Intereye Asymmetry as a Predictor of Progression in Patients With Untreated Keratoconus: Findings From a Longitudinal Study.

PURPOSE: The purpose of this study was to evaluate interocular predictors of progression in patients with untreated keratoconus. METHODS: This is a multicenter longitudinal observational study with real-world data collected through the Save Sight Keratoconus Registry. Patients between the period of June 2000 and September 2022 were included in this study. Parameters such as patient age, sex, ocular history, visual acuity, K2, Max-K, and thinnest corneal thickness pachymetry (TCT) were analyzed. RESULTS: There were 4342 untreated eyes from 2171 patients with keratoconus. A total of 333 patients showed progression of either Max-K, TCT, or both, whereas 1838 patients showed stable parameters. Factors associated with a higher incidence of progression in Max-K were younger baseline age (HR 0.96 per year older; 95% CI 0.95-0.98, P < 0.0001) and a higher baseline intereye asymmetry in Max-K (HR 1.02 per higher diopter; 95% CI 1.00-1.04, P = 0.04). A younger baseline age was the only predictor of progression in TCT (HR 0.97 per year older; 95% CI 0.95-0.99, P = 0.001). CONCLUSIONS: Age is the most significant predictor of progression for both corneal thinning and progression of Max-K. Interocular asymmetry in Max-K at baseline could be used as part of an algorithm for determining the risk of keratoconus progression. It is recommended that patients with higher interocular asymmetry in Max-K have a closer follow-up of both eyes as they are at a higher risk of progression.

Herpes Zoster Ophthalmicus: Presentation, Complications, Treatment, and Prevention.

Herpes zoster (HZ) is caused by reactivation of latent infection of varicella zoster virus (VZV) in sensory (cranial, dorsal root) ganglia. Major risk factors for HZ are increasing age and immunosuppression. HZ ophthalmicus (HZO) is a subset of HZ with involvement of the ophthalmic division of the fifth cranial trigeminal nerve. Approximately 4-20% of patients with HZ develop HZO. Approximately 50% of patients with HZO develop ocular disease, among whom up to 25% develop chronic or recurrent disease. Common manifestations of ocular disease include conjunctivitis, keratitis, and uveitis, whereas optic neuropathy and retinitis are uncommon. Due to the potential for vision impairment, ocular involvement requires urgent ophthalmic consultation. Early recognition and timely treatment with antivirals may prevent ocular complications. HZO is preventable by vaccination against HZ. Vaccine efficacy/effectiveness studies have been largely conducted for HZ with few studies assessing HZO. Both the recombinant adjuvanted vaccine (RZV) and live-attenuated vaccine (ZVL) significantly reduce the incidence of HZ and HZO in older adults. RZV is more effective than ZVL. Data on the effectiveness of vaccines for prevention of recurrent disease in patients with HZO are limited; however, vaccination is recommended. Despite recommendations to vaccinate individuals likely to benefit from an HZ vaccine, coverage for adults remains suboptimal. Barriers to vaccination include patient beliefs about HZ or HZ vaccines, and factors related to healthcare providers. In particular, the lack of a recommendation from their primary care physician is often cited by patients as a reason for remaining unvaccinated. By encouraging vaccination against HZ, physicians not only prevent HZ and HZO but also potential vision loss due to HZO.Graphical abstract available for this article.

Shingles, also known as herpes zoster, is a common and painful rash that develops when the virus that causes chickenpox in children reactivates, most often in adults. When shingles affects the eye or the area surrounding the eye, it is called herpes zoster ophthalmicus, or HZO for short. Up to one-fifth of people with shingles have HZO, and this risk increases with age and in people with other conditions that affect their immune system. Common signs and symptoms include a rash on the face, pain, fever, and headache, as well as symptoms in the eye, such as discomfort, redness, and discharge. HZO has the potential to cause permanent vision loss, and because of this, it is important that people with symptoms are referred to an eye doctor ("ophthalmologist") as soon as possible. Early diagnosis of HZO is essential for effective treatment and prevention of the more serious complications it can cause. Treatment within 3 days of the symptoms occurring, with medications known as antivirals, can shorten the duration of a shingles episode and help relieve the pain. To help prevent the risk of shingles and its subtypes like HZO, vaccination is recommended. Two vaccines are currently approved for the prevention of shingles in adults. Although these vaccinations are recommended, some people do not have them for various reasons, which include their own personal beliefs about vaccinations or that their doctor has not recommended it to them. It is important that vaccinations against shingles are recommended to all patients eligible to receive one.

Systemic treatment and surgical intervention in inflammatory Terrien disease.

This case report presents a unique instance of a 55-year-old male patient exhibiting features of both Terrien marginal degeneration (TMD) and Fuchs' superficial marginal keratitis. Characterized by peripheral corneal thinning vascularization, and a pseudopterygium, the patient experienced recurrent photophobia, redness, and tearing over 15 years. This case challenges the traditional distinction between TMD and Fuchs' superficial marginal keratitis, suggesting a potential common underlying disorder. Mycophenolate mofetil provided a partial response, while pseudopterygium removal led to sustained remission, emphasizing its therapeutic significance. This case highlights the first documented use of mycophenolate in TMD and supports the notion of shared vasculitic origins between TMD and Fuchs' keratitis, raising intriguing questions about targeted therapeutic interventions.

Influence of Keratoconus Severity on Detecting True Progression with Scheimpflug Imaging and Anterior Segment Optical Coherence Tomography.

To determine consistent change over time in keratoconus disease, it is necessary to establish progression cut-off values based on intersession variability of the device used to monitor the cornea. The aim of this study was to analyze the accuracy of corneal parameters using Scheimpflug tomography and anterior segment optical coherence tomography in healthy and keratoconic eyes of varying severity to determine the cut-off values that indicate real progression. Three repeated measurements of each cornea of healthy (20 eyes) and keratoconic eyes (mild = 16, moderate = 25 and severe = 20) were recorded using Pentacam and Casia SS-1000 devices, which were repeated 2-3 weeks later. K1, K2, maximal anterior and posterior keratometry, and corneal thickness at the thinnest location (TCT) were collected. The accuracy was excellent with both devices; however, the Casia device presented better repeatability and reproducibility in all parameters in all groups compared to the Pentacam. The cut-off of the Pentacam and Casia in the mild stage were lower (K1 = 0.50 and 0.37 D; K2 = 0.51 and 0.37 D; Kmax-A = 1.24 and 0.65 D; Kmax-P = 0.38 and 0.17 D; TCT = 19.64 and 11.19 µm) than that of the severe stage (K1 = 1.09 and 0.88 D; K2 = 1.41 and 0.87 D; Kmax-A = 2.74 and 2.15 D; Kmax-P = 0.82 and 0.22 D; TCT = 28.68 and 14.83 µm). These results show that the greater the keratoconus severity, the greater the change that must occur for it to be considered real.

Detecting True Change in Keratoconus after Intracorneal Ring Segment Implantation.

Confirming the progression of keratoconus is of paramount relevance to providing the appropriate treatment. Real change should be considered consistent over time. It must be greater than the variability of the measurement of the device used to monitor the cornea. The present study aimed to assess the intraobserver repeatability and intersession reproducibility of a Scheimpflug camera in measuring corneal parameters in virgin keratoconus and intrastromal corneal ring segments (ICRS) implantation eyes to discriminate real change from measurement noise. Sixty keratoconus and 30 ICRS eyes were included. Corneal parameters were determined in three consecutive measurements and were repeated 2 weeks later. The precision within the same session for all parameters was better in the keratoconic eyes, with mean repeatability limits 33% narrower (range 13% to 55%) compared with ICRS eyes. Mean reproducibility limits were 16% narrower (range +48% to -45%) compared with ICRS eyes. The cutoff values to consider a real corneal shape change were lower for virgin keratoconic than for ICRS, except for the thinnest corneal thickness and Stage C (ABCD system), which were the opposite. Corneal tomography measurements in ICRS eyes showed worse accuracy than in virgin keratoconus, which should be taken into account by practitioners in patients' follow up.

Derivation of Limbal Stem Cells from Human Adult Mesenchymal Stem Cells for the Treatment of Limbal Stem Cell Deficiency.

Approximately 10 million individuals have blindness due to limbal stem cell (LSCs) deficiency, one of the most challenging problems in ophthalmology. To replenish the LSC pool, an autologous extraocular cell source is appropriate, thereby avoiding the risk of immune rejection, the need for immunosuppression and the risk of damaging the contralateral eye. In recent years, adipose-derived mesenchymal stem cells (ADSCs) have been a key element in ocular regenerative medicine. In this study, we developed a protocol for deriving human LSCs from ADSCs compatible with the standard carrier human amniotic membrane, helping provide a stem cell pool capable of maintaining proper corneal epithelial homeostasis. The best protocol included an ectodermal induction step by culturing ADSCs with media containing fetal bovine serum, transforming growth factor-ß inhibitor SB-505124, Wnt inhibitor IWP-2 and FGF2 for 7 days, followed by an LSC induction step of culture in modified supplemental hormonal epithelial medium supplemented with pigment epithelium-derived factor and keratinocyte growth factor for 10 additional days. The optimal differentiation efficiency was achieved when cells were cultured in this manner over vitronectin coating, resulting in up to 50% double-positive αp63/BMI-1 cells. The results of this project will benefit patients with LSC deficiency, aiding the restoration of vision.

Five-year corneal cross-linking outcomes: A Save Sight Keratoconus Registry Study.

BACKGROUND: We aimed to determine the long-term outcomes of epithelium-off cross-linking (CXL) in keratoconus patients. METHODS: An observational registry study from 41 centres across 5 countries was carried out. Primary outcomes included the mean change in visual acuity (VA), Kmax, K2, and thinnest corneal thickness (TCT) at 1-5 years. Secondary outcomes included the percentage of eyes with worsening, stable and improving outcomes. RESULTS: There were 976 eyes of 794 patients with 1-year of complete follow-up, 501 eyes with 2-years, 355 with 3-years, 235 with 4-years and 162 with 5-years. There was a significant improvement in mean VA from baseline by 3.7 logMAR letters (p < 0.001) in year 1, and 6.9 (p < 0.001) in year 5. Mean Kmax decreased by 1.2 dioptres (D; p < 0.01) in year 1. During subsequent years the Kmax flattening appeared sustained but this was not statistically significant. K2 flattened significantly from baseline in year 1 and then remained stable. At 1 year, 4.1% patients were poor responders to CXL in terms of VA, losing ≥15 letters. The proportion of the poor responders remained unchanged: 4.9% at 5-years. The proportion of poor responders in terms of Kmax remained similar: 5.9% steepening by ≥2D at 1-year and 7.5% at 5-years. The proportion of K2 poor responders remained stable with 4.7% steepening by ≥2D at 1-year and 5.8% at 5-years. CONCLUSIONS: Cross-linking is effective at stabilising keratoconus up to 5 years in most patients. However, a small proportion of eyes failed to stabilise and had reduced vision.

Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells.

Adipose-derived stem cells are a subtype of mesenchymal stem cell that offers the important advantage of being easily obtained (in an autologous manner) from low invasive procedures, rendering a high number of multipotent stem cells with the potential to differentiate into several cellular lineages, to show immunomodulatory properties, and to promote tissue regeneration by a paracrine action through the secretion of extracellular vesicles containing trophic factors. This secretome is currently being investigated as a potential source for a cell-free based regenerative therapy for human tissues, which would significantly reduce the involved costs, risks and law regulations, allowing for a broader application in real clinical practice. In the current article, we will review the existing preclinical and human clinical evidence regarding the use of such adipose-derived mesenchymal stem cells for the regeneration of the three main layers of the human cornea: the epithelium (derived from the surface ectoderm), the stroma (derived from the neural crest mesenchyme), and the endothelium (derived from the neural crest cells).

Quality of life impact of eye diseases: a Save Sight Registries study.

BACKGROUND: The objectives of this study were to evaluate the quality-of-life (QoL) impact of eye diseases (keratoconus; neovascular age-related macular degeneration, AMD; retinal vein occlusion, RVO; and diabetic macular edema, DME) using the Impact of Vision Impairment (IVI) questionnaire, and to determine the relationship between the IVI scores and visual acuity. METHODS: This cross-sectional, multicentre, real-world study utilised the prospective, web-based Save Sight Registries. The IVI was completed by 1557 patients: 307 with keratoconus, 1049 with AMD, 148 with RVO and 53 with DME. Statistical analysis included Rasch analysis, Welch t-test, one-way ANOVA, Tukey's test, Pearson correlation, and multiple regression. RESULTS: The IVI scales (Overall; Visual Function, VF; Emotional, EM) had robust psychometric properties. The keratoconus patients had the worst Overall (adjusted mean: 48.2 vs. DME 58.8, RVO 64.6, AMD 67.6 units), VF (47.7 vs. DME 59.4, RVO 65.9, AMD 68.9 units) and EM (50.8 vs. DME 63.1, RVO 69.2, AMD 71.8 units) scores (all p < 0.05). The IVI scales scores weakly correlated with better and worse eye visual acuity (Pearson's r 0.24-0.39, all p < 0.05). The correlations were similar in the better eye (Overall 0.35, VF 0.39, EM 0.24) and the worse eye (Overall 0.31, VF 0.33, EM 0.25) visual acuity. Correlations with visual acuity were stronger for VF than for the EM scores. CONCLUSIONS: The IVI was a psychometrically robust QoL questionnaire. Keratoconus patients had worse IVI scores than patients with retinal diseases. The low strength of correlations between visual acuity and QoL scores, although statistically significant, suggested that a complex relationship exists.

Predictors of progression in untreated keratoconus: a Save Sight Keratoconus Registry study.

AIMS: We set out to identify risk factors for progression in untreated keratoconus patients from 34 centres across Australia, New Zealand, Spain and Italy. METHODS: Patients were divided into 'progressors' and 'stable' patients for each clinical parameter: visual acuity (VA), steepest keratometry (maximum keratometry (Max-K)) and thinnest corneal thickness (TCT). Primary outcomes were the proportion of eyes with sustained progression in VA, Max-K or TCT within 3 years. Secondary outcomes included predictors of progression. RESULTS: There were 3994 untreated eyes from 2283 patients. The proportion of eyes with VA, Max-K and TCT progression at 1 year were 3.2%, 6.6% and 3.1% respectively. Factors associated with VA loss were higher baseline VA (HR 1.15 per logMAR line increase in VA; p<0.001) and steeper baseline Max-K (HR 1.07 per 1D increase; p<0.001). Younger baseline age was associated with Max-K steepening (HR 0.96 per year older; p=0.001). Thicker baseline TCT, steeper baseline Max-K and younger baseline age were associated with TCT thinning: (HR 1.08 per 10 µm increase in TCT; p<0.001), (HR 1.03 per 1D increase; p=0.02) and (HR 0.98 per year younger; p=0.01), respectively. CONCLUSIONS: Steeper Max-K and younger age were the most clinically useful baseline predictors of progression as they were associated with worsening of two clinical parameters. Every 1D steeper Max-K was associated with a 7% and 3% greater risk of worsening VA and thinning TCT, respectively. Each 1 year younger was associated with a 4% and 2% greater risk of steepening Max-K and thinning TCT, respectively.

Priming human adipose-derived mesenchymal stem cells for corneal surface regeneration.

Limbal stem cells (LSC) maintain the transparency of the corneal epithelium. Chemical burns lead the loss of LSC inducing an up-regulation of pro-inflammatory and pro-angiogenic factors, triggering corneal neovascularization and blindness. Adipose tissue-derived mesenchymal stem cells (AT-MSC) have shown promise in animal models to treat LSC deficiency (LSCD), but there are not studies showing their efficacy when primed with different media before transplantation. We cultured AT-MSC with standard medium and media used to culture LSC for clinical application. We demonstrated that different media changed the AT-MSC paracrine secretion showing different paracrine effector functions in an in vivo model of chemical burn and in response to a novel in vitro model of corneal inflammation by alkali induction. Treatment of LSCD with AT-MSC changed the angiogenic and inflammatory cytokine profile of mice corneas. AT-MSC cultured with the medium that improved their cytokine secretion, enhanced the anti-angiogenic and anti-inflammatory profile of the treated corneas. Those corneas also presented better outcome in terms of corneal transparency, neovascularization and histologic reconstruction. Priming human AT-MSC with LSC specific medium can potentiate their ability to improve corneal wound healing, decrease neovascularization and inflammation modulating paracrine effector functions in an in vivo optimized rat model of LSCD.

A Risk Prediction Model for Endothelial Keratoplasty After Uncomplicated Cataract Surgery in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To develop a risk prediction model for endothelial keratoplasty (EK) after uncomplicated cataract surgery in Fuchs endothelial corneal dystrophy (FECD) using Scheimpflug imaging. DESIGN: Prospective, observational cohort study. METHODS: The study was conducted at the Ramón y Cajal University Hospital (Madrid, Spain) on 127 eyes from 93 consecutive patients with vision loss, FECD, and cataracts. OBSERVATION: We assessed the corneas using Scheimpflug imaging pachymetry and elevation maps for loss of regular isopachs, displacement of the thinnest point, and posterior surface depression according to the Mayo Clinic subclinical corneal edema classification. We also recorded other preoperative data. Primary Endpoints: The primary endpoint was the need for EK after uncomplicated phacoemulsification within 2 years (median duration, 18 months). We calculated the risk using hazard ratios and the Kaplan-Meier cumulative incidence risk. RESULTS: Forty-four participants required EK, and those eyes with 1, 2, or all 3 tomographic features had a hazard risk of 21.8, 57.2, and 76.5, respectively (P < .005), compared with those eyes with normal tomographic patterns. The best predictive model was based on the number of tomographic features simultaneously present in an eye and the central corneal thickness (CCT) at the pupillary center. We aimed to develop a risk score from 0 to 8. The cumulative risk for EK ranged from virtually 0 for risk scores <4 to almost 100% for those with a score of 8. CONCLUSIONS: The combination of CCT values and tomographic features can be employed to make valid predictions of the risk of requiring EK after phacoemulsification.

Epidemiology of pseudomembranous conjunctivitis in a tertiary hospital: A 2-year retrospective study.

PURPOSE: To describe the incidence, duration, and complication rate of patients with a clinical diagnosis of pseudomembranous viral conjunctivitis. METHODS: A retrospective observational study is performed compiling the data of patients diagnosed as pseudomembranous conjunctivitis at the hospital's emergency department from June 2016 to May 2018. Demographic variables, duration of symptoms, and follow-up until resolution of the pseudomembranes and associated complications are collected. RESULTS: The incidence rate of pseudomembranous conjunctivitis is 3.47/10,000 people-year and 0.123% of emergency department consultations. The incidence of pseudomembranous conjunctivitis is approximately 20% of the total adenoviral conjunctivitis, with similar peak incidence rates and annual distribution. The presence of pseudomembranes shows a mean duration of 7.86 days. In this series of pseudomembranous patients, 38.4% had at least one of the following complications: 16.7% subepithelial infiltrates (IC 13.0%-21.1%), 20.81% corneal erosions (SE 0.0218, IC 16.7%-25.5%), 3.5% filamentary keratitis (SE 0.010, IC 1.8%-6.0%), and 6.1% subtarsal fibrosis (SE 0.128, IC 3.8%-9.1%). CONCLUSION: To the best of our knowledge, this is the first study to investigate the incidence and rate of complications of pseudomembranous conjunctivitis. Complications occurred in almost 4 out of 10 patients. The mean duration of the follow-up in the ED was higher in patients with any complication compared with non-complicated patients. The high complication rate makes a closely follow-up advisable, until pseudomembrane resolution, to assess possible complications and symptomatic treatment.

Corneal graft failure: an update.

Corneal graft surgery is one of the most successful forms of human solid-tissue transplantation, and nowadays, there is a worldwide expansion of the surgical volume of corneal grafts. This surgery is continuously evolving, with new surgical techniques and postoperative treatments that have considerably increased the chance of survival for the grafts. Despite the high rate of success, corneal transplantation is still complicated by a relevant risk of graft failure. This study investigates the causes that lead to the failure of the different corneal graft surgical techniques and provides an updated synthesis on this topic. A comprehensive review of the main pathological pathways that determine the failure of corneal grafts is provided, analysing the main risk factors and disclosing the survival rates of the principal form of corneal grafts. Our results revealed that penetrating keratoplasty has higher failure rates than lamellar keratoplasty, with immunological rejection being the leading cause of graft failure, followed by late endothelial failure (LEF) and ocular surface disorders. Postoperative glaucoma and dehiscence of the surgical wound represent other important causes of failure. Endothelial keratoplasty showed the lowest rates of failure in the mid-term, with LEF, detachment of the graft and primary graft failure representing the most common pathological reasons for failure.

Corneal stroma regeneration: Preclinical studies.

Corneal grafting is one of the most common and successful forms of human tissue transplantation in the world, but the need for corneal grafting is growing and availability of human corneal donor tissue to fulfill this increasing demand is not assured worldwide. The stroma is responsible for many features of the cornea, including its strength, refractive power and transparency, so enormous efforts have been put into replicating the corneal stroma in the laboratory to find an alternative to classical corneal transplantation. Unfortunately this has not been yet accomplished due to the extreme difficulty in mimicking the highly complex ultrastructure of the corneal stroma, and none of the obtained substitutes that have been assayed has been able to replicate this complexity yet. In general, they can neither match the mechanical properties nor recreate the local nanoscale organization and thus the transparency and optical properties of a normal cornea. In this context, there is an increasing interest in cellular therapy of the corneal stroma using Induced Pluripotent Stem Cells (iPSCs) or mesenchymal stem cells (MSCs) from either ocular or extraocular sources, as they have proven to be capable of producing new collagen within the host stroma, modulate preexisting scars and enhance transparency by corneal stroma remodeling. Despite some early clinical data is already available, in the current article we will summary the available preclinical evidence about the topic corneal stroma regeneration. Both, in vitro and in vivo experiments in the animal model will be shown.

Corneal Stroma Regeneration: New Approach for the Treatment of Cornea Disease.

Corneal grafting is one of the most common forms of human tissue transplantation. The corneal stroma is responsible for many characteristics of the cornea. For these reasons, an important volume of research has been made to replicate the corneal stroma in the laboratory to find an alternative to classical corneal transplantation techniques.There is an increasing interest today in cell therapy of the corneal stroma using induced pluripotent stem cells or mesenchymal stem cells since these cells have shown to be capable of producing new collagen within the host stroma and even to improve its transparency.The first clinical experiment on corneal stroma regeneration in advanced keratoconus cases has been reported and included. Fourteen patients were randomized and enrolled into 3 experimental groups: (1) patients underwent implantation of autologous adipose-derived adult stem cells alone, (2) patients received decellularized donor corneal stroma laminas, and (3) patients received implantation of recellularized donor laminas with adipose-derived adult stem cells. Clinical improvement was detected with all cases in their visual, pachymetric, and topographic parameters of the operated corneas.Other recent studies have used allogenic SMILE implantation lenticule corneal inlays, showing also an improvement in different visual, topographic, and keratometric parameters.In the present report, we try to summarize the available preclinical and clinical evidence about the emerging topic of corneal stroma regeneration.

Characteristics, Behaviors, and Awareness of Contact Lens Wearers Purchasing Lenses Over the Internet.

OBJECTIVES: To describe the characteristics and hygiene habits of contact lens (CL) wearers who acquire CLs over the Internet, as well as their awareness of modifiable risk factors (RFs). METHODS: A web-based survey was conducted among clients of an online CL sales platform during 6 months. Demographic data, CL hygiene-related awareness, and compliance were collected and analyzed. RESULTS: The questionnaire was completed by 1,264 CL wearers: the average age was 40.8 years; most were women (71.1%), had myopia (76.4%), and wore monthly disposable CLs (63.6%). The frequency of eye examination was significantly lower among those buying the CL exclusively online (15.8% vs. 6.6%, P<0.001) and those who had begun CL use on their own (17.5% vs. 8.8%, P<0.001). Initiation to CL wear without the intervention of an eye care practitioner was more frequent in wearers with less experience. Common risk behaviors included water exposure (68.1% in swimming and 64.9% in the shower), use of the case (61.9%) and CL (65.1%) beyond the recommended replacement time, and reuse of the maintenance solution (31.9%). Ignorance of recommended hygiene increased the probability of risky behavior. CONCLUSION: There were no differences in compliance or awareness of risks between those purchasing exclusively online and other CL wearers. However, the growing frequency of self-taught initiation in CL wear among less-experienced online customers and online exclusive purchase was associated with a decrease in eye examination frequency and therefore worse compliance and increased risks. This finding underlines the importance of publicizing correct hygiene habits by all possible means so as to increase compliance.

Artificial neural network to guide intracorneal ring segments implantation for keratoconus treatment: a pilot study.

BACKGROUND: To analyze the clinical results of an artificial neural network (ANN) that has been processed in order to improve the predictability of intracorneal ring segments (ICRS) implantation in keratoconus. METHODS: This retrospective, comparative, nonrandomized, pilot, clinical study included a cohort of 20 keratoconic eyes implanted with intracorneal ring segments KeraRing (Mediphacos, Belo Horizonte, Brazil) using the ANN (ANN group) and 20 keratoconic eyes implanted with KeraRing using the manufacturer's nomograms (nomogram group). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA) (visual acuity is expressed in decimal value and in LogMAR value in brackets), manifest refraction, corneal topography, tomography, aberrometry, pachymetry and volume analysis (Sirius System. CSO, Firenze, Italy) were performed during the preoperative visit; and the two groups, ANN group and nomogram group, did not differ significantly preoperatively in all of the parameters evaluated. These preoperative values were compared with the results obtained at the third-month visit. Mann-Whitney test and Wilcoxon test were used for the statistical analyses. RESULTS: The spherical equivalent and the keratometric values decreased significantly in both groups. The CDVA improved from 0.60 ± 0.23 (0.22 LogMAR) pre-operatively to 0.73 ± 0.21 (0.14 LogMAR) post-operatively in the ANN group (p < 0.005), and from 0.54 ± 0.19 (0.27 LogMAR) pre-operatively to 0.62 ± 0.19 (0.21 LogMAR) post-operatively in the nomogram group (p < 0.01), with statistically significant difference between the two groups (p < 0.05), being better in the ANN group. Coma-like aberrations decreased significantly in the ANN group, while in the nomogram group they did not change significantly, but no statistically significant difference was found between the two groups. CONCLUSIONS: ANN to guide ICRS provides an increase in the visual acuity, reduction in the spherical equivalent and improvement in the optical quality of keratoconus patients. ANN gives better results when compared with the manufacturer's nomograms in terms of better corrected vision and reduction of the coma-like aberrations. The constant inclusion of new cases will make the predictability of ANN increasingly better as the software finetunes its learning.

Treatment of corneal endothelial damage in a rabbit model with a bioengineered graft using human decellularized corneal lamina and cultured human corneal endothelium.

OBJECTIVE: We aimed to investigate the functionality of human decellularized stromal laminas seeded with cultured human corneal endothelial cells as a tissue engineered endothelial graft (TEEK) construct to perform endothelial keratoplasty in an animal model of corneal endothelial damage. METHODS: Engineered corneal endothelial grafts were constructed by seeding cultured human corneal endothelial cell (hCEC) suspensions onto decellularized human corneal stromal laminas with various coatings. The functionality and survival of these grafts with cultured hCECs was examined in a rabbit model of corneal endothelial damage after central descemetorhexis. Rabbits received laminas with and without hCECs (TEEK and control group, respectively). RESULTS: hCEC seeding over fibronectin-coated laminas provided an optimal and consistent endothelial cell count density and polygonal shape on the decellularized laminas, showing active pump fuction. Surgery was performed uneventfully as standard Descemet stripping automated endothelial keratoplasty (DSAEK). Corneal transparency gradually recovered in the TEEK group, whereas haze and edema persisted for up to 4 weeks in the controls. Histologic examination showed endothelial cells of human origin covering the posterior surface of the graft in the TEEK group. CONCLUSIONS: Grafting of decellularized stroma carriers re-surfaced with human corneal endothelial cells ex vivo can be a readily translatable method to improve visual quality in corneal endothelial diseases.

Preoperative Risk Assessment for Progression to Descemet Membrane Endothelial Keratoplasty Following Cataract Surgery in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To identify preoperative corneal tomographic features that predict progression to endothelial keratoplasty (EK) following cataract surgery in Fuchs endothelial corneal dystrophy (FECD) and establish a regression model to identify high-risk patients. DESIGN: Prospective, observational cohort study. METHODS: Setting: Hospital Universitario Ramón y Cajal, Madrid, Spain. STUDY POPULATION: Sixty-eight patients (84 eyes) with FECD who underwent phacoemulsification. INTERVENTION: We assessed preoperative best-corrected visual acuity; ultrasound central corneal thickness; pachymetric, anterior chamber depth, and corneal backscatter variables using Scheimpflug imaging; and endothelial cell density. MAIN OUTCOME MEASURES: Progression to EK. RESULTS: A total of 33 eyes (39.3%) needed EK after phacoemulsification to rehabilitate vision. On multivariate analysis, anterior layer (AL) corneal backscatter between 0 and 2 mm from the apex and relative increase in central corneal thickness from the "relative pachymetry display" by the Pentacam were significant predictors of the risk of progression to EK. Using these 2 variables, a risk score (RISC score) was derived from the regression model (area under the curve = 0.973; best cutoff point with a specificity of 95% representing a sensitivity of 96%). Excluding corneal backscatter data from the multivariate regression model, corneal thickness at the pupil center by the Pentacam and relative increase in central corneal thickness were significant predictors and provided a modified risk score (RIPT score) with similar performance. CONCLUSION: Both scores demonstrated accuracy in predicting progression to EK using easily accessible preoperative data. This approach, which can be readily implemented by surgeons, allows for individualized risk assessment.