New ZNF469 Mutations in Spanish Siblings With Brittle Cornea Syndrome.

PURPOSE: The aim of this study was to describe the clinical, tomographic, and genetic findings of 2 Spanish siblings with brittle cornea syndrome and report a new mutation of gene ZNF469 implicated in the development of this disorder. METHODS: In this study, 2 male siblings who had been diagnosed with brittle cornea syndrome underwent ophthalmologic and genetic assessment. RESULTS: A novel homozygous deletion c.2972del, p.(Pro991Hisfs62) in the ZNF469 gene was identified in a Spanish family. CONCLUSIONS: This is the first report of a ZNF469 mutation in a Spanish family causing brittle cornea syndrome. The discovery of this new mutation amplifies the spectrum of ZNF469 variants implicated in this syndrome.

Correction: Bacterial nanocellulose as a corneal bandage material: a comparison with amniotic membrane.

Correction for 'Bacterial nanocellulose as a corneal bandage material: a comparison with amniotic membrane' by Irene Anton-Sales et al., Biomater. Sci., 2020, 8, 2921-2930, DOI: .

Bacterial nanocellulose as a corneal bandage material: a comparison with amniotic membrane.

Corneal trauma and ulcerations are leading causes of corneal blindness around the world. These lesions require attentive medical monitoring since improper healing or infection has serious consequences in vision and quality of life. Amniotic membrane grafts represent the common solution to treat severe corneal wounds. However, amniotic membrane's availability remains limited by the dependency on donor tissues, its high price and short shelf life. Consequently, there is an active quest for biomaterials to treat injured corneal tissues. Nanocellulose synthetized by bacteria (BNC) is an emergent biopolymer with vast clinical potential for skin tissue regeneration. BNC also exhibits appealing characteristics to act as an alternative corneal bandage such as; high liquid holding capacity, biocompatibility, flexibility, natural - but animal free-origin and a myriad of functionalization opportunities. Here, we present an initial study aiming at testing the suitability of BNC as corneal bandage regarding preclinical requirements and using amniotic membrane as a benchmark. Bacterial nanocellulose exhibits higher mechanical resistance to sutures and slightly longer stability under in vitro and ex vivo simulated physiological conditions than amniotic membrane. Additionally, bacterial nanocellulose offers good conformability to the shape of the eye globe and easy manipulation in medical settings. These excellent attributes accompanied by the facts that bacterial nanocellulose is stable at room temperature for long periods, can be heat-sterilized and is easy to produce, reinforce the potential of bacterial nanocellulose as a more accessible ocular surface bandage.

Osteo-odonto-, Tibial bone and Boston keratoprosthesis in clinically comparable cases of chemical injury and autoimmune disease.

PURPOSE: To compare anatomical and functional results between three types of keratoprosthesis (KPro) in chemical injury and autoimmune disease. METHODS: 70 clinically comparable cases were included as follows: Boston KPro Type 1 25 eyes, osteo-odonto-keratoprosthesis (OOKP) 23 eyes, Tibial bone KPro 22 eyes. Survival times for anatomical and functional success were evaluated with Kaplan-Meier estimations and Log-rank tests. KPro exchange was considered a complication, not as failure. RESULTS: Prosthesis retention in chemical injury group at 5 years was 86% for OOKP, 100% for Tibial bone KPro, and 65% for Boston KPro (p = 0.09), while in the autoimmune disease group it was 66% for Tibial bone KPro and 50% for Boston KPro (p = 0.19; OOKP only one case). Functional success in the chemical injury group at 5 years was 86% for OOKP, 84% for Tibial bone KPro and 71% for Boston KPro (p = 0.38), while in the autoimmune group, it was 44% for Tibial bone KPro and 15% for Boston KPro (p = 0.15; OOKP only one case). The post-operative complications in all groups were: retinal detachment, vitreous hemorrhage, endophthalmitis, retro-prosthetic membrane, uncontrolled glaucoma, the last two being more common in Boston KPro. CONCLUSIONS: For both diagnoses, chemical injury and autoimmune diseases, there was a tendency for better long-term anatomical and functional results with Tibial bone KPro followed by OOKP and Boston KPro Type 1. However, these results were not statistically significant.

Comparison of long-term results between osteo-odonto-keratoprosthesis and tibial bone keratoprosthesis.

PURPOSE: To compare the anatomical and the functional results between osteo-odonto-keratoprosthesis (OOKP) and keratoprosthesis using tibial bone autograft (Tibial bone KPro). METHODS: We reviewed the charts of 258 patients; 145 had OOKP whereas 113 had Tibial bone KPro implanted. Functional success was defined as best corrected visual acuity ≥0.05 on decimal scale and anatomical success as retention of the keratoprosthesis lamina. Kaplan-Meier survival curves were calculated for anatomical and functional survival as well as to estimate the probability of post-op complications. RESULTS: The anatomical survival for both KPro groups was not significantly different and was estimated as 67% for OOKP and 54% for Tibial bone KPro at 10 years after surgery. There was also no difference found after subdividing for primary diagnosis groups such as chemical injury, thermal burn, trachoma and all autoimmune cases combined. Estimated functional survival at 10 years post-surgery was 49% for OOKP and 25% for Tibial bone KPro, which was significantly different. The probability of patients with Tibial bone KPro developing one or more post-operative complications at 10 years after surgery (65%) was significantly higher than those with OOKP (40%). Mucous membrane necrosis and retroprosthetic membrane formation were more common in Tibial bone KPro than OOKP. CONCLUSION: Both types of autologous biological KPro, OOKP and Tibial bone KPro, had statistically similar rate of keratoprosthesis extrusion. Although functional success rate was significantly higher in OOKP, it may have been influenced by a better visual potential in the patients in this group.

Femtosecond laser-assisted laser in situ keratomileusis versus photorefractive keratectomy: Effect on ocular surface condition.

PURPOSE: To compare ocular surface characteristics in eyes after femtosecond laser-assisted laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK). SETTING: Centro de Oftalmologia Barraquer, Barcelona, Spain. DESIGN: Prospective comparative observational study. METHODS: Patients with myopia who had femtosecond laser-assisted LASIK or PRK were included. Tear osmolarity, the Ocular Surface Disease Index questionnaire, Schirmer I, corneal sensitivity, tear breakup time (TBUT), and corneal fluorescein staining were evaluated preoperatively and 3, 6, and 12 months postoperatively. The Wilcoxon signed-rank test was used for temporal intragroup analysis, and the Mann-Whitney U test was used for intergroup comparisons. RESULTS: The study comprised 44 patients (44 eyes) with myopia. Comparison of the parameters between the femtosecond laser-assisted LASIK group (22 eyes) and the PRK group (22 eyes) showed a similar temporal progression postoperatively. Compared with the preoperative evaluation, corneal sensitivity decreased after 3 months (P = .002 and P = .02, respectively) and 6 months (P = .03 and P = .04, respectively). The TBUT reached the highest mean value after 12 months (P = .01 and P = .04, respectively), and tear osmolarity was slightly increased after 1 year, although the mean values remained within the normal range (P = .01 and P = .04, respectively). The only difference between the 2 groups was lower corneal sensitivity in the femtosecond laser-assisted LASIK group after 3 months (P = .02). The ocular surface condition could be considered clinically unaltered after 1 year in both groups. CONCLUSION: Femtosecond laser-assisted LASIK and PRK techniques seemed to be safe for the ocular surface condition and to have a similar effect on it.

Osteokeratoprosthesis Using Tibial Bone: Surgical Technique and Outcomes.

PURPOSE: To analyze the anatomical and functional results of keratoprosthesis using tibial bone autograft. METHODS: We reviewed 113 charts of patients who underwent tibial bone osteokeratoprothesis implantation at the Centro de Oftalmologia Barraquer. Kaplan-Meier survival curves with 95% confidence interval were calculated for functional success, defined as best corrected visual acuity (BCVA) ≥0.05 on the decimal scale, and for anatomical success, defined as retention of the keratoprosthesis lamina. Multivariate analysis was used to test the impact of clinical factors on anatomical and functional survival rates. RESULTS: Based on Kaplan-Meier analyses, tibial bone keratoprosthesis 5-year and 10-year anatomical survival rates were 69.5% and 53.5%, respectively. Functional survival rate at 5 years was 33% and at 10 years was 19.2%. Considering primary diagnosis, chemical burn had better anatomical and functional survival rates than autoimmune or infectious diseases. Patient age did not have a significant effect on keratoprosthesis survival rates. About 48.7% of the patients who underwent surgery had complications: keratoprosthesis extrusion, glaucoma, retinal detachment and buccal mucosa necrosis were the most frequent ones. CONCLUSION: Half of the patients with tibial bone KPro had retained the keratoprosthesis after 10 years post-surgery and one-fifth of them had visual acuity of 0.05 or better at the same period. Considering that these patients have no other way to recover their vision either because they have no canine tooth or their buccal or dental conditions are not adequate for OOKP, this modified surgery is their only hope.

Clinical utility of objective tests for dry eye disease: variability over time and implications for clinical trials and disease management.

PURPOSE: To evaluate the efficacy of commonly used biomarkers in dry eye disease management in a longitudinal observational case series study followed by an interventional study in a subset of subjects treated with cyclosporine A (0.05%). METHODS: Bilateral tear osmolarity, Schirmer, tear film breakup time (TBUT), staining, meibomian grading, and Ocular Surface Disease Index were measured for a period of 3 consecutive months in participants recruited from a clinic-based population at 2 study sites. Fifty-two subjects completed the study (n = 16 mild/moderate, n = 36 severe; age, 47.1 ± 16.1 years). After the 3-month observation period, severe dry eye patients were prescribed topical cyclosporine A and evaluated for an additional 3 months. RESULTS: Tear osmolarity (8.7 ± 6.3%) exhibited significantly less variability over a 3-month period than corneal staining (12.2 ± 8.8%, P = 0.040), conjunctival staining (14.8 ± 8.9%, P = 0.002), and meibomian grading (14.3 ± 8.8%, P < 0.0001) across the entire patient population. Osmolarity also demonstrated less variation than TBUT (11.7 ± 9.0%, P = 0.059), Schirmer tests (10.7 ± 9.2%, P = 0.67), and Ocular Surface Disease Index (9.3 ± 7.8%, P = 0.94), although the differences were not significant. Variation in osmolarity was less for mild dry eye patients (5.9 ± 3.1%) than severe dry eye patients (10.0 ± 6.9%, P = 0.038). After treatment, average osmolarity and variability were lowered from 341 ± 18 mOsm/L to 307 ± 8 mOsm/L (P < 0.0001, n = 10). A downward trend in symptoms followed changes in osmolarity, declining from 44 ± 17 mOsm/L to 38 ± 18 mOsm/L (P = 0.35). None of the other signs demonstrated a change after treatment. CONCLUSIONS: Over a 3-month period, tear film osmolarity was found to have the lowest variability among commonly used signs of dry eye disease. Reductions in osmolarity preceded changes in symptoms during therapy.

The role of visual evoked potential and electroretinography in the preoperative assessment of osteo-keratoprosthesis or osteo-odonto-keratoprosthesis surgery.

PURPOSE: To determine the value of electroretinography (ERG) and visual evoked potential (VEP) in predicting visual outcome in patients undergoing osteo-keratoprosthesis (OKP) or osteo-odonto-keratoprosthesis (OOKP) surgery. METHODS: We performed a retrospective cohort study of 143 eyes in 101 patients who underwent OKP or OOKP surgery. The subjects underwent ERG, VEP testing or both up to 6 months prior to surgery. The ERG and VEP results were classified into four categories based on wave amplitude, latency and configuration. The main outcome was the maximum best-corrected visual acuity (maxBCVA) reached at any time postoperatively. RESULTS: One hundred thirty-four cases had undergone preoperative ERG, 82 VEP and 73 both examinations. The sensitivities of ERG and VEP to detect maxBCVA≥0.05 were 68.5% and 87%, respectively, while the specificity was 63.2% for ERG and 47.4% for VEP. The maxBCVA was significantly better in patients with normal ERG (p=0.033) and those with normal VEP (p=0.048), once having defined appropriate normal and abnormal cut-off levels. When comparing fellow eyes in patients who underwent surgery in both eyes, maxBCVA was better in the eyes that had better VEP results (p=0.013). CONCLUSION: Eyes demonstrating normal ERG or VEP achieved better visual outcome than those with abnormal results. In addition, VEP proved instrumental in determining the eye with the best prognosis when comparing both eyes of a given patient.

Impact of clinical factors on the long-term functional and anatomic outcomes of osteo-odonto-keratoprosthesis and tibial bone keratoprosthesis.

PURPOSE: To report the long-term functional and anatomic outcomes of osteo-odonto-keratoprosthesis and tibial bone keratoprosthesis; to analyze the influence of clinical factors, such as surgical technique, primary diagnosis, age, and postoperative complications, on the final outcome. DESIGN: Retrospective cohort study. METHODS: setting: Centro de Oftalmología Barraquer, between 1974 and 2005. PARTICIPANTS: Two hundred twenty-seven patients. intervention: Biological keratoprosthesis using osteo-odonto-keratoprosthesis or tibial bone keratoprosthesis. main outcome measures: Functional survival with success defined as best-corrected visual acuity ≥0.05; anatomic survival with success defined as retention of the keratoprosthesis lamina. RESULTS: Osteo-odonto-keratoprosthesis and tibial bone keratoprosthesis have comparable anatomic survival at 5 and 10 years of follow-up, but osteo-odonto-keratoprosthesis has a significantly better functional success than tibial bone keratoprosthesis at the same time periods. Among the primary diagnoses, Stevens-Johnson syndrome, chemical burn, and trachoma have generally good functional and anatomic outcomes and the least favorable prognosis is for ocular cicatricial pemphigoid. Younger patients fared better than those in older age groups. The most frequent complications were extrusion (28%), retinal detachment (16%), and uncontrolled glaucoma (11%). The glaucoma group had the best anatomic success but the worst functional results, only exceeded by the retinal detachment group in terms of functional outcome. CONCLUSION: Clinical factors, such as surgical technique, primary diagnosis, age, and postoperative complications, can affect the long-term anatomic and functional successes of biological keratoprosthesis. Knowledge about the impact of each of these factors on survival can help surgeons determine the best approach in every particular case.

Long-term functional and anatomical results of osteo- and osteoodonto-keratoprosthesis.

PURPOSE: To analyse the functional and anatomical results of keratoprosthesis using tooth and tibial autograft. METHODS: We reviewed 227 charts of patients that underwent osteo-keratoprosthesis (OKP) (n = 82) or osteo-odonto-keratoprosthesis (OOKP) (n = 145) at the Centro de Oftalmología Barraquer. Mean follow-up time was 8.4 years for OOKP and 3.5 years for OKP. Kaplan-Meier survival curves with 95% confidence interval (CI) were calculated for functional success, defined as BCVA >0.05. Anatomical success was defined as retention of the keratoprosthesis lamina. Visual Acuity by Time (VAT) Index with 95% CI was calculated for up to 2 years post-OKP and up to 6 years post-OOKP. Maximum visual acuity ever reached after the last step of the implantation of the keratoprosthesis was used as an indicator for the potential of the retina. RESULTS: Based on Kaplan-Meier analyses, 10-year anatomical survival was 66% (CI 57-76) for OOKP and 47% (CI 27-67) for OKP. Two-year functional survival was 63% (CI 55-71) for OOKP and 49% (CI 37-60) for OKP, and 10-year functional survival was 38% (CI 29-48) for OOKP and 17% (CI 5-28) for OKP. Multivariate analysis showed that neither surgical technique (OOKP or OKP), primary diagnosis nor age had a significant influence on the functional survival. However, a high maximum visual acuity ever reached post-op decreased the risk for functional failure. According to the VAT Index calculations, mean BCVA 2 years after OOKP was 0.33 (CI 0.28-0.41) and after OKP was 0.28 (CI 0.20-0.36). CONCLUSION: Although we found a tendency that OOKP had better anatomical results than OKP, this difference was not statistically significant up to 10 years post-op. Functional results for both techniques were not significantly different at the 2-year follow-up, but at 10 years they were. However, this difference was influenced by the retinal potential and not by the technique itself.