Purpose To evaluate vision-related quality of life (VR-QoL) in keratoconus using the Portuguese-validated Keratoconus Outcomes Research Questionnaire (KORQ), explore its association with clinical and tomographic parameters, and assess short-term changes following corneal collagen cross-linking (CXL). Design Single-center observational study comprising a cross-sectional analysis and a prospective cohort. Subjects 153 keratoconus patients were enrolled in the cross-sectional analysis, including 25 compared with 25 age-matched healthy controls. The prospective cohort included 32 patients (17 undergoing CXL, 15 untreated). Methods KORQ subscale scores were examined for associations with visual acuity, keratometric parameters, and tomographic staging. Prospective participants completed the KORQ at baseline and 6 months, with longitudinal changes analyzed using a two-way mixed analysis of variance. Results Keratoconus patients reported significantly worse VR-QoL than controls on both subscales (Activity Limitation: p = 0.046, r = 0.33; Symptoms: p = 0.013, r = 0.41). Activity Limitation scores showed modest but significant associations with keratometric severity, most notably with Kmax (ρ=−0.278, p = 0.001), while Symptoms were independent of clinical parameters. CXL was associated with short-term clinical improvement and keratometric stabilization. A significant Time×Treatment interaction was observed for the Symptoms subscale in unadjusted (p = 0.004) and adjusted analyses (p = 0.022), indicating a differential evolution of symptoms between groups. Conclusions Keratoconus is associated with a substantial reduction in VR-QoL that only partly correlates with standard clinical and tomographic measures. A differential evolution of symptom perception was observed between treated and untreated patients, persisting after adjustment for key baseline covariates. These results support the use of the KORQ as a complementary outcome measure in keratoconus research and clinical practice.

Purpose: To evaluate the intrasession repeatability and agreement in keratometric and wavefront measurements among three different instruments (Pentacam HR, Nidek OPD-Scan III [OPD], and Zeiss i-Profiler Plus [IPROF]) in a pediatric population with various clinical features. Methods: This cross-sectional study included 217 eyes from 114 patients aged 6 to 17 years with different clinical features. The patients were divided into five groups: one control group (C) and four other groups, each presenting with keratoconus (KC), ocular allergy (OA), high astigmatism, or Down syndrome (DS). Statistical analyses included the intraclass correlation coefficient (ICC) for repeatability and Bland-Altman plots for agreement. Results: The findings demonstrated excellent repeatability of keratometric parameters across all devices (e.g., K1 ICC: 99.53% for Pentacam, 98.10% for OPD, and 98.31% for IPROF). The Pentacam showed superior repeatability for aberrometry indices in the KC group, with ICC values exceeding 98% for high-order aberration root mean square (HOA RMS) and Zernike polynomials. However, in the DS group, repeatability was significantly reduced for certain parameters, such as the index of surface variance (ICC: 40.13%) and HOA RMS (ICC: 42.86%). Bland-Altman plots revealed variations among devices in asphericity, vertical coma, and HOA RMS, with the KC group exhibiting broader limits of agreement compared to the control group. Conclusion: All three instruments showed good repeatability, with the Pentacam demonstrating superior reliability across all parameters, including aberrometry. However, agreement between devices was poor for key indices in patients with KC and DS.

Purpose: To assess the accuracy of various Pentacam indices in distinguishing keratoconus (KC) in pediatric patients with high astigmatism and to establish appropriate cutoff values. Methods: This prospective multicenter cross-sectional study included 312 eyes from 167 patients aged 6 to 18 years (mean age, 13.1 ± 3.2 years) evaluated with Oculus Pentacam HR. Patients were categorized into 4 groups: KC, forme fruste keratoconus, astigmatism greater than 2 diopters (Cyl2D), and control. A subgroup of Cyl2D comprised patients with astigmatism greater than 4 diopters (Cyl4D). Twenty-three Pentacam indices were analyzed, and receiver operating characteristic curves determined optimal cutoff points, sensitivity, and specificity. Results: The best indices for distinguishing KC from Cyl2D were high-order aberration root mean square of the anterior corneal surface (area under the receiver operating characteristic curve 0.987), Belin/Ambrosio enhanced ectasia total derivation (0.971), index of vertical asymmetry (0.971), average pachymetric progression index (0.962), maximum Ambrosio relational thickness (0.960), posterior elevation (0.952), and anterior elevation (0.948). The accuracy of these indices was highest in the control group and lowest in the Cyl4D group. Area under the receiver operating characteristic curve was significantly lower for fruste keratoconus than KC. Optimal cutoff values were higher for astigmatic patients than for those with no refractive error. Conclusions: Most indices effectively distinguished between KC and normal pediatric patients. For individuals with high astigmatism, we suggest focusing on specific indices such as high-order aberration root mean square, Belin/Ambrosio enhanced ectasia total derivation value, maximum Ambrosio relational thickness, average pachymetric progression index, and index of vertical asymmetry. Optimal cutoff points for these patients were higher than those for nonastigmatic children and differed from adult populations.

Introduction Keratoconus patients turn to the internet for answers to their disease expectations. Webpages are not filtered or submitted to evaluation before getting published. We aim to evaluate the quality and readability of the online information regarding keratoconus in Portugal and Brazil.Methods Two independent ophthalmologists and one ophthalmologist supervisor evaluated 30 Portuguese and 30 Brazilian websites by order of appearance in Google with the word "Queratocone" and "Ceratocone", respectively. Two quality scores were used: a quality index of consumer health information (DISCERN) and the Journal of the American Medical Association (JAMA) benchmark. Readability was evaluated with 3 scores: FleschKincaid Reading Ease (FRE), FleschKincaid Grade (FKG) and Automated Readability Index (ARI).Results Sites from private hospitals or clinics were the most prevalent in both countries, followed by health platform sites. Final JAMA benchmark was 1.13 +/- 1.18 in Portugal and 1.07 +/- 1.00 in Brazil. Final DISCERN was 34.07 +/- 11.71 in Portugal and 38.17 +/- 10.51 in Brazil. FRE and FKG scores denoted "difficult to read" and "college school level" in both countries; ARI denoted "professor" level in Portugal and "college student" level in Brazil needed to understand the text, a statistically significant difference. There was no correlation between Google ranking and quality and readability scores.Discussion and Conclusions The information on keratoconus available online to Portuguese-speaking patients is of poor quality and difficult to interpret. Ophthalmologists have a shared responsibility to tackle this challenge through multifold efforts. Educating our patients on how to find reputable websites can help them navigate their life with keratoconus.

The study aimed to evaluate the precision of different Pentacam indices in diagnosing keratoconus (KC) in pediatric patients with and without Down Syndrome (DS) and determine suitable cutoff values. This prospective multicenter cross-sectional study evaluated 216 eyes of 131 patients aged 6–18 years (mean age 12.5 ± 3.2 years) using Pentacam. Patients were categorized into four groups: KC, forme fruste keratoconus (FK), DS, and control, excluding DS patients with topographic KC. Receiver operating characteristic curves were generated to determine the optimal cutoff points and compare the accuracy in identifying KC and FK in patients with and without DS. In DS patients, corneal morphology resembled KC features. The most effective indices for distinguishing KC in DS patients were the average pachymetric progression index (AUC = 0.961), higher-order aberration of the anterior cornea (AUC = 0.953), anterior elevation (AUC = 0.946), posterior elevation (AUC = 0.947), index of vertical asymmetry (AUC = 0.943), and Belin/Ambrosio enhanced ectasia total derivation value (AUC = 0.941). None of the indices showed good accuracy for distinguishing FK in DS patients. The thresholds of these indices differed significantly from non-DS patients. The results highlighted the need for DS-specific cutoff values to avoid false-positive or false-negative diagnoses in this population.

Purpose The purpose of this study was to assess the use of topical tacrolimus ointment in preventing rejection in high-risk corneal grafts, when added to the standard immunosuppressive regimen. Methods We conducted an observational, retrospective study using clinical data of high-risk patients subjected to penetrating keratoplasty, who were treated with topical tacrolimus ointment 0.2 mg/g twice a day plus topical dexamethasone 0.1 mg/ml 6 id and compared it with a similar control group treated with topical dexamethasone 0.1 mg/ml 6 id alone. High-risk status was attributed to patients with previous ipsilateral corneal graft failure, two or more quadrants with corneal neovascularization or an infectious or inflammatory corneal disease. Results We analysed 53 patients in the trial group versus 53 patients in the control group, with similar age, baseline diagnosis and risk factors, and median follow-up times of 30 and and 24 months, respectively. Survival analysis showed a higher graft survival rate at all follow-up periods for patients treated with topical tacrolimus (p < 0.01). No adverse reactions were reported. Discussion This study shows that topical tacrolimus ointment increases the survival rate of the graft if added to the previous topical steroid regimen in high-risk patients. Conclusion Topical tacrolimus is safe and effective in prolonging graft survival in high-risk patients.

Keratoconus (KC) is a bilateral progressive corneal ectasia resulting in irregular astigmatism and loss of visual function, in youth and children. Corneal cross‐linking (CXL) is the standard treatment to halt the progression of KC. The conventional protocol consists of removal of the corneal epithelium (epi‐off), followed by soaking of riboflavin and then irradiation with UVA light, leading to stiffening of the cornea. However, postoperative ocular adverse events related to epithelial removal, such as infectious keratitis and delayed visual recovery, have been described. Some alternative methodologies have been tested but pain, no control on corneal permeability, and high investment for set‐up acquisition are drawbacks. Accordingly, the treatment of KC is at an extremely exciting stage, and research on delivering riboflavin into the cornea without removing the epithelium is underway. To address this clinical unmet need, we developed an advanced solution consisting of nanoparticle‐modified commercial soft contact lenses. Safety conditions were determined using ex vivo porcine eyes. The efficacy of our solution on corneal epithelial permeability to riboflavin was tested using in vivo rat eyes. Our nanotechnology‐based solution allows high spatial and temporal precision control of epithelial permeability to riboflavin. We aim to validate this innovative strategy as an epithelium‐on (epi‐on) protocol for the effective treatment of KC, with obvious advantages in terms of safety, patient comfort, and recovery time. Furthermore, our strategy is compatible with current equipment and riboflavin solutions, allowing to capitalize clinicians' expertise and the resources already existing in private clinics and public health services. This project was financially supported by Foundation for Science and Technology (FCT, Portugal): Exploratory Research Project EXPL/BIA‐BQM/0042/2021, Strategic Projects UIDB/04539/2020, UIDP/04539/2020, and UID/NEU/04539/2019; and by COMPETE‐FEDER (POCI‐01‐0145‐FEDER‐007440).

OBJECTIVE:To compare cross-linking (CXL) plus topography-guided photorefractive keratectomy (t-PRK) and intrastromal corneal ring segments (ICRS) in keratoconus patients, at 12 months of follow-up. METHODS:This was a longitudinal, retrospective multi-center study. We included a referred sample of 154 eyes from 149 patients with grade I-III Amsler-Krümeich keratoconus with insufficient corrected-distance visual acuity (CDVA). In group 1 (CXL plus t-PRK, 87 eyes), another possible indication for surgery was evidence of progression. Group 2 (ICRS, 67 eyes) included only eyes with paracentral keratoconus (thinnest point at the inferotemporal quadrant) with coincident axes, and evidence of stabilization was required. A subgroup analysis was performed regarding the disease topographic phenotype. At 12 months postoperatively, visual, refractive, and topographic outcomes were evaluated. RESULTS:Comparison of the outcomes between CXL plus t-PRK (group 1) and ICRS (group 2) showed similar improvements in CDVA (in group 1, CDVA improved 0.18 logMAR, and in group 2 0.12 logMAR, P = .18) and K2 (-2,45 [6.46] D in group 1 and -2.13 [1.67] D in group 2, P = .34) The improvement in cylinder power was greater in group 2 (-2.37 [2.07] D in group 2 versus -1.18 [2.63] D in group 1, P = .003); group 1 had a higher decrease in Kmax (- 3.26 [3.64] versus-1.74 [2.67], P = .001). CONCLUSIONS:Both CXL plus t-PRK and ICRS were equally effective in improving CDVA and topographic parameters in a similar group of keratoconus patients at 12 months.

At the age of 43 years-old, a man was left with bilateral limbal stem cell deficiency after an ocular alkaline burn with lime, which resulted in corneal opacification. After multiple unsuccessful surgical attempts to restore vision, including penetrating keratoplasties and Boston keratoprosthesis, visual acuity was counting fingers in the left eye. At 73 years of age, the patient underwent another surgery in his left eye. Cauterization of neovessels and removal of the vascular pannus were followed by partial excision of Tenon's capsule. Penetrating keratoplasty was followed by an intrastromal injection of anti-VEGF (vascular endothelial growth factor), and the ocular surface was covered with amniotic membrane. Postoperatively, the graft was clear with no signs of inflammation; vision improved to 20/50 and remained stable throughout the following two years. Herein we describe some adjunctive procedures that might have delayed failure and rejection of the corneal graft. This case demonstrates the difficulties in treating bilateral limbal stem cell deficiency in a tertiary eye care center with no capacity to perform stem cell therapy.

OBJECTIVE:To assess the possible correlation between patients' personality traits and subjective perception of quality of vision (QoV), after multifocal intraocular lens (mIOL) implantation. METHODS:patients who had bilateral implantation of a non-diffractive X-WAVE or a trifocal lens were assessed 6 months postoperatively. Patients answered the NEO-Five Factor Inventory (NEO-FFI-20) questionnaire ("Big Five five-factor personality model") to examine their personality. Six months following surgery, patients were asked to fill a QoV questionnaire where they graded the frequency of 10 common visual symptoms. Primary outcomes were to evaluate the correlation between personality scores and the reported frequency of visual disturbances. RESULTS:The study comprised 20 patients submitted to bilateral cataract surgery, 10 with a non-diffractive X-WAVE lens (AcrySof® IQ Vivity) and 10 with a trifocal lens (AcrySof® IQ PanOptix). Mean age was 60.23 (7.06) years. Six months following surgery, patients with lower scores of conscientiousness and extroversion reported a higher frequency of visual disturbances (blurred vision, P  =  .015 and P  =  .009, seeing double images P  =  .018 and P  =  .006, and having difficulties focusing, P  =  .027 and P  =  .022, respectively). In addition, patients with high neuroticism scores had more difficulty focusing (P  =  .033). CONCLUSIONS:In this study, personality traits such as low conscientiousness and extroversion and high neuroticism significantly influenced QoV perception 6 months after bilateral multifocal lens implantation. Patients' personality questionnaires could be a useful preoperative assessment test to a mIOL.

Objective Dry eye disease (DED) is a multifactorial disease involving the tears and ocular surface. It impacts a patient’s quality of life (QoL) and ability to perform daily activities. This study assessed the burden of self-reported DED among adults in eight European countries. Design Online cross-sectional survey. Setting General population in France, Italy, Germany, Greece, the Netherlands, Portugal, Spain and Sweden. Participants Adults aged ≥18 years with (n=6084) and without (n=6161) self-reported DED were recruited via emails and screened. Main outcome measures All participants completed National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) and EuroQol-5 Dimension-5 Level Questionnaire (EQ-5D-5L). All DED participants completed the Eye Dryness Score (EDS) Visual Analogue Scale, and Ocular Comfort Index and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem questionnaires. In addition, half of the respondents with DED completed Survey A (Impact of Dry Eye on Everyday Life) and the other half completed Survey B (Standard Patient Evaluation of Eye Dryness Questionnaire) and Dry Eye Questionnaire-5. Results Participants with self-reported DED had lower functional vision and lower overall health status than participants without self-reported DED as measured by the NEI-VFQ and EQ-5D-5L, respectively. Increasing self-reported DED severity as measured by the EDS was shown to correspond with worse symptom severity/frequency, lower functional vision, higher impact on work productivity, daily activities and QoL. Conclusion This study showed that patients’ reported burden of self-reported DED was similar across the eight European countries. Those with self-reported DED reported lower health status and functional vision compared to those without self-reported DED and these parameters worsen with increasing disease severity.

Two-photon imaging (TPI) microscopy, namely, two-photon excited fluorescence (TPEF), fluorescence lifetime imaging (FLIM), and second-harmonic generation (SHG) modalities, has emerged in the past years as a powerful tool for the examination of biological tissues. These modalities rely on different contrast mechanisms and are often used simultaneously to provide complementary information on morphology, metabolism, and structural properties of the imaged tissue. The cornea, being a transparent tissue, rich in collagen and with several cellular layers, is well-suited to be imaged by TPI microscopy. In this review, we discuss the physical principles behind TPI as well as its instrumentation. We also provide an overview of the current advances in TPI instrumentation and image analysis. We describe how TPI can be leveraged to retrieve unique information on the cornea and to complement the information provided by current clinical devices. The present state of corneal TPI is outlined. Finally, we discuss the obstacles that must be overcome and offer perspectives and outlooks to make clinical TPI of the human cornea a reality.

Introduction: The purpose of this study is to evaluate the stability of crosslinking (CXL) treatment associated with photorefractive keratectomy (PRK) with excimer laser in patients with keratoconus, through comparison of keratometric and topographic parameters and functional results at 6 months postoperatively and at the last evaluation. Methods: Seventy-four eyes of 71 patients with established kerotoconus who had contact lens intolerance and/or disease progression were included. The eyes were submitted to CXL plus partial PRK and a residual stromal thickness of 325 μm in the end of the laser procedure was required. We compared uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), refractive sphere and cylinder, keratometric parameters (K1, K2, Kmax, average K) and minimum pachymetry at 6 months and at last evaluation. Results: The mean age was 32.12±9.73 years. We report the results at 6 months and last evaluation (occurred between 12 and 37 months postoperatively), mean 17.09±6.39 months. All parameters (K1, K2, average K, maximum K, K1 axis, spherical equivalent and minimum pachymetry) remained stable, except for BCVA which improved 0.05 logMAR (p<0.05). No patient lost more than two lines of Snellen chart and the greatest improvement was five lines. Conclusion: Our results suggest that accelerated CXL with topography-guided PRK in keratoconic eyes resulted in progressive BCVA improvement between 6 months and 12 to 37 months postoperatively. Keratometric and topographic values remained stable postoperatively, confirming the efficacy of the procedure in arresting progression of keratoconus.

Purpose:To compare the results between photorefractive keratectomy (PRK) with Custom-Q or with Wavefront-optimized (WFO) profiles in terms of asphericity and spherical aberrations, 6 months post-operative. Setting:Tertiary referral center (Centro Hospitalar e Universitario da Universidade de Coimbra, Coimbra, Portugal). Patients and Methods: Fifty-nine eyes (43 patients) were enrolled on this retrospective case series, including patients with myopia and/or astigmatism, submitted to refractive surgery with PRK (Allegretto WAVE Eye-Q Excimer Laser System, Alcon), in a Custom-Q ablation (38 eyes) or Wavefront-optimized procedure (21 eyes). We included patients with a minimum follow-up of 6 months; age over 21 years; stable refractive error for 2 years; spherical equivalent (SE) inferior to 5.50 diopters (D); percentage of altered tissue under 40% and expected final corneal curvature above 35 D. Eyes with other ophthalmological pathologies were excluded. Baseline and post-operative asphericity and optical aberrations were evaluated with Pentacam (Oculus Optikgerate, Wetzlar, Germany). Results: The demographic and preoperative refractive data was similar between groups (all p≥0.05). Post-operative spherical equivalent in the Custom-Q and Wavefront-optimized groups was within 0.50D in 100% and 78.90% of eyes, respectively and within 0.25D in 97.06% and 73.70% of eyes, respectively. Variation of Q-value was 0.62±0.34. (range -0.07-1.24) for Custom Q group, and 0.65±0.39 (range -0.05-1.40) in the Wavefront-optimized group (p=0.82). In a multivariate linear regression model, variation of Q-value was not influenced by the ablation profile (B=0.04, p=0.49, 95%CI [-0.08,0.17]). SE was a strong predictor (B=-0.30, p<0.01, 95%CI[-0.39,-0.21]). There was a significant increase in RMS higher-order aberrations (p<0.01for both groups) and no difference between groups (p=0.53). Discussion and Conclusion: In our sample,Custom-Q ablation was not significantly different from Wavefront optimized ablation regarding post-operative asphericity. Although the increase in higher-order aberrations, both techniques were effective and safe for myopic and/or astigmatic correction up to -5.50D SE.

Introduction: Infectious keratitis is an important cause of visual loss. The purpose of this study was to investigate anterior segment optical coherence tomography patterns in infectious keratitis and evaluate the role of this tool in the early management of this disorder. Material and Methods: In this cross-sectional study, we included patients with proven infectious keratitis, either by culture or therapeutic trial. Subjects underwent baseline anterior segment optical coherence tomography (Spectralis® anterior segment module, Heidelberg Engineering, Germany) performed by the same operator. We used anterior segment optical coherence tomography vertical and horizontal raster default scans with 6.0 mm scan lines. Results: Twenty-five patients (14 men and 11 women) were included. The most common risk factors identified were ocular trauma (11 cases) and contact lens wear (7 cases). Fifteen patients presented bacterial infection; three, fungal infection; two parasitic infection; and five cases presented a negative microbiological culture. Anterior segment optical coherence tomography depicted nine distinct morphological patterns. Discussion: Anterior segment optical coherence tomography allows the depth of corneal involvement to be assessed. When the only patterns identified were hyperreflective stromal lesion and stromal edema, the visual outcome was better. Cystic spaces were present in severe bacterial keratitis. Conclusion: Anterior segment optical coherence tomography can complement biomicroscopy, allowing for a better characterization of corneal involvement at presentation that can help in staging and providing useful prognostic information.

Introduction: Infectious keratitis is an important cause of visual loss. The purpose of this study was to investigate anterior segment optical coherence tomography patterns in infectious keratitis and evaluate the role of this tool in the early management of this disorder. Material and Methods: In this cross-sectional study, we included patients with proven infectious keratitis, either by culture or therapeutic trial. Subjects underwent baseline anterior segment optical coherence tomography (Spectralis® anterior segment module, Heidelberg Engineering, Germany) performed by the same operator. We used anterior segment optical coherence tomography vertical and horizontal raster default scans with 6.0 mm scan lines. Results: Twenty-five patients (14 men and 11 women) were included. The most common risk factors identified were ocular trauma (11 cases) and contact lens wear (7 cases). Fifteen patients presented bacterial infection; three, fungal infection; two parasitic infection; and five cases presented a negative microbiological culture. Anterior segment optical coherence tomography depicted nine distinct morphological patterns. Discussion: Anterior segment optical coherence tomography allows the depth of corneal involvement to be assessed. When the only patterns identified were hyperreflective stromal lesion and stromal edema, the visual outcome was better. Cystic spaces were present in severe bacterial keratitis. Conclusion: Anterior segment optical coherence tomography can complement biomicroscopy, allowing for a better characterization of corneal involvement at presentation that can help in staging and providing useful prognostic information.

Objective: the aim of this study is to determine the recent trends in corneal transplant indications and corneal tissue use in Coimbra. Methods: data concerning all corneal transplantation procedures performed at Centro Hospitalar e Universitario de Coimbra (CHUC) between 2011 and 2016 were collected and stored at the CHUC Eye Bank. We retrospectively analysed recipient age, gender, primary diagnosis and transplantation technique. Results: 710 corneal transplants were reviewed for analysis. Regraft accounted for 207 (29.2%) of all procedures, followed by bullous keratopathy, with 125 cases (17.6%) and keratoconus, with 118 cases (16.6%). No statistically significant shift in indications for grafting was identified over the 6-year period (p = 0.70). Penetrating keratoplasty (PK) accounted for 506 procedures (71.3%), Descemet’s stripping automated endothelial keratoplasty (DSAEK) for 129 (18.2%), and deep anterior lamellar keratoplasty (DALK) for 64 (9.0%). Over the 6 years, we observed a statistically significant decline in the numbers of PK, accompanied by an increase in DSAEK and DALK. Conclusions: Eye bank registries provide an effective means to evaluate corneal transplantation evolution. Transplant indications have remained stable across the time frame considered. Compared with other series, we report more repeat grafts, less keratoconus and similar percentages of bullous keratopathy and corneal dystrophies. In terms of surgical technique, this study provides further evidence of the increasing popularity of lamellar keratoplasties, in opposition to PK. In conclusion, the indications and techniques for corneal transplantation continue to evolve rapidly, and merit continued investigation to optimize the activities of eye banks and transplant centres.

RESUMO Os AA fazem considerações sobre clínica, diagnóstico e tratamento do Glaucoma Facomórfico, e ilustram com a apresentação e discussão em quatro pacientes.

PURPOSE To evaluate the efficacy and tolerance of a new matrix-regenerating agent (RGTA), Cacicol®, a polymer that mimics heparan sulfates bound to extracellular matrix proteins, avoiding its proteolysis, to treat neurotrophic keratopathy (NK). METHODS Uncontrolled prospective clinical study performed between January 2014 and May 2016. Twenty-five patients (25 eyes) with corneal neurotrophic ulcers, nonresponsive to at least 2 weeks of conservative therapy, were treated with Cacicol, instilled once/twice a week. During follow-up, slit-lamp examination, anterior segment photography, fluorescein-dye testing, and best-corrected visual acuity were analyzed. Ulcer evolution was evaluated using image analysis software (ImageJ®) and healing defined as decrease of the corneal ulcer area. An independent observer measured ulcer area. RESULTS All patients had complete corneal healing within an average of 4.13 ± 2.32 weeks. Mean ulcer area decreased significantly (P = 0.001) from 16.51% ± 18.56% (1st day) to 8.68% ± 11.25% at the 7th day and to 4.73% ± 10.75% at the 14th day. Compared with day 1, mean ulcer area decreased 60.24% after 7 days (P = 0.001), 54.92% after 14 days (P = 0.059), and 83.00% after 21 days (P = 0.003). Two cases of recurrence (8.0%) were registered. No systemic or local side effects were noticed. CONCLUSIONS The new regenerating agent, Cacicol, represents an effective and safe therapy to treat NK.