Minimum Corneal Diameter and Anterior Steep Axis Curvature Share the Same Meridian: A Novel Finding.

PURPOSE: To define the external scleral sulcus (ESS) on a Scheimpflug image and use it for a morphometric analysis of corneal diameter (CD). DESIGN: Retrospective, cross-sectional study of pediatric Asian-Indian eyes. METHODS: One random eye of 353 subjects between 5 and 18 years underwent 25-scan Pentacam HR imaging. For all scans, densitometry values along the anterior corneal edge were recorded and differentiated. The peaks on the differentiated curve were chosen as the ESS points, and this distance between them was called CD. Vertical (vCD), maximum (maxCD), minimum (minCD) CD and their meridians were defined. Multiple regression models (MRMs) with CD and other Pentacam parameters were built to predict astigmatism and its axis, mean keratometry (Kmean), and Belin/Ambrósio enhanced ectasia display deviation (BAD-D). MRMs were validated using intraclass correlation coefficient (ICC). Estimated horizontal CD (hCD) was validated against digital caliper measurement using ICC. RESULTS: The ICC (95% CI) between caliper and hCD was 0.96 (0.93, 0.97). MRM predictions (P < .001) used CD parameters, anterior chamber depth, corneal volume and distance from the corneal thinnest location to apex. These predictions achieved an ICC of 0.34 (0.18, 0.46), 0.82 (0.78, 0.86), 0.87 (0.84, 0.89), and 0.81 (0.76, 0.84), respectively. The astigmatism axis prediction depended on the minCD and maxCD meridians. Its within-subject SD (4.97°) was less than 2 consecutive Pentacam scan angles (7.2°). CONCLUSIONS: The CD metric strongly correlated with the astigmatism axis, keratometry, and BAD-D. Its spatial description may be significant in corneal treatment planning and disease diagnoses.

New simulation software to predict postoperative corneal stiffness before laser vision correction.

PURPOSE: To develop a new virtual surgery simulation platform to predict postoperative corneal stiffness (Kc mean ) after laser vision correction (LVC) surgery. SETTING: Narayana Nethralaya Eye Hospital and Sankara Nethralaya, India; Humanitas Clinical and Research Center, Italy. DESIGN: Retrospective observational case series. METHODS: 529 eyes from 529 patients from 3 eye centers and 10 post-small-incision lenticule extraction (SMILE) ectasia eyes were included. The software (called AcuSimX) derived the anisotropic, fibril, and extracellular matrix biomechanical properties (using finite element calculation) of the cornea using the preoperative Corvis-ST, Pentacam measurement, and inverse finite element method assuming published healthy collagen fibril orientations. Then, the software-computed postoperative Kc mean was adjusted with an artificial intelligence (AI) model (Orange AI) for measurement uncertainties. A decision tree was developed to classify ectasia from normal eyes using the software-computed and preoperative parameters. RESULTS: In the training cohort (n = 371 eyes from 371 patients), the mean absolute error and intraclass correlation coefficient were 6.24 N/m and 0.84 (95% CI, 0.80-0.87), respectively. Similarly, in the test cohort (n = 158 eyes from 158 patients), these were 6.47 N/m and 0.84 (0.78-0.89), respectively. In the 10 ectasia eyes, the measured in vivo (74.01 [70.01-78.01]) and software-computed (74.1 [69.03-79.17]) Kc mean were not statistically different ( P = .96). Although no statistically significant differences in these values were observed between the stable and ectasia groups ( P ≥ .14), the decision tree classification had an area under the receiver operating characteristic curve of 1.0. CONCLUSIONS: The new software provided an easy-to-use virtual surgery simulation platform for post-LVC corneal stiffness prediction by clinicians and was assessed in post-SMILE ectasia eyes. Further assessments with ectasia after surgeries are required.

Inflammation and dry eye disease-where are we?

The presence of inflammation in dry eye disease (DED) results in increased patient symptomatology, ocular surface damage and worsening tear dysfunction. It also affects the health of meibomian glands and their secretions which further aggravates ocular surface disease. This article reviews current knowledge regarding ocular surface inflammation in DED and explores the relationships between the vicious cycles of DED, inflammation and meibomian gland dysfunction (MGD). The clinical evaluation of eyes with such changes, markers that identify the presence of inflammation on the ocular surface and current treatment options are discussed.

COVID-19 positivity rate in corneal tissue donors - A cause for concern!

Purpose: To determine the postmortem positivity for COVID-19 among voluntary eye donors who had been certified to have died of non-COVID-19 causes. Methods: All donors who donated their corneas (from March 2021 onward) were assessed for COVID-19 positivity tested by nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) test. Relevant screening history was taken prior to collection. Strict precautions were taken during the retrieval as per the guidelines issued by the National Program for Control of Blindness and Visual Impairment and the Eye Bank Association of India, and the tissues were handled as per standard operating protocol. Results: 85 eye calls were attended during this period, of which 56 were home-based and 29 were from a hospital setting. Samples from 12 of the former group of donors were found to be positive for COVID-19 (14%). Conclusion: This study highlights the possibility of postmortem RT-PCR positivity in voluntary corneal tissue donors without a prior history of symptoms, signs, or diagnosis of illness suggestive of COVID-19. It is recommended that postmortem testing of donors should be done by RT-PCR for retrievals made during the pandemic.

Surgical technique for the management of corneal perforation in brittle cornea.

Brittle cornea syndrome is among the few special scenarios in ophthalmology that are a nightmare not only for the operating surgeon but also for the patient. Here, the thin and fragile corneas are unable to maintain the shape and structural integrity of the globe and are more prone to minor traumatic or spontaneous corneal perforations. Suturing a brittle cornea and closure of the corneal perforation in a brittle cornea are very challenging requiring the utmost care and special precautions. If proper measures are not taken during the surgery, it may be difficult to salvage the eye. Hence, it is imperative to diagnose appropriately, suture effectively, taking necessary preventive measures in salvaging these corneas. This manuscript aims at providing tips for handling brittle corneal perforations. It will also discuss the problems encountered during surgery, highlight the suturing techniques that can be customized, and finally give an insight into postoperative care.

Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells.

Corneal haze post refractive surgery is prevented by mitomycin c (MMC) treatment though it can lead to corneal endothelial damage, persistent epithelial defects and necrosis of cells. Suberanilohydroxamic acid (SAHA) however has been proposed to prevent corneal haze without any adverse effects. For clinical application we have investigated the short and long term outcome of cells exposed to SAHA. Human donor cornea, cultured limbal epithelial cells, corneal rims and lenticules were incubated with SAHA and MMC. The cells/tissue was then analyzed by RT-qPCR, immunofluorescence and western blot for markers of apoptosis and fibrosis. The results reveal that short term exposure of SAHA and SAHA + MMC reduced apoptosis levels and increased αSMA expression compared to those treated with MMC. Epithelial cells derived from cultured corneal rim that were incubated with the MMC, SAHA or MMC + SAHA revealed enhanced apoptosis, reduced levels of CK3/CK12, ∆NP63 and COL4A compared to other treatments. In SAHA treated lenticules TGFß induced fibrosis was reduced. The results imply that MMC treatment for corneal haze has both short term and long term adverse effects on cells and the cellular properties. However, a combinatorial treatment of SAHA + MMC prevents expression of corneal fibrotic markers without causing any adverse effect on cellular properties.

Stem cell therapy in coronavirus disease 2019: current evidence and future potential.

The end of 2019 saw the beginning of the coronavirus disease 2019 (COVID-19) pandemic that soared in 2020, affecting 215 countries worldwide, with no signs of abating. In an effort to contain the spread of the disease and treat the infected, researchers are racing against several odds to find an effective solution. The unavailability of timely and affordable or definitive treatment has caused significant morbidity and mortality. Acute respiratory distress syndrome (ARDS) caused by an unregulated host inflammatory response toward the viral infection, followed by multi-organ dysfunction or failure, is one of the primary causes of death in severe cases of COVID-19 infection. Currently, empirical management of respiratory and hematological manifestations along with anti-viral agents is being used to treat the infection. The quest is on for both a vaccine and a more definitive management protocol to curtail the spread. Researchers and clinicians are also exploring the possibility of using cell therapy for severe cases of COVID-19 with ARDS. Mesenchymal stromal cells are known to have immunomodulatory properties and have previously been used to treat viral infections. This review explores the potential of mesenchymal stromal cells as cell therapy for ARDS.

Long-term outcome of custom toric intraocular lens for treating high astigmatism in case of cataract associated with pellucid marginal corneal degeneration.

Pellucid marginal corneal degeneration (PMCD) is a progressive corneal ectasia that ultimately results in high regular astigmatism and correction of this astigmatism is always challenging. However, when a PMCD patient develops a cataract, it provides a golden opportunity to treat this coexisting astigmatism with toric intraocular lens (IOL) implantation. Regular toric IOLs would correct astigmatism only up to 6 diopters in the IOL plane but higher astigmatism would require customization of such IOLs. Our case report describes the long term outcomes of customized toric IOL to tackle this high astigmatism during cataract surgery in PMCD cases.

Resveratrol Rescues Human Corneal Epithelial Cells Cultured in Hyperosmolar Conditions: Potential for Dry Eye Disease Treatment.

PURPOSE: Dry eye disease (DED) is a common ocular surface condition across age groups. Recently, vitamin D deficiency has gained importance as a causative factor, and its supplementation alleviates symptoms of DED. Resveratrol (RES) regulates vitamin D receptors (VDRs) and Notch signaling. We investigated the role of RES on vitamin D levels and Notch signaling under hyperosmolar conditions. METHODS: Human corneal epithelial (HCE-T) cells were treated with RES in hyperosmolar and normal conditions. Quantitative real-time polymerase chain reaction (PCR), immunofluorescence, enzyme-linked immunosorbent assay, and western blot analysis were performed for estimating reactive oxygen species, VDR, secreted 25-hydroxyvitamin D3, and Notch signaling pathway molecules in treated and control cells. RESULTS: HCE-T cells in hyperosmolar conditions had increased reactive oxygen species levels and decreased vitamin D levels that got restored in the presence of RES. Hyperosmolarity also reduced VDR expression and Notch activity that normalized to original levels with RES. In the presence of Notch blocker LY-411575, RES could not restore VDR expression or secreted vitamin D levels in HCE-T cells exposed to hyperosmolar conditions, whereas recombinant Jagged1 restored vitamin D and VDR levels. CONCLUSIONS: RES restores vitamin D levels in hyperosmolar conditions most likely through activation of Notch signaling. Hence, RES can be a potential adjuvant in DED for patients considered for vitamin D treatment.

Unique corneal tomography features of allergic eye disease identified by OCT imaging and artificial intelligence.

The purpose of this study was to assess unique corneal tomographic parameters of allergic eye disease (AED) using optical coherence tomography (OCT) and artificial intelligence (AI). A total of 57 eyes diagnosed with AED were included. The curvature and aberrations of the air-epithelium (A-E) and epithelium-Bowman's layer (E-B) interfaces were calculated. Random forest AI models were built combing this data with the parameters of healthy, forme fruste keratoconus (FFKC) and KC eyes. The AI models were cross-validated with 3-fold random sampling. Each model was limited to 10 trees. The AI model incorporating both A-E and E-B parameters provided the best classification of AED eyes (area under the curve = 0.958, sensitivity = 80.7%, specificity = 98.5%, precision = 88.2%). Further, the E-B interface parameters provided the highest information gain in the AI model. A few AED eyes (n = 9) had tomography parameters similar to FFKC and KC eyes and may be at risk of progression to KC.

Repeatability of OCT Anterior Surface and Bowman's Layer Curvature and Aberrations in Normal and Keratoconic Eyes.

PURPOSE: To study the repeatability of anterior surface and Bowman's layer curvature in normal and keratoconic eyes using optical coherence tomography (OCT). METHODS: In this study, 96 normal and 96 keratoconic eyes underwent corneal imaging using Pentacam (Oculus Optikgeräte, Wetzlar, Germany) and OCT (Triton, Topcon Corporation, Tokyo, Japan). The elevation data from segmented air-epithelium (A-E) and epithelium-Bowman's layer (E-B) interfaces in OCT scans were used to quantify curvature and aberrations. The wavefront aberrations were evaluated with the ray tracing method and 6th order Zernike polynomials. The intraclass correlation coefficient (ICC), within-subject standard deviation (Sw), and coefficient of variation (CoV) were used to assess repeatability. RESULTS: For curvatures, the Sw was less than 0.25 diopters (D) for the normal and keratoconic eyes. The Sw was highest for root mean square of lower order aberrations (0.14 µm) in keratoconic eyes. The CoV for curvatures was well below 0.5% for both groups. For some aberrations irrespective of groups, the CoV was greater because some individual aberrations (mean of three successive measurements) tended to be smaller in magnitude and even a small Sw resulted in a high CoV. For all variables, the ICC ranged between 0.80 and 0.99 for both the OCT and Pentacam measurements. Most variables were similar between the A-E and E-B interfaces (P > .05) for both groups. However, both differed significantly from all Pentacam variables (P < .05) in normal and keratoconic eyes. CONCLUSIONS: The repeatability of OCT curvatures and aberrations compared well with the Pentacam indices for normal and keratoconic eyes. [J Refract Surg. 2020;36(4):247-252.].

Distinct ocular surface soluble factor profile in human corneal dystrophies.

PURPOSE: Corneal dystrophies (CD) are classified as rare eye diseases that results in visual impairment and requires corneal transplant in advanced stages. Ocular surface inflammatory status in different types of CD remains underexplored. Hence, we studied the levels of tear soluble factors in the tears of patients with various types of corneal dystrophies. METHODS: 17 healthy subjects and 30 CD subjects (including epithelial, stromal and endothelial CD) were included in the study. Schirmer's strips were used to collect the tear fluid in all subjects. 27 soluble factors including cytokines, chemokines, soluble cell adhesion molecules and growth factors were measured in the eluted tears by multiplex ELISA or single analyte sandwich ELISA. RESULTS: Percentages of subjects with detectable levels of tear soluble factors were significantly higher in CD compared to controls. Significant higher level of IL-2 was observed in both epithelial and stromal CD. IL-4, TGFß1 and IgE were significantly higher in stromal CD. VCAM, IL-13 and Fractalkine were significantly elevated in epithelial and macular CD. IL-1α, IL-8, IL-12, ANG, Eotaxin, MCP1, RANTES, ICAM1, L-selectin and P-selectin were significantly higher in epithelial CD. TGFBIp was significantly elevated in lattice CD and endothelial CD. CONCLUSION: Distinct set of the tear soluble factors were dysregulated in various types of CD. Increase in tear inflammatory factors was observed in majority of the CD subjects depending on their sub-types. This suggests a plausible role of aberrant inflammation in CD pathobiology. Hence, modulating inflammation could be a potential strategy in improving the prognosis of CD.

Temporal Regulation of Notch Signaling and Its Influence on the Differentiation of Ex Vivo Cultured Limbal Epithelial Cells.

Purpose: Notch signaling plays a vital role in the differentiation and proliferation of corneal epithelial cells from limbal stem cells. The temporal regulation of Notch signaling during this differentiation remains unknown. Hence, we investigated the importance of temporal activation/blockage of Notch signaling during corneal differentiation.Methods: Human limbal epithelial cultures were established with and without Notch activators (rec-Human Jagged1 Fc chimera) and pharmacological blockers (LY-411575). The modulation of Notch signaling was done at different time points during cell differentiation, which were collected on Day 14 for further analysis of differentiation, proliferation, maturation and apoptosis using RT-qPCR and immunofluorescence staining.Results: The activation of Notch signaling at Day 8 resulted in the highest number of mature corneal epithelial cells (p = .008) and pro-apoptosis marker BAX (p = .0001) with no increase in the number of corneal progenitors, and proliferation marker Ki67 compared to untreated controls. Cultures grown in the presence of Notch signaling blockers showed a significantly higher number of corneal progenitors (p = .0001) and proliferation marker Ki67 (p = .02) but lower corneal epithelial marker CK3/CK12 (p = .0007) and no difference in the pro-apoptotic marker BAX compared to untreated controls.Conclusion: During the differentiation of limbal epithelial cells to the corneal epithelial cell type, Day 8 seems to be a crucial window to modulate Notch signaling for a customized outcome.

Corneal Viscous Properties Cannot Be Determined From Air-Puff Applanation.

PURPOSE: To assess whether corneal viscous properties are measureable with air-puff applanation in patients. METHODS: The study had 312 normal eyes, 107 fellow eyes of patients with keratoconus, and 289 keratoconic eyes. The Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) deformation data for all eyes were analyzed using two models. First, a standard linear solid model (SLM) assumed the cornea was an elastic material only. Second, a two-compartment Kelvin-Voigt model (KVM) assumed the cornea was a visco-elastic material. Corneal stiffness and viscosity were calculated. Further, the deflection amplitude was phase shifted virtually relative to the air-puff applanation force to assess whether the KVM was capable of detecting corneal viscous properties from air-puff applanation. This was similar in concept to measured viscoelastic deformations in other soft tissues. The hysteresis area was also calculated with deformation (cornea and whole globe) and deflection (cornea only) amplitude. The greater the magnitude of the hysteresis area, the greater was the magnitude of corneal viscosity (µc). RESULTS: Both the SLM and KVM reported similar magnitudes of corneal stiffnesses (correlation coefficient > 0.99). However, for a given model, corneal stiffness was significantly different between normal, fellow, and keratoconic eyes (P = .001). From the KVM, the corneal viscosity was different between groups (P = .001) but was small in magnitude (order of 10-9). The deflection hysteresis area was also small in magnitude (order of 10-6). In contrast, the KVM detected significant corneal viscosity only when the deflection amplitude was virtually phase shifted with respect to the air-puff applanation force. CONCLUSIONS: No significant corneal viscous response was detected in patients who had air-puff applanation. [J Refract Surg. 2019;35(11):730-736.].

Corneal staining during cataract surgery: Natural course, ASOCT features, and preventive measures.

We report the natural course of the accidental injection of trypan blue into the corneal stroma while performing a routine cataract surgery by a resident during a training session. The corneal staining resolved with conservative medical treatment over 7 weeks. This case describes the anterior segment optical coherence tomography (ASOCT) features of corneal staining. It emphasizes on the relatively benign nature of this dye and the follow-up course. Causes that may be responsible for this untoward complication are highlighted with the necessary preventive measures that need to be taken care are also discussed.

Characterization of Corneal Epithelial Cells in Keratoconus.

PURPOSE: We studied the cellular characteristics of epithelial cells in the cone and extraconal periphery of corneas in keratoconus eyes. METHODS: This prospective observational study was conducted at Narayana Nethralaya Eye Institute. A total of 83 and 42 eyes with keratoconus and normal topography, respectively, were included in the study. Corneal epithelial cells were collected and analyzed for apoptosis, proliferation, epithelial-mesenchymal transition, and differentiation status using molecular and biochemical tools. Statistical analysis was performed using the Student's t-test. RESULTS: Corneal epithelial cells from the cone showed significantly higher expression of proapoptotic marker BAX (P < 0.005) compared to controls. Significantly elevated expression of cell cycle markers CYCLIN D1 (P < 0.005) and Ki67 (P < 0.005) were noted in the extraconal region compared to controls. Cells of the cone showed significantly higher ZO-1 (P < 0.005) and lower vimentin (P < 0.005) compared to controls. Significantly lower expression of the differentiation marker CK3/12 (P < 0.05) was observed in cones compared to controls. CONCLUSIONS: Cones of keratoconic corneas show enhanced cell death, poor differentiation, proliferation and epithelial-mesenchymal transition. The cellular changes of the corneal epithelial cells in the cone and extraconal region differ significantly in a keratoconus corneas. TRANSLATIONAL RELEVANCE: Characterization of patient-specific corneal epithelial cellular status in keratoconus has the potential to determine the optimal treatment and therapeutic outcomes paving the way towards personalized treatment in the future.

Endoilluminator-assisted pediatric cataract surgery with hazy cornea.

The purpose of this study was to demonstrate the usefulness of endoilluminator in pediatric cataract with hazy corneas. We describe a series of three cases of pediatric cataract where visualization of intraocular structures was inadequate under the operating microscope. The endoilluminator was held at the limbus with light directed obliquely to visualize the details of intraocular structures against the hazy cornea using oblique illumination. It allowed structures behind the hazy cornea to be seen with ease. A simple modification in surgical procedure of pediatric cataract using an endoilluminator helps in better visualization of intraocular structures in difficult situations.

Small lens for a big eye: Successful management of anterior megalophthalmos.

We report a case of anterior megalophthalmos and complicated cataract, with apparently smaller lens in both eyes. The right eye had spontaneous retinal detachment. The child underwent cataract surgery in both the eyes with retinal detachment surgery in the right eye. Due to small size of the lenticular bag, a downsized customized intraocular lens (IOL) was implanted. Postoperatively, the IOL was well centered with ambulatory vision till 3 years of follow-up. This case describes this rare disorder and its association with apparently small-sized lens and discusses the course of its management, highlighting the visual rehabilitation with customization of IOLs.