Correlation of anterior segment optical coherence tomography and ultrasound biomicroscopy in congenital corneal opacity.

PURPOSE: To investigate the correlation between swept-source anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) in congenital corneal opacity (CCO). METHODS: All children with unilateral or bilateral congenital corneal opacities who underwent examination under anesthesia (EUA) and anterior segment optical coherence tomography (AS-OCT) imaging from January 1, 2022, to December 31, 2022, were included. Main outcome measures were corneal and anterior segment evaluation and correlation of UBM and AS-OCT findings. RESULTS: A total of 22 eyes of 15 patients were imaged using both technologies. The age at first EUA ranged from 11 days to 4 years. Different phenotypes were classified based on the clinical examination, UBM, and AS-OCT findings. Fourteen eyes were diagnosed with Peters anomaly, congenital corneal staphyloma was observed in 4 eyes, 2 eyes had coloboma, 1 eye had peripheral sclerocornea, and 1 eye was diagnosed with congenital primary aphakia. AS-OCT and UBM findings were closely correlated in 18 of 22 eyes (82%) but AS-OCT failed to provide detailed information in 4 eyes (18%) where UBM revealed more details. CONCLUSIONS: Although AS-OCT offers valuable preliminary data for initial assessment and counseling, it may not consistently provide precise assessments in all cases. Therefore, UBM should be considered for definitive evaluation.

Optical coherence tomography angiography in herpetic leucoma.

BACKGROUND: Herpes simplex virus (HSV) keratitis remains a leading infectious cause of blindness worldwide. Although all forms of HSV keratitis are commonly recurrent, the risk is greatest in stromal keratitis, which is the most likely to result in corneal scarring, thinning, and neovascularization. Recent studies showed the ability of Optical Coherence Tomography Angiography (OCTA) to detect and study vascular abnormalities in the anterior segment, including abnormal corneal vessels. This study intends to investigate the potential of OCTA device to image and describe quantitatively the vascularization in eyes diagnosed with herpetic leucoma and to discuss and review the usefulness of this technique in this pathology. METHODS: A Cross-sectional study was made, including 17 eyes of 15 patients with leucoma secondary to herpetic keratitis. All eyes underwent anterior segment Slit-Lamp photography (SLP), and OCTA with en-face, b-scans and c-scans imaging. The vessel density (VD) was analyzed in the inferior, nasal and temporal corneal margin in all patients, and in the central area, in eyes with central corneal neovascularization (CoNV). The measurements were calculated after binarization with ImageJ software, using OCTA scans with 6 × 6 mm in a depth of 800 µm. RESULTS: Patients included had a mean age 53.267 ± 21.542 (years ± SD). The mean total vessel area was 50.907% ± 3.435%. VD was higher in the nasal quadrant (51.156% ± 4.276%) but there were no significant differences between the three analyzed areas (p = 0.940). OCTA was able to identify abnormal vessels when SLP apparently showed no abnormal vessels; OCTA was able to distinguish between larger and smaller vessels even in central cornea; OCTA scans allowed the investigation of several corneal planes and the relation of them with clinical findings. CONCLUSIONS: OCTA can be useful in both qualitative and quantitative follow-up of patients and may become a non-invasive alternative to objectively monitor treatment response in eyes with corneal vascularization due to herpetic infection.

Polluted Air Exposure Compromises Corneal Immunity and Exacerbates Inflammation in Acute Herpes Simplex Keratitis.

Air pollution is a serious environmental issue worldwide in developing countries' megacities, affecting the population's health, including the ocular surface, by predisposing or exacerbating other ocular diseases. Herpes simplex keratitis (HSK) is caused by the herpes simplex virus type 1 (HSV-1). The primary or recurring infection in the ocular site causes progressive corneal scarring that may result in visual impairment. The present study was designed to study the immunopathological changes of acute HSK under urban polluted air, using the acute HSK model combined with an experimental urban polluted air exposure from Buenos Aires City. We evaluated the corneal clinical outcomes, viral DNA and pro-inflammatory cytokines by RT-PCR and ELISA assays, respectively. Then, we determined the innate and adaptive immune responses in both cornea and local lymph nodes after HSV-1 corneal by immunofluorescence staining and flow cytometry. Our results showed that mice exposed to polluted air develop a severe form of HSK with increased corneal opacity, neovascularization, HSV-1 DNA and production of TNF-α, IL-1ß, IFN-γ, and CCL2. A high number of corneal resident immune cells, including activated dendritic cells, was observed in mice exposed to polluted air; with a further significant influx of bone marrow-derived cells including GR1+ cells (neutrophils and inflammatory monocytes), CD11c+ cells (dendritic cells), and CD3+ (T cells) during acute corneal HSK. Moreover, mice exposed to polluted air showed a predominant Th1 type T cell response over Tregs in local lymph nodes during acute HSK with decreased corneal Tregs. These findings provide strong evidence that urban polluted air might trigger a local imbalance of innate and adaptive immune responses that exacerbate HSK severity. Taking this study into account, urban air pollution should be considered a key factor in developing ocular inflammatory diseases.

Tuck In Femtosecond Laser Assisted Anterior Lamellar Keratoplasty (T-FALK) for the Management of Superficial Anterior Corneal Scars-A Modified Technique.

PURPOSE: To report a modified sutureless and glue-less technique, termed tuck in femtosecond laser assisted anterior lamellar keratoplasty (T-FALK), and to achieve a good graft-host junction apposition. METHODS: This is a prospective interventional case series of 15 eyes of 15 patients who underwent T-FALK. Depth of the anterior corneal scar was assessed using anterior segment optical coherence tomography (ASOCT). The donor and recipient lenticules were prepared using femtosecond laser. After removing the recipient anterior scarred lenticule, the transparent donor lenticule was positioned on the recipient bed and margins tucked in under the recipient cornea. A bandage contact lens was applied for 3 weeks. Postoperatively, topical antibiotic and steroid combination eye drops were given, and the assessment of healing of the graft-host junction was done using ASOCT. RESULTS: A total of 15 patients (8 men and 7 women) underwent T-FALK. Six patients had superficial corneal opacities after healed microbial keratitis, 5 patients had spheroidal corneal degeneration, 3 patients had Salzman nodular degeneration, and 1 patient had vortex keratopathy. No intraoperative or postoperative complications were noted during T-FALK. All patients had good graft-host junction apposition postoperatively, as demonstrated by ASOCT. CONCLUSIONS: Sutureless and glue-less T-FALK can be the best way ahead for management of superficial anterior corneal scars with good visual outcome.

A systematic review of ultrasound biomicroscopy use in pediatric ophthalmology.

Ultrasound biomicroscopy (UBM) is the only available option for noninvasive, high-resolution imaging of the intricate iridociliary complex, and for anterior segment imaging with corneal haze or opacity. While these unique features render UBM essential for specific types of trauma, congenital anomalies, and anterior segment tumors, UBM imaging has found clinical utility in a broad spectrum of diseases for structural assessments not limited to the anterior intraocular anatomy, but also for eyelid and orbit anatomy. This imaging tool has a very specific niche in the pediatric population where anterior segment disease can be accompanied by corneal opacity or clouding, and anomalies posterior to the iris may be present. Pediatric patients present additional diagnostic challenges. They are often unable to offer detailed histories or fully cooperate with examination, thus amplifying the need for high-resolution imaging. This purpose of this systematic review is to identify and synthesize the body of literature involving use of UBM to describe, evaluate, diagnose, or optimize treatment of pediatric ocular disease. The collated peer-reviewed research details the utility of this imaging modality, clarifies the structures and diseases most relevant for this tool, and describes quantitative and qualitative features of UBM imaging among pediatric subjects. This summary will include information about the specific applications available to enhance clinical care for pediatric eye disease.

Pediatric Use of Recombinant Human Nerve Growth Factor 20 µg/mL Eye Drops (Cenegermin) for Bilateral Neurotrophic Keratopathy in Congenital Corneal Anesthesia.

PURPOSE: This study aimed to present the efficacy and safety of cenegermin eye drop (Oxervate; Dompè Farmaceutici, Milan, Italy) treatment in a pediatric patient affected by neurotrophic keratopathy (NK) with Goldenhar syndrome. METHODS: This case reports an infant presenting ulceration and a small central opacity in the cornea of the right and left eyes, respectively. The NK bilaterally worsened despite the use of therapeutic contact lenses and temporary partial tarsorrhaphy. Magnetic resonance imaging showed absence and hypoplasia of the right and left trigeminal nerves, respectively. Cenegermin eye drops were administered 1 drop/each eye, 6 times daily for 8 weeks to promote corneal healing. RESULTS: Complete healing was achieved in both eyes after treatment. During the 16-month follow-up period, no epithelial defect, recurrence, or complications were noticed, whereas corneal opacities progressively became clearer, although insignificant improvements in corneal sensitivity or in the reflex tearing were observed. CONCLUSIONS: Cenegermin was effective in treating NK in an infant with Goldenhar syndrome.

Role of Microscope-Intraoperative Optical Coherence Tomography in Pediatric Keratoplasty: AComparative Study.

PURPOSE: We evaluate the role of microscope-integrated intraoperative optical coherence tomography (i-OCT) in pediatric keratoplasty. DESIGN: Combined prospective and retrospective, comparative, interventional study conducted at the Dr Rajendra Prasad Center for Ophthalmic Sciences in New Dehli, India. METHODS: Seventy-five children ≤16 years of age undergoing planned keratoplasty were divided into 2 groups and compared regarding intraoperative course and postoperative outcome. In group 1 (prospective group, n = 56), preoperative anterior segment visualization was performed clinically, with ultrasound biomicroscopy (UBM) and i-OCT and keratoplasty was commenced under i-OCT microscope. In group 2 (retrospective group, n = 19), a conventional microscope was used during keratoplasty. RESULTS: In group 1, i-OCT, UBM, and clinical examination detected retrocorneal membrane in 10%, 7.5%, and 5% (P = .005), iris adhesions in 62.5%, 57.5%, and 20% (P = .02), iris stump in aniridia 15%, 10%, and 0% (P = .001), shallow central anterior chamber in 22.5%, 22.5%, and 7.5% (P = .003), and shallow peripheral anterior chamber in 65%, 60%, and 17.5% (P = .004) of children, respectively. The use of i-OCT affected intraoperative surgeon decision making in 45% and 33% of cases of anterior and posterior lamellar keratoplasty, respectively. During penetrating keratoplasty, concomitant intraoperative procedures were higher in group 1 than in group 2, namely synechiolysis (19/40 vs 2/15; P = .1), pupilloplasty (4/40 vs 0/15; P = .02), lens extraction (4/40 vs 1/15; P = .5), and anterior vitrectomy (2/40 vs 1/15; P = .4). Postoperative secondary interventions were lower (P = .04) in group 1 (48.21% vs 94.74%). CONCLUSIONS: Anterior segment imaging with i-OCT and UBM immediately before surgery improves the surgical planning of children with corneal opacities. In addition, the use of i-OCT refines intraoperative steps, thereby optimizing the postoperative outcome of pediatric keratoplasty.

A mutation in DOP1B identified as a probable cause for autosomal recessive Peters anomaly in a consanguineous family.

Purpose: Peters anomaly (PA) is a heterogeneous developmental disorder characterized by central corneal opacity and iridocorneal or corneolenticular adhesions. Although many causative genes have been identified, most screened patients do not have mutations in the known genes. We aimed to identify the genetic cause of Peters anomaly in a pedigree with three affected individuals. Methods: Slit-lamp biomicroscopy and ultrasound biomicroscopy were performed for definitive diagnosis. Exome sequencing was conducted on the DNA of all three patients. After identification of a candidate causative gene, expression of the gene was assessed with real-time PCR in various ocular tissues of three human embryos and three adults. Results: The patients were affected with isolated PA. The parents of the patients were related to one another. Inheritance of PA was autosomal recessive. After appropriate filtering of the exome data, a homozygous variation in DOP1B remained as the only candidate genetic cause of PA in the pedigree. The variant segregated with disease status in the pedigree and was absent among 800 control Iranians. The variant has been reported in various databases at frequencies of 0.006 or less only in the heterozygous state in some cohorts of African origin. The p.Val1660 amino acid affected by the mutation is completely conserved in mammals and birds during evolution. Expression of DOP1B was shown in all adult and embryonic lens, iris, cornea, sclera, and retina tissues that were tested. Conclusions: DOP1B that encodes DOP1 leucine zipper like protein B was identified as the putative PA-causing gene in pedigree PA-101. As DOP1B is positioned within the Down syndrome chromosomal region on chromosome 21, until now this gene has mostly been studied with respect to brain functions. However, members of the Dopey gene family have been shown to have roles in development in other organisms. Evidence of the expression of DOP1B in various PA-relevant eye tissues, which, to the best of our knowledge, is shown here for the first time, is to be noted. However, this finding does not necessarily implicate a specific role for DOP1B in eye development as the gene is expressed in many tissues. Ultimately, definitive assessment of the contribution of DOP1B to PA pathology awaits identification of mutations in the gene in unrelated patients with PA and functional studies.

A reliable animal model of corneal stromal opacity: Development and validation using in vivo imaging.

PURPOSE: To validate an animal model of corneal stromal opacity by using objective vision-independent in vivo imaging metrics. METHODS: This was a prospective study, with two arms: (i) observational human arm which included 14 patients with healed unilateral ulcerative keratitis; and (ii) experimental rabbit arm, which included 6 New Zealand white rabbits. A 3-mm central wound was created in the left eye of the rabbits by manually removing 200-250 µm of the superficial stroma, followed by rotating-burr application. Both groups underwent photography, high-resolution anterior segment optical coherence tomography, and Scheimpflug imaging using similar diagnostic platforms and standardized image capturing protocols. Parameters studied were relative change in (i) corneal thickness; (ii) corneal epithelial: stromal (E:S) reflectivity ratio; (iii) corneal stromal light scattering using densitometry; and (iv) central corneal keratometry. RESULTS: In the experimental arm, there was a significant decrease in corneal thickness (273 ± 51.3 vs. 407.3 ± 10.3 µm, p = 0.0038), E:S reflectivity ratio (0.71 ± 0.09 vs. 0.99 ± 0.06, p = 0.0018), and keratometry (40.4 ± 2.3 vs. 45.8 ± 0.9D, p = 0.0033) and increase in densitometry (54.2 ± 11.65 vs.18.7 ± 3.8 GSU, p = 0.0001) from baseline, which stabilized at 4 to 8-weeks post-wounding (p > 0.3632). At 8-weeks, the relative change from baseline in corneal thickness (28.4 ± 13.5% vs.22.4 ± 13%, p = 0.368), E:S reflectivity ratio (28.1 ± 11.5% vs. 30.6 ± 8.9%, p = 0.603), corneal densitometry (204.17 ± 97.3% vs. 304.9 ± 113.6%, p = 0.1113), and central corneal keratometry (13.6 ± 6.9% vs. 18.9 ± 7.4%, p = 0.1738) in rabbits was similar to human corneal scars. CONCLUSION: The animal model of corneal opacification was objectively comparable to human post-keratitis scars and can be valuable for in vivo evaluation of emerging therapies for corneal opacities.

Evidence of autophagic vesicles in a patient with Lisch corneal dystrophy / Evidência de vesículas autofágicas em paciente com distrofia corneana de Lisch

ABSTRACT Lisch corneal dystrophy is a rare corneal disease characterized by the distinctive feature of highly vacuolated cells. Although this feature is important, the nature of these vacuoles within corneal cells remains unknown. Here, we sought to analyze corneal cells from a patient diagnosed with Lisch dystrophy to characterize the vacuoles within these cells. Analyses using histopathology examination, confocal microscopy, and transmission electron microscopy were all consistent with previous descriptions of Lisch cells. Importantly, the vacuoles within these cells appeared to be autophagosomes and autolysosomes, and could be stained with an anti-microtubule-associated protein 1A/1B-light chain 3 (LC3) antibody. Taken together, these findings indicate that the vacuoles we observed within superficial corneal cells of a patient with Lisch corneal dystrophy constituted autophagosomes and autolysosomes; this finding has not been previously reported and suggests a need for further analyses to define the role of autophagy in this ocular disease.

RESUMO A distrofia corneana de Lisch é uma doença rara, caracterizada principalmente pela presença de células altamente vacuoladas. Embora esta característica seja importante, a natureza desses vacúolos dentro das células da córnea permanece des conhecida. Aqui, procuramos analisar as células da córnea de um paciente diagnosticado com distrofia de Lisch para caracte rizar os vacúolos dentro dessas células. Análises utilizando exame histopatológico, microscopia confocal e microscopia eletrônica de transmissão foram todas consistentes com descrições previas de células de Lisch. Importante, os vacúolos dentro dessas células pareciam ser autofagossomos e autolisossomos, e po deriam ser corados com um anticorpo proteico 1A/1B-cadeia leve 3 (LC3) da proteína anti-microtúbulo associado a microtúbulos. Em conjunto, esses achados indicam que os vacúolos observados nas células superficiais da córnea de um paciente com distrofia corneana de Lisch constituíram autofagossomos e autolisossomos. Esse achado não foi relatado anteriormente e sugere a necessidade de mais análises para definir o papel da autofagia nessa doença ocular.

Evidence of autophagic vesicles in a patient with Lisch corneal dystrophy.

Lisch corneal dystrophy is a rare corneal disease characterized by the distinctive feature of highly vacuolated cells. Although this feature is important, the nature of these vacuoles within corneal cells remains unknown. Here, we sought to analyze corneal cells from a patient diagnosed with Lisch dystrophy to characterize the vacuoles within these cells. Analyses using histopathology examination, confocal microscopy, and transmission electron microscopy were all consistent with previous descriptions of Lisch cells. Importantly, the vacuoles within these cells appeared to be autophagosomes and autolysosomes, and could be stained with an anti-microtubule-associated protein 1A/1B-light chain 3 (LC3) antibody. Taken together, these findings indicate that the vacuoles we observed within superficial corneal cells of a patient with Lisch corneal dystrophy constituted autophagosomes and autolysosomes; this finding has not been previously reported and suggests a need for further analyses to define the role of autophagy in this ocular disease.

Intraoperative Optical Coherence Tomography to Guide Corneal Biopsy: A Case Report.

PURPOSE: To report on a new application of intraoperative optical coherence tomography (OCT) as a real-time imaging tool to help guide corneal biopsy. METHODS: Single case report. After the negative result of a corneal biopsy, we used intraoperative OCT during repeat biopsy to assist in depth and acquisition of an anterior stromal opacity suspected to be immunoglobulin deposits. RESULTS: The use of intraoperative OCT is a novel tool, which assisted in successful identification and conservative biopsy of corneal immunoglobulin deposits. CONCLUSIONS: Intraoperative OCT is a novel tool that assists in the identification and location of corneal pathology for biopsy.

Quantitative evaluation of corneal epithelial edema after cataract surgery using corneal densitometry: a prospective study.

PURPOSE: The optical density of the cornea can be evaluated quantitatively by "densitometry" using a rotating Scheimpflug camera. Densitometry allows evaluation of corneal opacity in the anterior segment of the eye by quantitative measurement of scattering light. In the present investigation, we evaluate quantitatively minimal subclinical corneal edema after cataract surgery using densitometry. METHODS: Fifty four eyes of 34 patients who underwent cataract surgery were enrolled. Measurement of corneal density was performed using Pentacam® before and on days 1, 3 and 7 after surgery. RESULTS: Densitometry scores increased from 18.12 ± 1.76 before cataract surgery to 21.03 ± 3.84 on day 1 (P < 0.001) and 19.90 ± 2.46 on day 3 (P = 0.018), but recovered to 19.44 ± 1.58 on day 7 (P = 0.131). Total corneal thickness was 549.1 ± 32.7 µm before surgery and increased to 582.7 ± 46.3 µm on day 1 (P = 0.001), but recovered to 566.4 ± 29.7 µm on day 3 (P = 0.097). Densitometry reading correlated positively with corneal thickness (correlation coefficient = 0.13, P = 0.003). CONCLUSIONS: Densitometry is useful to detect corneal edema that is not detectable by slit-lamp examination.

Automated Detection and Classification of Corneal Haze Using Optical Coherence Tomography in Patients With Keratoconus After Cross-Linking.

PURPOSE: To evaluate a proposed technology for offering objective grading and mapping of corneal haze as detected by corneal spectral domain optical coherence tomography after corneal cross-linking. METHODS: This was a retrospective study to evaluate corneal optical coherence tomography images performed on 44 eyes of 44 patients who underwent corneal cross-linking between January 2014 and May 2015, at the American University of Beirut Medical Center. RESULTS: Overall average brightness of the cornea was markedly increased from 43.4% (±6.0) at baseline to 50.2% (±4.4) at 1 month, 47.9% (±4.4) at 3 months, and 46.4% (±5.7) at 6 months with P <0.001, <0.001, and 0.005, respectively. In the anterior stroma, the average brightness significantly increased at 1, 3, and 6 months with values of 54.8% (±3.9), 52.5% (±5.2), and 49.7% (±6.9) with P <0.001, <0.001, and 0.003, respectively. In the mid stroma, the change was clinically significant at 1 and 3 months, whereas in the posterior stroma, it was only significant at 1 month compared with baseline (P = 0.003). Overall, haze was mostly present at 1 month after surgery in all regions, especially in the anterior (32.1%; ±19.2) and mid stromal regions (9.1%; ±18.8), P <0.001 and 0.001, respectively. In contrast, haze in the posterior stromal region peaks at 3 and 6 months after surgery. CONCLUSIONS: Anterior stromal haze was the greatest in intensity and area and it was present for a longer time span than mid and posterior stromal haze. At 12 months, the anterior stroma had still more haze intensity than preoperatively. This image-based software can provide objective and valuable quantitative measurements of corneal haze, which may impact clinical decision-making after different corneal surgeries.

Lipoidal corneal degeneration in aged falcons.

OBJECTIVE: To present a case series of idiopathic lipoidal corneal degeneration in falcons. ANIMALS STUDIED: Five falcons including three peregrine falcons (Falco peregrinus), one prairie falcon (Falco mexicanus), and one red-naped shaheen (Falco peregrinus babylonicus) were observed to develop slowly progressive corneal opacification that began at the temporal limbus and extended centripetally across the cornea over a period of years. Four of the birds were over 20 years old. PROCEDURES: All animals underwent complete ophthalmic examinations. A red-naped shaheen underwent ocular imaging via spectral-domain optical coherence tomography. Two peregrine falcons were euthanized due to declining health, and their eyes were examined histologically. RESULTS: The opacities were pale and granular, with frequent vascularization associated perilimbally. Diffuse neutral lipid was observed in stromal cells throughout the corneal stroma of both clear and opaque areas of the cornea, sparing only the acellular anterior limiting lamina. Clusters of cholesterol crystals surrounded by macrophages were present in the mid-stroma. Fibrosis was evident in a subepithelial location, which separated the epithelium from the anterior limiting lamina. Ultrastructurally, diffuse vacuolization of the keratocytes was observed. No other ophthalmic or systemic abnormalities were noted. CONCLUSIONS: Results suggest that lipid degeneration occurs rarely in captive falcons of advanced age. The underlying cause is unclear. Though unsubstantiated, possible contributing factors include dyslipoproteinemia, corneal trauma, diet, and age-related alterations in corneal metabolism. The initiation of pathology at the temporal limbus, as well as slow progression, suggests that exposure contributes to the onset and progression of this unique keratopathy.

Bilateral anterior segment dysgenesis with the presumed Peters' anomaly in a cat.

A seven-month-old female domestic shorthaired cat was presented for buphthalmos in the right eye and corneal cloudiness in the left eye. Full ophthalmic examinations were performed for both eyes and enucleation was done for the right nonvisual eye. Congenital glaucoma caused by anterior segment dysgenesis was confirmed for the right eye. In the left eye, slit-lamp examination revealed focal corneal edema with several iris strands from iris collarette to the affected posterior corneal surfaces. Circular posterior corneal defect was suggested to be the cause of edema. Goniodysgenesis, additionally, was identified. Taken together, the diagnosis of Peters' anomaly which is a subtype of anterior segment dysgenesis was suggested in the left eye.