Congenital Malformations of the Eye: A Pictorial Review and Clinico-Radiological Correlations.

Congenital malformations of the eye represent a wide and heterogeneous spectrum of abnormalities that may be part of a complex syndrome or be isolated. Ocular malformation severity depends on the timing of the causative event during eye formation, ranging from the complete absence of the eye if injury occurs during the first weeks of gestation, to subtle abnormalities if the cause occurs later on. Knowledge of ocular malformations is crucial to performing a tailored imaging protocol and correctly reporting imaging findings. Together with the ophthalmologic evaluation, imaging may help frame ocular malformations and identify underlying genetic conditions. The purpose of this pictorial review is to describe the imaging features of the main ocular malformations and the related ophthalmologic findings in order to provide a clinico-radiological overview of these abnormalities to the clinical radiologist. Sight is a crucial sense for children to explore the world and relate with their parents from birth. Vision impairment or even blindness secondary to ocular malformations deeply affects children's growth and quality of life.

Long-term follow-up in a pediatric patient with Ligneous Conjunctivitis due to PLG gene mutation in topical plasminogen treatment after successful use of ocular prosthesis for aesthetic rehabilitation: a case report.

BACKGROUND: Ligneous Conjunctivitis (LC) is the most common clinical manifestation of Type I Plasminogen deficiency (T1PD; OMIM# 217090), and it is characterized by the formation of pseudomembranes (due to deposition of fibrin) on the conjunctivae leading to progressive vision loss. In past times, patients with LC were treated with surgery, topical anti-inflammatory, cytostatic agents, and systemic immunosuppressive drugs with limited results (Blood 108:3021-3026, 2006, Ophthalmology 129:955-957, 2022, Surv Ophthalmol 48:369-388, 2003, Blood 131:1301-1310, 2018). The surgery can also trigger the development of membranes, as observed in patients needing ocular prosthesis (Surv Ophthalmol 48:369-388, 2003). Treatment with topical purified plasminogen is used to prevent pseudomembranes formation (Blood 108:3021-3026, 2006, Ophthalmology 129:955-957, 2022). CASE PRESENTATION: We present the case of a sixteen-year-old girl with LC with severe left eye involvement. We reported the clinical conditions of the patient before and after the use of topical plasminogen eye drops and described the treatment schedule allowing the surgical procedure for the pseudomembranes debulking and the subsequent use of ocular prosthesis for aesthetic rehabilitation. CONCLUSIONS: The patient showed a progressive response to the topical plasminogen, with a complete absence of pseudomembrane formation at a twelve-year follow-up, despite using an ocular prosthesis.

Simultaneous transepithelial topographic-guided laser and cross-linking to correct irregular astigmatism in a pediatric patient.

PURPOSE: To evaluate an original approach for treating corneal ectasia and irregular astigmatism secondary to penetrating trauma in a pediatric patient. CASE REPORT: An 11 year old patient had a penetrating trauma in right eye when he was two and the refractive error was +1.50 diopters sphere -6.00 diopters cylinder axis 95°. To correct irregular astigmatism, the patient underwent simultaneous transepithelial topographic-guided laser Central Corneal Remodeling (CCR) and Corneal Cross-linking (CXL) in the attempt to regularize corneal ectasia and to improve the quality of vision. Uncorrected and Corrected Distance Visual Acuity were measured using Efficacy and Safety indexes; objective and subjective qualities of vision were evaluated using respectively corneal morphological irregularity index and National Eye Institute Visual Function questionnaires. CONCLUSIONS: Twelve month follow up suggests that simultaneous CCR and CXL could be effective to improve the quality of vision and to halt the progression of post-traumatic ectasia in pediatric patients.

Rethinking the Management of Optic Pathway Gliomas: A Single Center Experience.

Background: Optic pathway gliomas (OPGs) are rare neoplasms in children with an unpredictable clinical course. Approximately 15% of OPGs occur in patients affected by neurofibromatosis type 1 (NF1): the clinical course of these cases is more indolently than sporadic ones, and NF1 patients less frequently require treatment including surgery. Instead, over 90% of sporadic OPGs require one or more therapeutic approaches. The management of OPG is controversial. They are also characterized by a high risk of morbidity including hypothalamic damage, endocrine deficits, visual deficit and/or neurological impairment. Materials and Methods: In this paper, we evaluated visual and endocrinological outcomes of a population of OPG followed at our center from 2013 to 2021, with a particular emphasis on the role of surgery. Results: Twenty-six patients were included in this study (mean age of 40.7 months). Tumor location on imaging was described by the Dodge classification. Five cases had NF 1. Thirteen cases received biopsy and 13 were partially resected. Histopathology revealed 19 cases of pilocytic astrocytomas, 2 pilomyxoid astrocytoma and 5 ganglioglioma. All the patients required a post-surgical adjuvant treatment according to current indications for low-grade gliomas. Molecular studies (BRAF status and mTOR/pmTOR pathway) have been performed in 24/26 patients, following for the use of target therapy in 11 of these patients. In our study we found that patients underwent biopsy have a better visual and endocrinological outcomes rather than patients with a tumor debulking. The five-year overall survival rate is 98% with a mean follow-up of 60 months. Conclusions: Many children with OPGs survive with a residual tumor. They suffer from chronic diseases such as endocrine dysfunction, visual disturbance, motor deficits and poor quality of life. All patients need comprehensive diagnostic work-up including neuroimaging, clinical evaluations and neuropathology approach; at the same time, they need therapeutic decisions and concepts for the choice of timing and type of neurosurgical intervention, chemotherapy and target therapy as well as surveillance and rehabilitation to maximize survival and overall functional outcomes. Our study showed that minimal invasive surgery with the purpose of molecular characterization of the tumor is desirable to reduce morbidity correlate to surgery.

An epidemiologic analysis of the association between eyelid disorders and ocular motility disorders in pediatric age.

Aim of the study was to assess: (a) the prevalence and type of strabismus, ptosis and eyelid dynamic disorders features, (b) the prevalence of refractive errors, amblyopia and, (c) their association with ocular/systemic syndromes in a cohort of patients. This is a retrospective observational multicenter cohort study. Patients with coexisting ocular motility disorders, comitant and incomitant strabismus, ptosis and dynamic eyelid disorders who have never undergone surgery were enrolled throughout a 3-years a study period. 137 out of 19,089 patients were enrolled, of which 97 with uniocular and 40 with binocular disease. Isolated congenital ptosis was observed in 84 patients. A polymalformative syndrome was present in almost one third of cases, whilst among strabismus type, esotropia was slightly more prevalent. Most patients were hypermetropic. In monocular disease, myopia mainly affected older patients, who were characterized by a worse ptosis margin reflex distance and levator function, and significantly higher astigmatism. Amblyopia occurred in 67.4% of the study sub-population. Of note, in monocular disease this was mild in 25.8%, moderate in 24.2% and severe in 11.3% of cases, whilst in binocular disease it was mild in 25%, moderate in 41.7% and severe in 16.7%. All patients with coexisting eyelid and ocular motility dysfunctions in pediatric age need ophthalmologic and systemic evaluation to accurately assess amblyopia, refractive errors and systemic/ocular disorders.

Analysis of tear film in cystinosis patients treated with topical viscous cysteamine hydrochloride (Cystadrops®).

PURPOSE: The aim of this study was to evaluate in vivo the tear film in infantile nephropathic cystinosis patients with corneal crystals treated with topical viscous cysteamine hydrochloride (Cystadrops®). METHODS: Ten eyes of five patients with nephropathic cystinosis aged from 10 to 35 years were included in this study. The patients were under treatment with viscous cysteamine hydrochloride formulation containing 3.8 mg/mL cysteamine (vCH 0.55%, equivalent to 0.55% CH; Cystadrops®; Recordati rare Diseases, Puteaux, France) to reduce corneal crystal density. Five age and sex matched individuals were randomly selected as control group. Tear osmolarity testing (TearLabTM) was performed to assess the in vivo osmolarity of patients under treatment and compared to control group values. Tear film break-up time (TBUT) and basic tear secretion (Schirmer test) were also assessed. RESULTS: Mean tear osmolarity was 294.8 mOsms/L (±10.4), with a mean absolute difference of 1.85 mOsms/L (±2.13) between the eyes. There was no statistically significant difference between the osmolarity readings of cystinosis and the control group (294.8 ± 10.4 vs 299.4 ± 6.2mOsm/L, respectively; p = 0.39). The mean TBUT was 10.2 ± 0.83 s in the study group versus 10 ± 0.7 s in controls (p = 0.62). The mean Schirmer test score was 9.2 ± 0.83 mm in the patients versus 10.2 ± 0.83 mm in the controls (p = 0.14). CONCLUSIONS: The TearLabTM osmolarity system test showed good reliability and precision in repeated measurements. This is the first report using the TearLab osmolarity system to assess tear film in patients with cystinosis treated with vCH 0.55%. TearLabTM examination showed that the use of vCH 0.55% drops does not determine alterations of the tear film quality.

Comparative analysis of visual outcomes of multifocal and monofocal intraocular lenses in congenital cataract surgery.

PURPOSE: To assess the impact on visual development of multifocal vs monofocal intraocular lenses (IOLs) implantation in children after congenital cataract surgery. SETTING: Ophthalmology Department, Bambino Gesù Children's Hospital, Rome, Italy. DESIGN: Retrospective interventional consecutive case series. METHODS: Records of 56 eyes of 43 pediatric patients who underwent congenital cataract surgery with phacoaspiration and simultaneous implantation of the IOL younger than 1 year were reviewed. Corrected distance visual acuity (CDVA), refractive error, and ocular motility disorders were evaluated at follow-up of greater than 4 years. RESULTS: 32 multifocal (18 unilateral, Group A and 14 bilateral, Group B) and 24 monofocal (12 unilateral, Group C and 12 bilateral, Group D) IOLs were implanted. Mean follow-up was 6.67 years. Mean CDVA of the eyes with multifocal IOLs was 0.75 ± 0.46 logMAR in unilateral cataract surgery and 0.34 ± 0.25 logMAR in bilateral ones; with monofocal IOLs was 0.71 ± 0.52 logMAR in unilateral and 0.53 ± 0.43 logMAR in bilateral ones. No statistically significant difference in the CDVA between Groups A and B and Groups C and D were recorded. Final mean spherical equivalent was -3.88 ± 4.73 diopters (D); in Group A, it was -2.74 ± 4.22 D, in Group C was -1.08 ± 1.45 D, in Group B was -4.82 ± 4.64 D, and in Group D was -6.81 ± 4.61 D. The difference was statistically significant between Groups B and D (P = .01), but not between Groups A and C (P = .14). 26 patients (60.4%) showed postoperative strabismus. Surgical correction occurred more in patients with multifocal IOLs implanted (P = .038). CONCLUSIONS: Multifocal IOLs did not show significant advantages in visual development in children after congenital cataract extraction younger than 1 year when compared with monofocal IOLs.

Treatment of Advanced Coats' Disease With Combination Therapy of Laser Photocoagulation, Intravitreal Ranibizumab, and Sub-Tenon Methylprednisolone Acetate.

PURPOSE: To investigate the efficacy of combination therapy with laser photocoagulation, intravitreal ranibizumab, and sub-Tenon methylprednisolone acetate in patients presenting with advanced Coats' disease. METHODS: This was a retrospective analysis of 16 patients who underwent laser photocoagulation combined with intravitreal ranibizumab and sub-Tenon methylprednisolone acetate between 2008 and 2017. The primary outcome was anatomic success and the secondary outcomes were globe preservation and final visual acuity. RESULTS: The average age at surgery was 5.12 ± 2.7 years (range: 3 to 10 years). The mean follow-up time was 45.43 ± 29.01 months (range: 12 to 108 months). Of the 16 patients (16 eyes) reviewed, 6 patients had stage 3A and 10 patients had stage 3B Coats' disease. The mean number of applications was 10 (range: 4 to 18). Globe preservation was achieved in all patients. Final visual acuity outcomes were satisfactory: 20/20 to 20/50 in 2 patients, 20/60 to 20/100 in 1 patient, and 20/200 or worse in 13 patients. CONCLUSIONS: Intravitreal ranibizumab used in combination with laser photocoagulation and sub-Tenon methylprednisolone acetate could be an effective treatment option for patients with advanced Coats' disease. The combined therapy achieved anatomical success, globe preservation, and reasonable visual acuity outcomes. [J Pediatr Ophthalmol Strabismus. 2022;59(3):187-191.].

Keratoconus in Children: A Literature Review.

PURPOSE: This review discusses the main aspects of pediatric keratoconus (KC) based on the current evidence to propose a guideline for helping early diagnosis and improving efficacy in treatment. METHODS: This literature review was performed using PubMed, Ovid, and Elsevier databases. For the database search, the primary entered term included "pediatric keratoconus," connected to descriptors such as "keratoconus," "screening," "corneal cross-linking" (CXL), and "keratoplasty." Peer-reviewed and scholarly resources including original scientific articles and review articles were included. RESULTS: The prevalence of KC changes among populations. The greatest incidence has been reported in Middle-Eastern populations, an estimate of incidence of 1/2,000 individuals per year. Scheimpflug imaging, optical coherence tomography, and slit-scan tomography are commonly used to detect early diagnosis. Epithelium-off CXL is the treatment that should be discussed as soon as there is evidence for disease progression. Actually, penetrating keratoplasty represents the more common technique of pediatric keratoplasty; however, deep anterior lamellar keratoplasty probably seems as the best surgical option because of healthy endothelium. Options to increase visual acuity thereafter include contact lens fitting and corneal implants. CONCLUSIONS: The review of the literature confirms that KC in children is more aggressive than that in adults. In the attempt to preserve a good visual acuity, guidelines for improving early diagnosis and appropriate treatment seem crucial.

Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding.

Retinoblastoma (RB) is the most common tumor of the eye in early childhood. Although recent advances in conservative treatment have greatly improved the visual outcome, local tumor control remains difficult in the presence of massive vitreous seeding. Traditional biopsy has long been considered unsafe in RB, due to the risk of extraocular spread. Thus, the identification of new biomarkers is crucial to design safer diagnostic and more effective therapeutic approaches. Exosomes, membrane-derived nanovesicles that are secreted abundantly by aggressive tumor cells and that can be isolated from several biological fluids, represent an interesting alternative for the detection of tumor-associated biomarkers. In this study, we defined the protein signature of exosomes released by RB tumors (RBT) and vitreous seeding (RBVS) primary cell lines by high resolution mass spectrometry. A total of 5666 proteins were identified. Among these, 5223 and 3637 were expressed in exosomes RBT and one RBVS group, respectively. Gene enrichment analysis of exclusively and differentially expressed proteins and network analysis identified in RBVS exosomes upregulated proteins specifically related to invasion and metastasis, such as proteins involved in extracellular matrix (ECM) remodeling and interaction, resistance to anoikis and the metabolism/catabolism of glucose and amino acids.

Ocular manifestations and viral shedding in tears of pediatric patients with coronavirus disease 2019: a preliminary report.

PURPOSE: To evaluate ocular manifestations and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) prevalence in the tears of children with coronavirus disease 2019 (COVID-19). METHODS: A total of 27 pediatric patients with confirmed COVID-19 infection hospitalized from March 16 to April 15, 2020, at the Bambino Gesù Children's Hospital were enrolled in the study. At admission, all patients showed ocular manifestations. Reverse transcriptase-polymerase chain reaction from nasopharyngeal and conjunctival swabs were performed every 2-3 days before discharge. RESULTS: Of the 27 patients, 4 (15%) were asymptomatic, 15 (56%) showed respiratory symptoms, and 8 (30%) had gastrointestinal symptoms. At admission, nasopharyngeal swabs were positive for COVID-19 in all patients; on the second swabs, 7 children (26%) tested negative, and 20 remained positive for COVID-19. Ocular manifestations consistent with mild viral conjunctivitis were observed in 4 patients (15%). At first conjunctival swab, 3 patients (11%), 1 symptomatic and 2 asymptomatic for ocular infection, had positive findings for COVID-19; 2 became negative on the second test and 1 on the third. CONCLUSIONS: In our study cohort, ocular manifestations of COVID-19 seem to have had a milder clinical course in pediatric patients than in adults. Despite the low prevalence and rapid regression of viral presence in the conjunctiva, SARS-CoV-2 transmission through tears may be possible, even in patients without apparent ocular involvement.

Iontophoretic Transepithelial Collagen Cross-Linking Versus Epithelium-Off Collagen Cross-Linking in Pediatric Patients: 3-Year Follow-Up.

PURPOSE: To compare 3-year iontophoretic transepithelial corneal cross-linking (I-ON CXL) outcomes with epithelium-off collagen cross-linking (epi-off CXL) in pediatric patients. METHODS: Forty eyes of 28 consecutive pediatric patients [mean age 14.3 ± 2.5 (SD) years; range, 9-18 years] with keratoconus were evaluated. Twenty eyes of 15 patients underwent I-ON and 20 eyes of 13 patients epi-off CXL. Mean corrected distance visual acuity, spherical equivalent, maximum keratometry (Kmax), posterior elevation of the thinnest point, and thickness of the thinnest point were evaluated. The Student t test was used to compare baseline and postoperative data. Keratoconus progression as a function of preoperative Kmax and cone location was evaluated. RESULTS: At 36 months, corrected distance visual acuity statistically improved (from 0.18 ± 0.1 to 0.10 ± 0.1 logarithm of the minimum angle of resolution) in epi-off CXL, whereas spherical equivalent and posterior elevation of the thinnest point did not significantly change. Mean Kmax increased from the baseline +0.8 diopters (D) in epi-off and +2.9D in I-ON. In both groups, the thinnest point decreased. Keratoconus progression, defined by an increase of Kmax reading of the anterior corneal surface of at least 1.00D, occurred in 25% of epi-off and 50% of I-ON CXL over the 3-year period. Kmax value in I-ON, and cone location in both groups, seemed to be factors influencing the disease progression. CONCLUSIONS: In pediatric patients, 3 years after treatment, epi-off CXL halted keratoconus progression in 75% of eyes, whereas I-ON CXL seemed to slow down keratoconus progression in 50% of eyes, mainly in those with highest Kmax and paracentral cone.

Refractive outcome of keratoconus treated by big-bubble deep anterior lamellar keratoplasty in pediatric patients: two-year follow-up comparison between mechanical trephine and femtosecond laser assisted techniques.

BACKGROUND: To evaluate refractive outcome 24 months after Deep Anterior Lamellar Keratoplasty (DALK) in pediatric patients by comparing results achieved using mechanical trephine and femtosecond laser. METHODS: Twenty eyes of 20 patients affected by keratoconus were evaluated. To perform big-bubble DALK, 10 eyes (Group 1; mean age 11.2 ± 2.2 years) were subjected to the Hessburg-Barron mechanical trephine and the remaining 10 eyes (Group 2; mean age 11.3 ± 3.1 years) to a 150 kHz femtosecond laser that performed mushroom incisions. Preoperative thinnest point in the corneal thickness map and K readings were measured by the Sirius Scheimpflug camera. We also evaluated corrected distance visual acuity (CDVA) as logMAR value using spectacles, spherical equivalent and refractive astigmatism. RESULTS: Mean preoperative thinnest point and pre- and post-operative K readings did not show significant difference (P > 0.05) between the two groups. CDVA, spherical equivalent and refractive astigmatism were respectively, 0.14 ± 0.08 logMAR and 0.13 ± 0.10 logMAR (P = 0.8), - 4.2 ± 1.1 D and - 2.8 ± 1.2 D (P = 0.03), 4.4 ± 2.0 D and 3.6 ± 1.2 D (P = 0.4) in Groups 1 and 2. All DALK procedures were uneventful. CONCLUSION: Our findings suggest that femtosecond laser compared to mechanical trephine could significantly reduce the spherical equivalent amount in pediatric big-bubble DALK.

Treatment of homozygous familial hypercholesterolaemia in paediatric patients: A monocentric experience.

Background Homozygous familial hypercholesterolaemia is a rare life-threatening disease characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) concentrations and accelerated atherosclerosis. The presence of double gene defects in the LDL-Receptor, either the same defect (homozygous) or two different LDL-raising mutations (compound heterozygotes) or other variants, identify the homozygous phenotype (HopFH). Apheresis is a procedure in which plasma is separated from red blood cells before the physical removal of LDL-C or the LDL-C is directly removed from whole blood. It is currently the treatment of choice for patients with HopFH whose LDL-C levels are not able to be reduced to target levels with conventional lipid-lowering drug therapy. Design The aim of this study is to report a cohort of six paediatric patients and to evaluate the long term efficacy of combined medical therapy and LDL-apheresis on LDL-C reduction. Methods We collected data from six children with confirmed diagnosis of HopFH (two females and four males; age range at diagnosis 3-8 years, mean 6 ± 1 years) from a single clinical hospital in Italy from 2007 to 2017. Results Clinical manifestations and outcomes may greatly vary in children with HopFH. Medical therapy and LDL-apheresis for the severe form should be started promptly in order to prevent cardiovascular disease. Conclusions Lipoprotein apheresis is a very important tool in managing patients with HopFH at high risk of cardiovascular disease. Based on our experience and the literature data, the method is feasible in very young children, efficient regarding biological results and cardiac events, and safe with minor side-effects and technical problems. We advise treating homozygous and compound heterozygous children as soon as possible.

Four years of corneal keratoplasty in Italian paediatric patients: indications and clinical outcomes.

PURPOSE: The purpose was to evaluate indications and clinical outcomes in paediatric corneal keratoplasty. METHODS: Fifty-four eyes of 43 patients who underwent corneal keratoplasty from the 1st of January 2010 through the 31st of December 2013 at the Bambino Gesù Children's Hospital in Rome, Italy, were retrospectively evaluated. To assess the effect of age on graft failure rate, the recipient age was considered as a dichotomous variable (≤5 or >5 years) and a 2X2 table was developed, using the chi-square test for testing the statistical significance. Furthermore, two separate subgroup analyses were conducted on patients of ≤5 years and those of >5 years, to evaluate the effect of penetrating keratoplasty (PK) or deep anterior lamellar keratoplasty (DALK) on the graft failure rate. The level of statistical significance was set at p < 0.05 RESULTS: Mean recipient age was 8.9 ± 5.7 [SD] years. Mean follow-up time was 22.8 months. Main preoperative diagnoses were keratoconus (37 %) and congenital glaucoma (20 %). Patients ≤5 years showed a higher percentage of graft failure (p = 0.0008). PK and DALK did not show statistically significant differences regarding the graft failure in both subgroups (p = 0.15 for ≤5 years group and p = 0.27 for >5 years group, respectively). However, across groups DALK provided a lower rate of graft failure. CONCLUSIONS: Our findings suggest that children older than 5 years show a significantly better graft outcome and that DALK seems to offer greatest benefits in terms of failure risk in paediatric patients.

Novel plasminogen and hyaluronate sodium eye drop formulation for a patient with ligneous conjunctivitis.

PURPOSE: The development, analysis, and first clinical use of a novel eye drop formulation of plasminogen and hyaluronate sodium for the treatment of a patient with ligneous conjunctivitis (LC) are described. SUMMARY: LC is a chronic inflammatory disorder of the eye that can in rare cases lead to corneal involvement and subsequent blindness. Topically administered plasminogen is an effective treatment for LC; however, the lack of a specific and validated formulation of plasminogen for topical treatment can constitute a gap in the quality of care. A novel formulation of plasminogen and hyaluronate sodium for the treatment of LC was developed by combining commercially available products. Through a series of tests, including microbiological, viscosity, and pH analyses, the novel eye drop formulation was demonstrated to have constant activity (3.3 IU/mL or greater), to be microbiologically stable (i.e., sterile), and to be safe enough for daily administration. The first clinical application of the novel eye drop formulation was in the case of a nine-year-old girl with LC affecting both eyes. Initially, the girl's parents administered two drops every three hours to the left eye each day while the girl was awake. On examination after 30 days of daily use of the eye drop formulation, the patient was found to have a clear cornea and no membrane development on the conjunctiva; the formulation was subsequently administered in both eyes, with positive results. CONCLUSION: A new formulation of plasminogen plus hyaluronate sodium was developed, tested, and used successfully in a girl with LC.

The Big-Bubble Full Femtosecond Laser-Assisted Technique in Deep Anterior Lamellar Keratoplasty.

PURPOSE: To describe the big-bubble full femtosecond laser-assisted (BBFF) technique, which could be helpful in standardizing the big-bubble technique in deep anterior lamellar keratoplasty (DALK). METHODS: Ten eyes of 10 consecutive patients affected by keratoconus underwent the BBFF technique using the 150-kHz IntraLase femtosecond laser (Intra-Lase FS Laser; Abbott Medical Optics, Inc., Santa Ana, CA). A 9-mm diameter metal mask with a single fissure 0.7 mm wide oriented at the 12-o'clock position was positioned into the cone, over the laser glass. The laser performed a ring lamellar cut (internal diameter = 3 mm; external diameter = 8 mm) 100 µm above the thinnest point, with the photodisruption effectively occurring only in the corneal stroma corresponding to the fissure to create a deep stromal channel; subsequently, an anterior side cut created an arcuate incision, from the corneal surface to the deep stromal channel on the mask's opening site. The mask was removed and the laser performed a full lamellar cut 200 µm above the thinnest point to create a lamella. After the removal of the lamella, the air needle was inserted into the stromal channel and air was injected to achieve a big bubble. RESULTS: The big bubble was achieved in 9 eyes (all type 1 bubbles) and all procedures were completed as DALK. CONCLUSIONS: Preliminary results suggest that the BBFF technique could help in standardizing the big-bubble technique in DALK, reducing the "learning curve" for surgeons who approach this technique and the risks of intraoperative complications.