high procedure performance in achieving significant and reliable corneal flattening.

Real-time monitoring of riboflavin concentration using different clinically available ophthalmic formulations for epi-off and epi-on corneal cross-linking.

PURPOSE: To assess the feasibility of theranostics to determine the riboflavin concentration in the cornea using clinically available ophthalmic formulations during epithelium-off (epi-off) and transepithelial (epi-on) corneal cross-linking procedures. METHODS: Thirty-two eye bank human donor corneas were equally randomized in eight groups; groups 1 to 3 and groups 4 to 8 underwent epi-off and epi-on delivery of riboflavin respectively. Riboflavin ophthalmic solutions were applied onto the cornea according to the manufacturers' instructions. The amount of riboflavin into the cornea was estimated, at preset time intervals during imbibition time, using theranostic UV-A device (C4V CHROMO4VIS, Regensight srl, Italy) and expressed as riboflavin score (d.u.). Measurements of corneal riboflavin concentration (expressed as µg/cm3) were also performed by spectroscopy absorbance technique (AvaLight-DH-S-BAL, Avantes) for external validation of theranostic measurements. RESULTS: At the end of imbibition time in epi-off delivery protocols, the average riboflavin score ranged from 0.77 ± 0.38 (the average corneal riboflavin concentration was 213 ± 190 µg/cm3) to 1.79 ± 0.07 (554 ± 103 µg/cm3). In epi-on delivery protocols, the average riboflavin score ranged from 0.17 ± 0.01 to 0.67 ± 0.19 (corneal riboflavin concentration ranged from 6 ± 5 µg/cm3 to 122 ± 39 µg/cm3) at the end of imbibition time. A statistically significant linear correlation (P ≤ 0.05) was found between the theranostic and spectrophotometry measurements in all groups. CONCLUSIONS: Real-time theranostic imaging provided an accurate strategy for assessing permeation of riboflavin into the human cornea during the imbibition phase of corneal cross-linking, regardless of delivery protocol. A large variability in corneal riboflavin concentration exists between clinically available ophthalmic formulations both in epi-off and epi-on delivery protocols.

Predicting corneal cross-linking treatment efficacy with real-time assessment of corneal riboflavin concentration.

PURPOSE: To assess predictability of tissue biomechanical stiffening induced by UV-A light-mediated real-time assessment of riboflavin concentration during corneal crosslinking (CXL) of human donor tissues. SETTING: Studio Italiano di Oftalmologia, Rome, Italy. DESIGN: Laboratory study. METHODS: 20 sclerocorneal tissues were randomly stratified to undergo CXL with either the epithelium intact (n = 12) or removed (n = 8). Samples underwent corneal soaking with 0.22% riboflavin formulation (RitSight) with dosing time of t = 10 minutes and t = 20 minutes in epithelium-off and epithelium-on protocols, respectively. All tissues underwent 9-minute UV-A irradiance at 10 mW/cm 2 using theranostic device (C4V CHROMO4VIS). The device used controlled UV-A light irradiation to induce both imaging and treatment of the cornea, providing a real-time measure of corneal riboflavin concentration and treatment efficacy (ie, theranostic score) during surgery. Tissue biomechanics were assessed with an air-puff device (Corvis), which was performed before and after treatment. A 3-element viscoelastic model was developed to fit the corneal deformation response to air-puff excitation and to calculate the mean corneal stiffness parameter (k c ). RESULTS: Significant corneal tissue stiffening ( P < .05) was induced by the theranostic UV-A device in either CXL treatment protocol. Significant correlation was found between the theranostic score and the increase in k c ( R = 0.75; P = .003). The score showed high accuracy (94%) and precision (94%) to predict correctly samples that had improved tissue biomechanical strengthening. CONCLUSIONS: Real-time assessment of corneal riboflavin concentration provided a predictive and precise approach for significant improvement of tissue strength on individual corneas, regardless of CXL treatment protocol.

A randomized clinical trial assessing theranostic-guided corneal cross-linking for treating keratoconus: the ARGO protocol.

The Assessment of theranostic guided riboflavin/UV-A corneal cross-linking for treatment of keratoconus (ARGO; registration number NCT05457647) clinical trial tests the hypothesis that theranostic-guided riboflavin/UV-A corneal cross-linking (CXL) can provide predictable clinical efficacy for halting keratoconus progression, regardless of treatment protocol, i.e., either with or without epithelial removal. Theranostics is an emerging therapeutic paradigm of personalized and precision medicine that enables real-time monitoring of image-guided therapy. In this trial, the theranostic software module of a novel UV-A medical device will be validated in order to confirm its accuracy in estimating corneal cross-linking efficacy in real time. During CXL procedure, the theranostic UV-A medical device will provide the operator with an imaging biomarker, i.e., the theranostic score, which is calculated by non-invasive measurement of corneal riboflavin concentration and its UV-A light mediated photo-degradation. ARGO is a randomized multicenter clinical trial in patients aged between 18 and 40 years with progressive keratoconus aiming to validate the theranostic score by assessing the change of the maximum keratometry point value at 1-year postoperatively. A total of 50 participants will be stratified with allocation ratio 1:1 using a computer-generated stratification plan with blocks in two treatment protocols, such as epithelium-off or epithelium-on CXL. Following treatment, participants will be monitored for 12 months. Assessment of safety and performance of theranostic-guided corneal cross-linking treatment modality will be determined objectively by corneal tomography, corneal endothelial microscopy, visual acuity testing and slit-lamp eye examination.

Theranostic-guided corneal cross-linking: Preclinical evidence on a new treatment paradigm for keratoconus.

Theranostics is an emerging therapeutic paradigm of personalized medicine; the term refers to the simultaneous integration of therapy and diagnostics. In this work, theranostic-guided corneal cross-linking was performed on 10 human sclero-corneal tissues. The samples were soaked with 0.22% riboflavin formulation and underwent 9 minutes UV-A irradiance at 10 mW/cm2 using theranostic device, which provided both a measure of corneal riboflavin concentration and a theranostic score estimating treatment efficacy in real time. A three-element viscoelastic model was developed to fit the deformation response of the cornea to air-puff excitation of dynamic tonometry and to calculate the mean corneal stiffness parameter before and after treatment. Significant correlation was found between the theranostic score and the increase in mean corneal stiffness (R = 0.80; P < .001). Accuracy and precision of the theranostic score in predicting the induced corneal tissue stiffening were both 90%. The riboflavin concentration prior to starting the UV-A photo-therapy phase was the most important variable to allow corneal cross-linking to be effective. Theranostic UV-A light mediated imaging and therapy enables the operator to adopt a precise approach for achieving highly predictable biomechanical strengthening on individual corneas.

Challenges in Age-Related Macular Degeneration: From Risk Factors to Novel Diagnostics and Prevention Strategies.

Age-related macular degeneration (AMD) is a chronic multifactorial eye disease representing the primary cause of vision loss in people aged 60 years and older. The etiopathogenesis of the disease remains uncertain, with several risk factors contributing to its onset and progression, such as genotype, aging, hypertension, smoking, overweight, and low dietary intake of carotenoids. Since the aging populations of the industrialized world are increasing rapidly, the impact of AMD in the socio-economical life-developed countries is expected to increase dramatically in the next years. In this context, the benefits of prevention and early disease detection for prompt and effective treatment can be enormous to reduce the social and economic burden of AMD. Nutritional and lifestyle changes, including dietary intake of xanthophyll pigments, such as lutein and zeaxanthin, no smoking, and regular exercise, are known to protect from risk of AMD progression from early to advanced disease stages. In this review, we present the clinical outcomes of a pilot study on trans-scleral iontophoresis delivery of lutein in patients with AMD. Topical delivery of lutein directly to the macula may provide a more efficient method for enriching the macular pigment and for achieving greater patient compliance to therapy than oral administration and thus enhancing prevention strategies. Modern diagnostic methodologies shall address the major problem of accurately detecting the risk of transition from intermediate AMD to advanced AMD stages. Adaptive optics retinal imaging and resonance Raman spectroscopy are two highly promising technologies for the objective assessment of patients with AMD. In this review, we present some of their clinical applications for collecting quantitative measurements of retinal cellular changes and macular content of xanthophyll pigments, respectively. In conclusion, there is great expectation that technological advancements in AMD management will deliver improved screening, therapeutic prevention, and diagnostic systems in the coming decade through a pro-active strategy of "treatment for prevention" that will aim to reduce the global burden of vision loss caused by AMD in the elderly.

Adverse events after riboflavin/UV-A corneal cross-linking: a literature review.

BACKGROUND: Riboflavin/UV-A corneal cross-linking (CXL) for treating keratoconus and iatrogenic corneal ectasia has been well-established as first treatment option to stabilize corneal tissue biomechanical instability. Although the plethora of clinical studies has been published into the field, there is no systematic review assessing the type and frequency of adverse events after CXL. METHODS: A systemic literature review on clinical safety and adverse events after CXL in patients with keratoconus and corneal ectasia was performed using PubMed. A literature search was performed for relevant peer-reviewed publications. The main outcome measures extracted from the articles were adverse events, endothelial cell density, corrected distance visual acuity and maximum simulated keratometry. RESULTS: The most frequent adverse events after CXL were corneal haze and corneal edema, which were mild and transient. The severe adverse events were infrequent (cumulative incidence: < 1.3%) after CXL. The clinical benefits of CXL highly outweighed the risks for the treatment of keratoconus and corneal ectasia. CONCLUSIONS: The severe adverse events with permanent sequelae are infrequent after CXL and all are associated with corneal de-epithelialization, such as infectious keratitis and corneal scarring.

Comparison between standard and transepithelial corneal crosslinking using a theranostic UV-A device.

PURPOSE: To assess corneal concentration of riboflavin in two different corneal crosslinking protocols performed by a novel image-guided therapeutic (or "theranostic") UV-A device. METHODS: Ten human eye bank donor tissues were used in this work. The tissues underwent corneal cross-linking according to the conventional treatment protocol (n = 5; 30 min of stromal soaking followed by 30 min of 3 mW/cm2 UV-A irradiance) and the iontophoresis-assisted transepithelial protocol (n = 5; soaking for 5 min at 1 mA/min and 9 min of 10 mW/cm2 UV-A irradiance) using a theranostic UV-A device (Vision Engineering Italy srl, Italy). The device provided real time assessment of riboflavin concentration by hyperspectral image analysis of the cornea. A 0.1% riboflavin hypotonic solution (Ricrolin+, Sooft Italia Spa, Italy) was used in all cases. RESULTS: Manual application of hypotonic riboflavin for 30 min into the stroma achieved greater corneal riboflavin concentration (425 ± 77 µg/cm3) than transepithelial delivery of riboflavin by corneal iontophoresis (195 ± 35 µg/cm3; P = 0.001). In both UV-A irradiation protocols, corneal riboflavin concentration decreased exponentially with a constant energy rate of 2.3 ± 0.5 J/cm2 and 1.8 ± 0.3 J/cm2 respectively. At the end of treatment, the average corneal concentration of riboflavin decreased by ≥ 85%, with values of 54 ± 29 µg/cm3 and 31 ± 9 µg/cm3 (P = 0.11), respectively. CONCLUSION: Manual application of riboflavin onto the stroma achieved almost 50% greater concentration of riboflavin than transepithelial delivery by corneal iontophoresis. The theranostic UV-A device provided a novel approach to estimate corneal concentration of riboflavin non-invasively during treatment.

Role of corneal epithelial thickness mapping in the evaluation of keratoconus.

PURPOSE: To investigate the corneal epithelial thickness profiles in patients with a confirmed diagnosis of stable and progressive keratoconus. SETTING: Studio Italiano di Oftalmologia, Rome, Italy. DESIGN: Observational study. METHODS: 86 patients with either stable (n = 52) or progressive (n = 34) keratoconus and 182 healthy controls were enrolled in the study. Disease progression was confirmed by repeated corneal topographies over 1 year follow-up before inclusion in the study. All subjects had full corneal and epithelial thickness mapping taken by spectral domain optical coherence tomography (SD-OCT). The full corneal mapping was investigated by evaluating the central corneal thickness, the thinnest point, the superonasal-inferotemporal thickness difference and the minimum-median thickness difference. The epithelial mapping was investigated by assessing the 2 mm central thickness, the inferior paracentral (2-5 mm) thickness, and the minimum-maximum thickness difference. RESULTS: No significant differences in full corneal mapping were found between stable and progressive keratoconic eyes. Of note, the inferior paracentral region of the corneal epithelium was significantly thinner in progressive (50 ± 3 µm) than stable (53 ± 4 µm) keratoconus (P < 0.001). CONCLUSIONS: The SD-OCT corneal epithelial mapping was valuable for detecting local thickness changes in eyes with keratoconus. Monitoring the corneal epithelial changes across the inferior area in patients with keratoconus could be worthy for assessing disease progression.

Two-year outcomes of a randomized controlled trial of transepithelial corneal crosslinking with iontophoresis for keratoconus.

PURPOSE: To evaluate the 2-year clinical outcomes of corneal crosslinking (CXL) using transepithelial iontophoresis CXL (T-ionto CXL) in comparison with standard CXL for the treatment of progressive keratoconus. SETTING: Single-site study. DESIGN: Randomized controlled clinical trial with identifier code NCT02117999. METHODS: The eyes of the participants were randomized to have either T-ionto CXL and/or standard CXL. Assessments of uncorrected (UDVA) and corrected (CDVA) distance visual acuities (logarithm of the minimum angle of resolution [logMAR]), manifest refraction spherical equivalent, maximum simulated keratometry (K) (diopters [D]), corneal higher-order aberrations (HOAs), central corneal thickness (CCT), and endothelial cell density (ECD) were performed at 3 days, 7 days, and 1, 3, 6, 12, and 24 months postoperatively. RESULTS: The study comprised 34 eyes (25 patients). There were 22 eyes in the T-ionto CXL group and 12 eyes in the standard CXL group. Two years after T-ionto CXL and standard CXL, the mean maximum K flattened by -1.05 ± 1.20 D (P = .07) (20 eyes) and -1.51 ± .89 D (P < .001) (11 eyes), respectively. Two study cases (10%) and no control showed maximum K steepening of more than 1.0 D at 24 months postoperatively. The mean change in CDVA was -0.08 ± 0.15 logMAR (P = .04) and -0.02 ± 0.06 logMAR (P = .34) after T-ionto CXL and standard CXL, respectively. A significant average decrease in the myopic defocus (+0.81 D; P < .05) was found in both groups. No significant differences in the outcome measures between treatments were found at 24 months. The corneal HOAs, CCT, and ECD values did not change significantly in any group at 2 years postoperatively. CONCLUSIONS: Clinically significant topographic, visual, and refractive improvements were found 2 years after T-ionto CXL; standard CXL showed more significant corneal apex flattening than the transepithelial iontophoresis protocol.

Assessment of stromal riboflavin concentration-depth profile in nanotechnology-based transepithelial corneal crosslinking.

PURPOSE: To determine the intrastromal concentration of riboflavin in nanotechnology-based transepithelial corneal crosslinking. SETTING: Consiglio Nazionale delle Ricerche, Messina, Italy. DESIGN: Experimental study. METHODS: Six human donor sclerocorneal tissues were used to evaluate penetration of nanotechnology-based riboflavin 0.1% solution in the stroma through the intact epithelium. Three additional tissues were deepithelialized and soaked with dextran 20.0%-enriched riboflavin 0.1% solution for 30 minutes. After corneal soaking with riboflavin, all tissues were irradiated using a 10 mW/cm2 device for 9 minutes. Two-photon emission fluorescence (TPEF) axial scanning measurements were collected in all specimens before treatment and immediately after corneal soaking with riboflavin and ultraviolet-A (UVA) irradiation of the cornea. The absorbance spectra of each tissue were collected at the same time intervals. The TPEF signals and absorbance spectra were used to calculate the concentration-depth profile of riboflavin in the corneal stroma during treatments. RESULTS: The mean stromal riboflavin concentration was 0.008% ± 0.003% (SD) and 0.017% ± 0.001% after transepithelial soaking with the nanotechnology-based solution and standard soaking, respectively (P = .001). After UVA irradiation of the cornea, the mean consumption of riboflavin was 52% ± 13% and 67% ± 2% in the study group and control group, respectively (P < .01). CONCLUSIONS: The nanotechnology-based platform was effective in enriching the anterior stroma with riboflavin through the intact epithelium, although the riboflavin concentration-depth profile rapidly decreased across the mid and posterior stroma. The treatment-induced stiffening effect on the corneal stroma was not assessed in this study.

New technique for femtosecond laser creation of clear corneal incisions for cataract surgery.

PURPOSE: To evaluate the changes in corneal topography and corneal higher-order wavefront aberrations with the use of a new technique in which clear corneal incisions (CCIs) for cataract surgery are created with a femtosecond laser. SETTING: IRCCS Fondazione G.B. Bietti, Rome, Italy. DESIGN: Prospective randomized case series. METHODS: Cataract surgery patients were randomized into 2 groups. In the study group, a 3-plane CCI was created with a femtosecond laser. In the control group, the single plane-angled CCI was created manually using disposable knives. Simulated keratometry (K) values and corneal higher-order wavefront aberrations with 3.5 mm and 6.0 mm pupils were compared between groups. RESULTS: Each group comprised 10 eyes. At 6 months, the mean change in K values from preoperatively was 0.16 diopter (D) ± 0.14 (SD) in the study group and 0.34 ± 0.16 D in the control group, with no differences between groups (P > .05). The manual CCI significantly increased corneal higher-order wavefront aberrations with 3.5 mm and 6.0 mm pupils (both P < .05). In the study group, corneal higher-order wavefront aberrations increased significantly with a 6.0 mm pupil only (P ≤ .02). The induced changes in corneal higher-order wavefront aberrations were significantly different between groups over both pupil sizes (P < .05). CONCLUSIONS: The femtosecond laser-created CCI did not induce significant changes in simulated K or corneal higher-order wavefront aberrations over the mesopic pupil size. The lower amount of induced corneal higher-order wavefront aberrations with the new technique than with manual CCI could be related to the different geometry of the 2 techniques.

Randomized Controlled Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis with the Dresden Protocol in Progressive Keratoconus.

PURPOSE: To compare clinical outcomes of transepithelial corneal cross-linking using iontophoresis (T-ionto CL) and standard corneal cross-linking (standard CL) for the treatment of progressive keratoconus 12 months after the operation. DESIGN: Prospective randomized controlled clinical trial. PARTICIPANTS: Thirty-four eyes of 25 participants with progressive keratoconus were randomized into T-ionto CL (22 eyes) or standard CL (12 eyes). METHODS: T-ionto CL was performed using an iontophoresis device with dextran-free 0.1% riboflavin-5-phosphate solution with enhancers and by irradiating the cornea with a 10 mW/cm2 ultraviolet A device for 9 minutes. Standard CL was performed according to the Dresden protocol. MAIN OUTCOME MEASURES: The primary outcome measure was stabilization of keratoconus after 12 months through analysis of maximum simulated keratometry readings (Kmax, diopters). Other outcome measures were corrected distance visual acuity (CDVA, logarithm of the minimum angle of resolution [logMAR]), manifest spherical equivalent refraction (D), central corneal thickness (CCT, micrometers) and endothelial cell density (ECD). Follow-up examinations were arranged at 3 and 7 days and 1, 3, 6, and 12 months. RESULTS: Twelve months after T-ionto CL and standard CL, Kmax on average flattened by -0.52±1.30 D (P = 0.06) and -0.82±1.20 D (P = 0.04), respectively. The mean change in CDVA was -0.10±0.12 logMAR (P = 0.003) and -0.03±0.06 logMAR (P = 0.10) after T-ionto CL and standard CL, respectively. The manifest spherical equivalent refraction changed on average by +0.71±1.44 D (P = 0.03) and +0.21±0.76 D (P = 0.38), respectively. The CCT and ECD measures did not change significantly in any group at 12 months. Significant differences in the outcome measures between treatments were found in the first week postoperatively. No complications occurred in the T-ionto CL group; 1 eye (8%) had sterile corneal infiltrates, which did not affect the final visual acuity, in the standard CL group. CONCLUSIONS: Significant visual and refractive improvements were found 12 months after T-ionto CL, though the average improvement in corneal topography readings was slightly lower than the Dresden protocol in the same period.

Agreement Between Predicted and Measured Ablation Depth After Femtosecond Laser-Assisted LASIK for Myopia.

PURPOSE: To investigate agreement between the predicted ablation depth calculated by the EX500 excimer laser (Wavelight Laser Technologie AG, Erlangen, Germany) and the measured ablation depth in eyes that have undergone femtosecond laser-assisted LASIK (FS-LASIK) for myopia. METHODS: Corneal thickness was measured with a rotating Scheimpflug camera preoperatively and 3 months postoperatively and the difference between these values was defined as the measured ablation depth. The difference between the predicted and the measured ablation depth was defined as the difference in ablation depth (ΔAD). RESULTS: In 85 eyes of 85 patients, no statistically significant difference was detected between the mean predicted ablation depth (66.33 ± 24.15 µm) and the measured ablation depth at the thinnest corneal location (67.04 ± 30.94 µm), the corneal apex (67.52 ± 31.22 µm), or the pupil center (67.73 ± 31.48 µm). Bland-Altman plots revealed moderate agreement for measurements at the thinnest point (95% limits of agreement [LoA]: -25.13 to 23.70 µm), corneal apex (95% LoA: -24.70 to 22.33 µm), and pupil center (95% LoA: -25.30 to 22.51 µm), with a proportional bias between the average ablation depth and ΔAD. The predicted ablation depth was overestimated in eyes with lower correction and underestimated in eyes with higher correction. CONCLUSIONS: Moderate agreement between the predicted and measured ablation depth warrants caution when planning myopic FS-LASIK and calculating the residual bed thickness and percent tissue altered. When higher amounts of correction are planned, the laser software may underestimate the predicted ablation depth.

Influence of the effective lens position, as predicted by axial length and keratometry, on the near add power of multifocal intraocular lenses.

PURPOSE: To calculate the near focal distance of different multifocal intraocular lenses (IOLs) as a function of the 2 parameters that are measured before cataract surgery; that is, axial length (AL) and refractive corneal power (keratometry [K]). SETTING: GB Bietti Foundation IRCCS, Rome, Italy. DESIGN: Noninterventional theoretical study. METHODS: The IOL power for emmetropia was first calculated in an eye model with the AL ranging from 20 to 30 mm and K from 38 to 48 diopters (D). Then, the predicted myopic refraction for any given IOL add power (from +1.5 to +4.0 D) was calculated, and from this value the near focal distance was obtained. Calculations were also performed for the average eye (K = 43.81 D; AL = 23.65 mm). RESULTS: The near focal distance increased with increasing values of K and AL for each near power add. The near focal distance ranged between 53 cm and 72 cm (21 inches and 28 inches) for a multifocal IOL with +2.50 D, between 44 cm and 60 cm (17 inches and 24 inches) for a multifocal IOL with +3.00 D add, and between 33 cm and 44 cm (13 inches and 18 inches) for a multifocal IOL with +4.00 D add. In the average eye, the near focal distance ranges between 36 cm (near add power = 4.00 D) and 99 cm (near add power = 1.5 D). CONCLUSIONS: Longer eyes with steeper corneas showed the longest near focal distance and could experience more difficulties in focusing near objects after surgery. The opposite was true for short hyperopic eyes. FINANCIAL DISCLOSURE: Dr. Hoffer receives licensing fees for the commercial use of the registered trademark Hoffer from all biometry manufacturers using the Hoffer Q formula to ensure that it is programmed correctly and book royalties from Slack, Inc., for the textbook IOL Power. None of the authors has a financial or proprietary interest in any material or method mentioned.

Objective Monitoring of Corneal Backward Light Scattering After Femtosecond Laser-assisted LASIK.

PURPOSE: To investigate the changes in corneal backward light scattering, as measured by a rotating Scheimpflug camera with automated corneal densitometry software, in eyes treated with femtosecond laser-assisted LASIK (FS-LASIK). METHODS: The cornea was examined preoperatively and postoperatively at 1 day, 1 week, and 1, 3, and 6 months in 23 patients who underwent myopic FS-LASIK. Local analysis of corneal backscatter was performed on four concentric radial zones across a 12-mm diameter (0 to 2, 2 to 6, 6 to 10, and 10 to 12 mm) and at a different corneal depth (anterior 120 µm, central and posterior 60 µm). RESULTS: A statistically significant increase in corneal backward light scattering (P < .0001) was detected within the central 10 mm of the anterior cornea. The increase in corneal densitometry was gradually reversed over 6 months. The difference compared to preoperative values was no longer statistically significant at 3 and 6 months after surgery in the central cornea, whereas it remained significant in the mid-peripheral annulus (ranging from 6 to 10 mm), where the flap edge was located. CONCLUSIONS: FS-LASIK is followed by an increase in corneal backward light scattering during the early postoperative period that returns to baseline by 3 months. Whereas the increase in corneal densitometry at the flap edge location can be related to a scarring reaction, the explanation for such an increase in the central anterior cornea remains speculative.

HIGH-RESOLUTION MULTIMODAL IMAGING AFTER IDIOPATHIC EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To investigate the changes of the vitreomacular interface during a 1-year follow-up after idiopathic epiretinal membrane (iERM) surgery. METHODS: Six patients affected by fovea-attached iERM were recruited in this pilot study. Pars plana vitrectomy associated with epiretinal membrane peeling was performed uneventfully in all cases. In four cases, the inner limiting membrane was removed using Brilliant blue G. En face high-resolution adaptive optics and cross-sectional spectral domain optical coherence tomography retinal imaging were performed before and at 1, 3, 6, and 12 months after surgery. The microstructures of vitreomacular interface in high-resolution adaptive optics images were correlated to the cross-sectional spectral domain optical coherence tomography data. RESULTS: Preoperatively, adaptive optics images showed multiple abnormalities of the vitreomacular interface, such as macrofolds, microfolds, and hyperreflective microstructures. We identified two subtypes of iERM according to the distribution of microfolds over the foveal area, which included the radial-type and the grid-type iERM. After surgery, the morphology of the vitreomacular interface changed compared with the preoperative state. The number of both macrofolds and microfolds was reduced in all cases. The hyperreflective structures were still resolvable in all cases, however presenting different shape and morphology than preoperatively. In addition, they showed marked differences between eyes that had internal limiting membrane removal and eyes that did not. CONCLUSION: Adaptive optics imaging gives new insight into the changes of vitreomacular interface after iERM surgery. Enhanced multimodal imaging of the vitreomacular interface and retinal structures can be valuable to monitor treatment outcome of iERM.

Ultraviolet A: Visible spectral absorbance of the human cornea after transepithelial soaking with dextran-enriched and dextran-free riboflavin 0.1% ophthalmic solutions.

PURPOSE: To evaluate the stromal concentration of 2 commercially available transepithelial riboflavin 0.1% solutions in human donor corneas with the use of spectrophotometry. SETTING: University of Calabria, Rende, Italy. DESIGN: Experimental study. METHODS: The absorbance spectra of 12 corneal tissues were measured in the 330 to 700 nm wavelength range using a purpose-designed spectrophotometry setup before and after transepithelial corneal soaking with a 15% dextran-enriched riboflavin 0.1% solution (n = 6) or a hypotonic dextran-free riboflavin 0.1% solution (n = 6). Both ophthalmic solutions contained ethylenediaminetetraacetic acid and trometamol as enhancers. In addition, 4 deepithelialized corneal tissues underwent stromal soaking with a 20% dextran-enriched riboflavin 0.1% solution and were used as controls. All the riboflavin solutions were applied topically for 30 minutes. The stromal concentration of riboflavin was quantified by analysis of absorbance spectra of the cornea collected before and after application of each solution. RESULTS: The mean stromal riboflavin concentration was 0.012% ± 0.003% (SD), 0.0005% ± 0.0003% (P < .001), and 0.004% ± 0.001% (P < .01) in tissues soaked with 20% dextran-enriched, 15% dextran-enriched, and hypotonic dextran-free solutions, respectively. The difference of stromal riboflavin concentration between the 2 transepithelial solutions was statistically significant (P < .01). CONCLUSIONS: Dextran-enriched solutions required complete corneal deepithelialization to permit effective stromal soaking with riboflavin. Nevertheless, riboflavin in hypotonic dextran-free solution with enhancers permeates across stroma through an intact epithelium. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.