Unilateral Corneal Research Articles

Establishment of a corneal ulcer prognostic model based on machine learning

Corneal infection is a major public health concern worldwide and the most common cause of unilateral corneal blindness. Toxic effects of different microorganisms, such as bacteria and fungi, worsen keratitis leading to corneal perforation even with optimal drug treatment. The cornea forms the main refractive surface of the eye. Diseases affecting the cornea can cause severe visual impairment. Therefore, it is crucial to analyze the risk of corneal perforation and visual impairment in corneal ulcer patients for making early treatment strategies. The modeling of a fully automated prognostic model system was performed in two parts. In the first part, the dataset contained 4973 slit lamp images of corneal ulcer patients in three centers. A deep learning model was developed and tested for segmenting and classifying five lesions (corneal ulcer, corneal scar, hypopyon, corneal descementocele, and corneal neovascularization) in the eyes of corneal ulcer patients. Further, hierarchical quantification was carried out based on policy rules. In the second part, the dataset included clinical data (name, gender, age, best corrected visual acuity, and type of corneal ulcer) of 240 patients with corneal ulcers and respective 1010 slit lamp images under two light sources (natural light and cobalt blue light). The slit lamp images were then quantified hierarchically according to the policy rules developed in the first part of the modeling. Combining the above clinical data, the features were used to build the final prognostic model system for corneal ulcer perforation outcome and visual impairment using machine learning algorithms such as XGBoost, LightGBM. The ROC curve area (AUC value) evaluated the model’s performance. For segmentation of the five lesions, the accuracy rates of hypopyon, descemetocele, corneal ulcer under blue light, and corneal neovascularization were 96.86, 91.64, 90.51, and 93.97, respectively. For the corneal scar lesion classification, the accuracy rate of the final model was 69.76. The XGBoost model performed the best in predicting the 1-month prognosis of patients, with an AUC of 0.81 (95% CI 0.63–1.00) for ulcer perforation and an AUC of 0.77 (95% CI 0.63–0.91) for visual impairment. In predicting the 3-month prognosis of patients, the XGBoost model received the best AUC of 0.97 (95% CI 0.92–1.00) for ulcer perforation, while the LightGBM model achieved the best performance with an AUC of 0.98 (95% CI 0.94–1.00) for visual impairment.

Corneal Opacity in the United States: An American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) Study

This study assesses the case frequencies, underlying causes, and vision outcomes in patients with a diagnosis of corneal opacity in the United States. Retrospective cohort study. Patients in the IRIS® Registry (Intelligent Research in Sight) who received a diagnosis of corneal opacity between January 1, 2013, and November 30,2020. The IRIS Registry contains demographic and clinical data of 79 887 324 patients who sought treatment at eye clinics during the study period. We identified patients with corneal opacity using International Classification of Diseases (ICD), Ninth and Tenth Revisions, codes of 371 (corneal scar) and H17 (corneal opacity), respectively. The analyzed data comprised demographic parameters including age, sex, race, ethnicity, and geographical location. We evaluated clinical data including laterality, cause, disease descriptors, and best-corrected visual acuity (VA) up to 1 year before the onset (± 30 days), at the time of diagnosis, and at 1 year after diagnosis (± 30 days). Case frequencies, causes, and vision outcomes in patients with a diagnosis of corneal opacity. We identified 5 220 382 patients who received a diagnosis of corneal opacity and scars using H17 (ICD, Tenth Revision) and 371.0 (ICD, Ninth Revision) codes over 7 years. The case frequency of corneal opacity during the study period was 6535 cases per 100 000 patients (6.5%). The mean age of the patients was 63.36 ± 18.14 years, and most were female (57.6%). In the cohort, 38.39% and 30.00% of patients had bilateral and unilateral corneal opacity, respectively. Most of the patients affected by corneal opacity were White (69.13%), followed by Black or African American (6.84%). Corneal dystrophies (64.66%) were the most common cause of corneal opacity in the study cohort. Visual acuity of the patients worsened significantly because of corneal opacity (0.46 ± 0.74 logarithm of the minimum angle of resolution [logMAR]) and did not improve to the baseline (0.37 ± 0.68 logMAR) after management (0.43 ± 0.77 logMAR). The multiple linear regression analysis showed worse vision outcomes in female patients (compared with male patients), and Asian, Black or African American, and American Indian or Alaska Native (compared with White) patients. Additionally, worse vision outcomes were observed in patients with opacity associated with corneal malformation, degenerative disorders, edema, injury, and ulcer compared with those with hereditary corneal dystrophy. Our study showed that corneal opacity was diagnosed in 6.5% of patients in the IRIS Registry and primarily associated with corneal dystrophies. The final vision outcomes in patients with corneal opacity were significantly worse compared with baseline. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Can unilateral lattice dystrophy be triggered by cataract surgery in an elderly patient?

ABSTRACT Purpose Aim is to report unilateral lattice corneal dystrophy (LCD) possibly triggered after cataract surgery in an elderly patient and to demonstrate anterior segment optic coherence tomography (AS-OCT) findings. Case Report A 77-year-old male presented with irritation and photophobia in the left eye. His medical history revealed that the patient had undergone cataract surgery on the left eye 5 months ago and his symptoms exaggerated after the surgery. Best corrected visual acuity (BCVA) was 20/32 in OD and 20/63 in OS. Slit lamp examination indicated clear cornea with nuclear sclerosis in the right eye, multiple fine lattice lines at the level of middle stroma in the left eye. The lattice lines extended radially but did not involve the limbus. The overlying epithelium was intact. AS-OCT was consistent with LCD in the left eye with the presence of hyperreflective material at the level of the middle stroma. In contrast, AS-OCT in the right eye showed a normal, healthy cornea. Conclusion LCD is an inherited disease that can rarely present with unilateral involvement. Apart from its unilaterality and lack of limbal-limbal extension, the time of onset of the lattice lines is another distinguishing feature of this case report. Herein, clinical findings appeared at an older age compared to the literature. In addition, the occurrence of findings after phacoemulsification surgery has raised the question that environmental factors may trigger the emergence of unilateral LCD in patients with genetic predisposition. It is not yet known whether unilateral LCD is an asymmetric and asynchronous presentation of bilateral LCD or a different entity triggered by external factors. AS-OCT enables to demonstrate the corneal microstructural changes, and confirm the diagnosis of unilateral LCD by showing that the fellow eye is healthy.

Age-Related Differences in the Mouse Corneal Epithelial Transcriptome and Their Impact on Corneal Wound Healing.

Aging is a risk factor for dry eye. We sought to identify changes in the aged mouse corneal epithelial transcriptome and determine how age affects corneal sensitivity, re-epithelialization, and barrier reformation after corneal debridement. Corneal epithelium of female C57BL/6J (B6) mice of different ages (2, 12, 18, and 24months) was collected, RNA extracted, and bulk RNA sequencing performed. Cornea sensitivity was measured with an esthesiometer in 2- to 3-month-old, 12- to 13-month-old, 18- to 19-month-old, and 22- to 25-month-old female and male mice. The 2-month-old and 18-month-old female and male mice underwent unilateral corneal debridement using a blunt blade. Wound size and fluorescein staining were visualized and photographed at different time points, and a re-epithelialization rate curve was calculated. There were 157 differentially expressed genes in aged mice compared with young mice. Several pathways downregulated with age control cell migration, proteoglycan synthesis, and collagen trimerization, assembly, biosynthesis, and degradation. Male mice had decreased corneal sensitivity compared with female mice at 12 and 24 months of age. Aged mice, irrespective of sex, had delayed corneal re-epithelialization in the first 48 hours and worse corneal fluorescein staining intensity at day 14 than young mice. Aged corneal epithelium has an altered transcriptome. Aged mice regardless of sex heal more slowly and displayed more signs of corneal epithelial defects after wounding than young mice. These results indicate that aging significantly alters the corneal epithelium and its ability to coordinate healing.

Ocular surface complications in children undergoing general anaesthesia: A prospective observational study.

Ophthalmic complications frequently occur after procedures requiring general anaesthesia, but their incidence is widely variable and not well reported in the paediatric population. The aim was to identify the incidence and possible risk factors of postoperative ocular surface complications in a tertiary care centre. This is a prospective study for paediatric patients undergoing general anaesthesia. An ophthalmologist performed the ocular examination after surgery. Parameters assessed were tear breakup time, punctate epithelial erosions and corneal abrasions. Multivariate logistic regression model was used to assess risk factors. A total of 108 paediatric patients were recruited, 36.1% showed abnormal corneal finding: 32 (29.6%) had decreased tear breakup time, three (2.7%) had punctate epithelial erosions, three (2.7%) had both punctate epithelial erosions and decreased tear breakup time and one (0.9%) was found to have a unilateral corneal abrasion postoperatively. A higher rate of corneal complications was noted with younger age, prolonged surgery and surgery in the head and neck region. The rate of postoperative corneal abnormalities in children undergoing general anaesthesia was 36.1%, associated with younger age, prolonged surgery and surgery in the head and neck region.

Recurrent unilateral corneal edema in a 54-year-old patient after endurance sports in low temperature

Introduction: Corneal edema in endurance sports at low temperatures is a rare occurrence, and few reports can be found in the literature. Patient and Clinical Findings: A case of unilateral corneal edema in a 54-year-old man with a history of laser in situ keratomileusis surgery, cataract surgery, and vitrectomy is presented. Recurrent episodes of corneal edema were observed during endurance cycling in temperatures below 10 °C, with complete recovery observed the next day without any treatment. Diagnosis, Interventions, and Outcomes: Pathophysiology and therapeutic strategies were discussed. Local administration of hyperosmolar saline lacked of any effect as did administration of acetazolamide. A protection of the affected eye by contact lens was not successful, but ski goggles could effectively prevent the corneal edema. Conclusions: Some single reports in the literature described roughly similar corneal findings under different conditions. A systematic evaluation of this case could reveal a fateful combination of cold temperature, physical activity, and susceptibility of the corneal endothelium. Protection from cold wind by ski goggles was found to be an effective practical approach.

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

To investigate the correlation between swept-source anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) in congenital corneal opacity (CCO). 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. 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. 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.

Endogenous TSG-6 modulates corneal inflammation following chemical injury

PurposeTumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) is upregulated in various pathophysiological contexts, where it has a diverse repertoire of immunoregulatory functions. Herein, we investigated the expression and function of TSG-6 during corneal homeostasis and after injury. MethodsHuman corneas, eyeballs from BALB/c (TSG-6+/+), TSG-6+/− and TSG-6−/− mice, human immortalized corneal epithelial cells and murine corneal epithelial progenitor cells were prepared for immunostaining and real time PCR analysis of endogenous expression of TSG-6. Mice were subjected to unilateral corneal debridement or alkali burn (AB) injuries and wound healing assessed over time using fluorescein stain, in vivo confocal microscopy and histology. ResultsTSG-6 is endogenously expressed in the human and mouse cornea and established corneal epithelial cell lines and is upregulated after injury. A loss of TSG-6 has no structural and functional effect in the cornea during homeostasis. No differences were noted in the rate of corneal epithelial wound closure between BALB/c, TSG-6+/− and TSG-6−/− mice. TSG-6−/− mice presented decreased inflammatory response within the first 24 h of injury and accelerated corneal wound healing following AB when compared to control mice. ConclusionTSG-6 is endogenously expressed in the cornea and upregulated after injury where it propagates the inflammatory response following chemical injury.

Clinical outcomes of corneal neurotization using sural nerve graft in neurotrophic keratopathy.

To evaluate the efficacy of corneal neurotisation using sural nerve graft coaptation of the contralateral supratrochlear nerve in unilateral neurotrophic keratopathy and corneal anesthesia. Corneal neuralization has emerged as a potential option in the treatment of neurotropic keratopathy, however not free from the predicament. We evaluated the long-term outcome of corneal neurotisation in the treatment of unresponsive unilateral neurotropic keratopathy using surgical variations to mimic and expedient the surgical procedure. A Prospective interventional study involving patients with unilateral neurotrophic keratopathy (NK) who did not respond to medical measures was conducted. The study parameters evaluated were best-corrected visual acuity improvement, ocular surface evaluation parameters [tear break-up time (TBUT), Schirmer's 1, and ocular surface staining scores (corneal and conjunctival staining)], central corneal sensation (Cochet Bonnet esthesiometer), sub-basal nerve fiber length (SBNFL), and sub-basal nerve fiber density (SBNFD) determined by central confocal microscopy at recruitment and during follow-up at 1-month, 3-month, 6-month, 9-month and 12-month respectively, following corneal neurotization. Eleven eyes of 11 patients with unilateral neurotrophic keratopathy (NK) who underwent corneal neurotisation were studied. The mean follow-up was 10.09±2.31months (range, 6-12). Mean best corrected visual acuity in log MAR at baseline, 1.35±0.52 improved significantly to 1.06±0.76 (P = 0.012) at 3 months and continued to 0.55±0.60 (P = 0.027) at 12 months. There was a significant reduction in NK grade severity and improvement in the ocular surface as early as 1 month, and central corneal sensations (P = 0.024) as soon as 3 months. Mean corneal SBNF improved from 3.12±1.84 mm/mm2 to 4.49±1.88 at 1 month (P = 0.008), 13.31±3.61 mm/mm2 (P = 0.028) at 12 months. Mean central corneal SBNFD evident at 6 months was 1.83±2.54no/mm2 (P = 0.018) and 4.90±3.12no/mm2 (P = 0.028) at 12 months. This study substantiates the routine practice of corneal neurotisation by simplifying the intricacies observed during the procedure.

Variable Phenotype of Congenital Corneal Opacities in Biallelic CYP1B1 Pathogenic Variants.

The aim of this study is to describe the variable phenotype of congenital corneal opacities occurring in patients with biallelic CYP1B1 pathogenic variants. A retrospective chart review was conducted to identify patients with congenital corneal opacities and CYP1B1 pathogenic variants seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, anterior segment optical coherence tomography, histopathologic images, and details of genetic testing were reviewed. Three children were identified. All presented with raised intraocular pressure. Two patients showed bilateral limbus-to-limbus avascular corneal opacification that did not resolve with intraocular pressure control; 1 showed unilateral avascular corneal opacity with a crescent of clear cornea, iridocorneal adhesions, iridolenticular adhesions, and classical features of congenital glaucoma in the fellow eye (enlarged corneal diameter, Haab striae, and clearing of the corneal clouding with appropriate intraocular pressure control). The first 2 patients were visually rehabilitated with penetrating keratoplasty. Histopathology revealed distinct features: a variably keratinized epithelium; a thick but discontinuous Bowman-like layer with areas of disruption and abnormal cellularity; Descemet membrane, when observed, showed reduced endothelial cells; and no pathological changes of Haab striae were identified. Two patients had compound heterozygous pathogenic variants in CYP1B1 causing premature stop codons, whereas 1 was homozygous for a pathogenic missense variant. Congenital corneal opacities seen in biallelic CYP1B1 pathogenic variants have a variable phenotype. One is that commonly termed as Peters anomaly type 1 (with iridocorneal adhesions, with or without iridolenticular adhesions) and the other is a limbus-to-limbus opacity, termed CYP1B1 cytopathy. Clinicians should be aware of this phenotypic variability.

Conditional deletion of CD25 in the corneal epithelium reveals sex differences in barrier disruption

PurposeIL-2 promotes activation, clonal expansion, and deletion of T cells. IL-2 signals through its heterotrimeric receptor (IL-2R) consisting of the CD25, CD122 and CD132 chains. CD25 knockout (KO) mice develop Sjögren Syndrome-like disease. This study investigates whether corneal CD25/IL-2 signaling is critical for ocular health. MethodsEyes from C57BL/6 mice were collected and prepared for immunostaining or in-situ hybridization. Bulk RNA sequencing was performed on the corneal epithelium from wild-type and CD25KO mice. We generated a conditional corneal-specific deletion of CD25 in the corneal epithelium (CD25Δ/ΔCEpi). Corneal barrier function was evaluated based on the uptake of a fluorescent dye. Mice were subjected to unilateral corneal debridement, followed by epithelial closure over time. ResultsIn C57BL/6 mice, CD25 mRNA was expressed in ocular tissues. Protein expression of CD25, CD122, and CD132 was confirmed in the corneal epithelium. Delayed corneal re-epithelization was seen in female but not male CD25KO mice. There were 771 differentially expressed genes in the corneal epithelium of CD25KO compared to wild-type mice. While barrier function is disrupted in CD25Δ/ΔCEpi mice, re-epithelialization rates are not delayed. ConclusionsAll three chains of the IL-2R are expressed in the corneal epithelium. Our results indicate for the first time, deleting CD25 systemically in all tissues in the mouse and deleting CD25 locally in just the corneal epithelium compromises corneal epithelial barrier function, leading to dry eye disease in female mice. Future studies are needed to delineate the pathways used by IL-2 signaling to influence cornea homeostasis.

ROLE OF TETRACYCLINE IN CORNEAL NEOVASCULARIZATION

Purpose: To nd the efcacy of topical tetracycline in corneal neovascularization. Material and Methods: In this prospective observational clinical analysis, patients more than fteen year's age of either sex were enrolled. Anterior segment slit lamp examination was performed. Fluorescein 1% dye and rose bengal were used to stain cornea at the bed and margins simultaneously. The area of corneal vascularization was measured in mm using 0.5% uorescein dye. The percentage of neovascularized corneal areas to the entire cornea was calculated. Result: Out of twenty eight patients, twenty one completed follow up period of four months. Among 21 patients, males were 10 (47.6%) and females 11 (52.38%) with unilateral and bilateral corneal neo-vascularization. 15 (71.42%) responded well and showed reduction in corneal new vessels from 7 mm pre-treatment to 2 mm (overall) post treatment at the end of fourth month. Six patient showed poor or no response due to extended brosis. Conclusion: Topical tetracycline has remained quite instrumental in reducing supercial epithelial and sub-epithelial corneal new vessels.

Immunohistochemical Findings in Retrocorneal Membranes of Eyes with Corneal Decompensation after Complicated Intraocular Surgery.

Retrocorneal membranes (RCMs) may result from epithelial ingrowth, stromal keratocytic downgrowth, fibrous metaplasia of the corneal endothelium, or a combination of these processes. In an institutional case series, the clinical history, ocular findings, and immunohistochemical staining results of RCMs were analysed in patients with unilateral corneal decompensation after complicated intraocular surgery. Between January 2021 and September 2022, six retrocorneal membranes were excised during Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) procedures and classified after screening with haematoxylin and eosin, periodic acid-Schiff, elastic van Gieson staining, and immunohistochemical screening with cytokeratin 7 (CK7), anti-cytokeratin (CAM5.2 and AE1/3), cell surface glycoprotein CD34, smooth muscle actin (α-SMA), and vimentin. On the basis of the immunohistochemical screening, the majority of excised RCMs (5 of 6) could histopathologically be classified as membranes originating from fibrous metaplasia of the corneal endothelium. All these RCMs were positive for CK7, α-SMA, and vimentin and negative for CAM5.2 and CD34. In one patient, an RCM had developed after 18 days of corneal contact to a free-floating dexamethasone implant in the anterior chamber and was classified as originating from stromal keratocyte downgrowth (α-SMA- and vimentin-positive, all others negative). All eyes in this series had a previous history of complicated cataract surgery, partially with subsequent intraocular lens exchange. No eyes after previous penetrating keratoplasty were in this series. In this series of eyes with previous complicated intraocular interventions (in most cases cataract surgery and revisions), the dominating RCM belonged to the type originating from fibrous metaplasia of the corneal endothelium.

Successful restoration of corneal surface integrity with a tissue-engineered allogeneic implant in severe keratitis patients

ObjectivesCorneal diseases are among the main causes of blindness, with approximately 4.6 and 23 million patients worldwide suffering from bilateral and unilateral corneal blindness, respectively. The standard treatment for severe corneal diseases is corneal transplantation. However, relevant disadvantages, particularly in high-risk conditions, have focused the attention on the search for alternatives. MethodsWe report interim findings of a phase I-II clinical study evaluating the safety and preliminary efficacy of a tissue-engineered corneal substitute composed of a nanostructured fibrin-agarose biocompatible scaffold combined with allogeneic corneal epithelial and stromal cells (NANOULCOR). 5 subjects (5 eyes) suffering from trophic corneal ulcers refractory to conventional treatments, who combined stromal degradation or fibrosis and limbal stem cell deficiency, were included and treated with this allogeneic anterior corneal substitute. ResultsThe implant completely covered the corneal surface, and ocular surface inflammation decreased following surgery. Only four adverse reactions were registered, and none of them were severe. No detachment, ulcer relapse nor surgical re-interventions were registered after 2 years of follow-up. No signs of graft rejection, local infection or corneal neovascularization were observed either. Efficacy was measured as a significant postoperative improvement in terms of the eye complication grading scales. Anterior segment optical coherence tomography images revealed a more homogeneous and stable ocular surface, with complete scaffold degradation occurring within 3–12 weeks after surgery. ConclusionsOur findings suggest that the surgical application of this allogeneic anterior human corneal substitute is feasible and safe, showing partial efficacy in the restoration of the corneal surface.

Relationship of Density, Depth, and Surface Irregularity of Superficial Corneal Opacification with Visual Acuity

Purpose To explore the relationship between the density, depth, and surface irregularity of superficial corneal opacities and vision. Methods This prospective imaging study included 19 patients with unilateral superficial corneal opacification due to scarring post-microbial keratitis. Each eye underwent an assessment of uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), contact lens corrected visual acuity (CLCVA), and Scheimpflug and anterior segment optical tomography imaging. Regression analysis was performed to detect the association between density, depth of scarring, and the surface irregularity in terms of higher order aberrations (HOA), and keratometry and UCVA, CLCVA, and the difference between BSCVA and CLCVA. Results The mean logMAR UCVA, BSCVA, and CLCVA were 0.76, 0.35, and 0.28, respectively. The corneal scars had a mean thickness of 158.7 ± 61 µ and density of 65.73 ± 24.46 GSU. Bivariate analysis model for UCVA showed an association with Z4 2 secondary astigmatism (p = 0.02), Z4 4 quadrafoil (p = 0.01), combined coma Z3 ± 1(p = 0.03), and combined HOA Z3–Z6 (p = 0.045), out of which Z4 4 Quadrafoil (p = 0.04) was most significant with multivariate analysis. Bivariate analysis for BCVA-CLVA showed association with Z3 1 coma horizontal (p = 0.04), Z3 3 oblique trefoil (p = 0.02), Z4 0 primary spherical aberration (p = 0.008), and Z5 − 5 (p = 0.007), out of which Z3 1 horizontal coma (p = 0.04) and Z4 0 spherical aberration (p = 0.009) were significant on multivariate analysis. Change in densitometry, corneal thickness, epithelial:stromal reflectivity ratio, scar depth, and keratometry did not show any significant association with UCVA, BSCVA-CLCVA, or CLCVA. Conclusion In superficial corneal stromal scarring, deranged surface irregularity parameters like higher-order aberrations affect the final visual acuity more than the depth or density of the opacity.

Corneal nerve regeneration is affected by scar location in herpes simplex keratitis: A longitudinal in vivo confocal microscopy study

PurposeTo assess the effect of corneal scar location on corneal nerve regeneration in patients with herpes simplex virus (HSV) keratitis in their affected and contralateral eyes over a 1-year period by in vivo confocal microscopy (IVCM), and to correlate these findings to corneal sensation measured by Cochet-Bonnet Esthesiometer. MethodsProspective, longitudinal, case-control study. Bilateral corneal nerve density and corneal sensation were analyzed centrally and peripherally in 24 healthy controls and 23 patients with unilateral HSV-related corneal scars using IVCM. ResultsIn the central scar (CS) group, total nerve density in the central cornea remained significantly lower compared to controls at follow-up (11.05 ± 1.97mm/mm2, p < 0.001), and no significant nerve regeneration was observed (p = 0.090). At follow-up, total nerve density was not significantly different from controls in the central and peripheral cornea of the peripheral scar (PS) group (all p > 0.05), but significant nerve regeneration was observed in central corneas (16.39 ± 2.39mm/mm2, p = 0.007) compared to baseline. In contralateral eyes, no significant corneal nerve regeneration was observed in central or peripheral corneas of patients with central scars or peripheral scars at 1-year follow-up, compared to baseline (p > 0.05). There was a positive correlation between corneal nerve density and sensation in both central (R = 0.53, p < 0.0001) and peripheral corneas (R = 0.27, p = 0.0004). In the CS group, the corneal sensitivity was <4 cm in 4 (30.8%) and 7 (53.8%) patients in the central and peripheral corneas at baseline, and in 5 (38.5%) and 2 subjects (15.4%) at follow-up, whereas in the PS group only 1 patient (10%) showed a corneal sensation < 4 cm in the central cornea at baseline, and only 1 (10.0%), 3 (30.0%) and 1 (10.0%) patients at follow-up in the central, affected and opposite area of the cornea, respectively. ConclusionThe location of HSV scarring in the cornea affects the level of corneal nerve regeneration. Eyes with central corneal scar have a diminished capacity to regenerate nerves in central cornea, show a more severe reduction in corneal sensation in the central and peripheral corneas that persist at follow-up, and have a reduced capability to restore the corneal sensitivity above the cut-off of 4 cm. Thus, clinicians should be aware that CS patients would benefit from closer monitoring for potential complications associated with neurotrophic keratopathy, as they have a lower likelihood for nerve regeneration.

Unilateral corneal insult also alters sensory nerve activity in the contralateral eye

AbstractWhen the ocular surface of one eye is inflamed or injured, its corneal sensory nerve activity is modified, which in turn evokes ocular discomfort, irritation, and pain sensations referred to the affected eye. Some patients with unilateral ocular inflammation, infection, or surgery also report discomfort and pain in the contralateral eye. Are these sensations experienced at the fellow eye due to alterations of its sensory nerve activity?To test this hypothesis, we recorded in vitro the activity of corneal mechanonociceptor, polymodal nociceptor and cold thermoreceptor nerves of both eyes of guinea pigs previously subjected unilaterally to three different experimental inflammatory and lesion conditions: UV‐induced photokeratitis, microkeratome corneal surgery, and chronic tear deficiency caused by removal of the main lacrimal gland. Recordings from the eyes of naïve animals were used as control.Compared with the naïve guinea pigs, animals subjected to unilateral UV‐induced mild corneal inflammation, showed inhibition of the spontaneous and stimulus‐evoked activity of cold thermoreceptors, and increased activity (sensitization) of nociceptors affecting both the ipsilateral and the contralateral eye. Unilateral microkeratome surgery affected the activity of nociceptors mostly, inducing sensitization in both eyes. Chronic eye dryness by removal of the main lacrimal gland increased cold thermoreceptor activity in both eyes. These results show that after unilateral eye damage, corneal sensory nerve activity is altered in both eyes, although to a lesser degree in the contralateral eye.This is the first direct demonstration that unilateral corneal nerve insult, and especially ocular surface inflammation, functionally affects the activity of the different types of corneal sensory nerves in both the ipsilateral and contralateral eyes. The mechanisms underlying the changes of contralateral sensory nerve activity remain to be determined, although available data support the involvement of the immune system. The present results have two main implications: (a) contralateral eyes cannot be considered as a control in experimental designs of both preclinical and clinical studies; and, (b) clinicians must consider the convenience of treating both eyes of patients with unilateral ocular conditions to avoid pain and secondary undesirable effects in the fellow eye.

Post-Market Evaluation of Rotational Stability and Visual Performance of a New Toric Intraocular Lens with Frosted Haptics.

To evaluate 3-month rotational stability, and visual and refractive outcomes of a toric intraocular lens (IOL) with frosted haptics. A post-market, prospective, multi-center, single-arm, open-label study conducted at seven clinical sites in the United States. Two hundred and two eyes of 133 subjects with unilateral or bilateral cataracts and corneal astigmatism were implanted with the Tecnis Toric II IOL, Models ZCU150 to 600 (Johnson & Johnson Surgical Vision, Inc.). Lens axis misalignment/rotation, visual acuity, manifest refraction, and surgeon and patient satisfaction were evaluated 3 months postoperatively. Lens rotation was determined with operative and postoperative visit photographs and was analyzed by two independent masked analysts. Mean absolute lens rotation was 0.82° ± 1.00° and 0.94° ± 0.71° at 1 day (n = 189 eyes) and 3 months (n = 185 eyes), respectively. Absolute lens rotation was ≤5° in 98.9% and 100% of eyes at 1 day and 3 months, respectively. At 3 months, postoperative monocular uncorrected and corrected distance visual acuities were 0.004 ± 0.115 LogMAR (20/20) and -0.066 ± 0.092 LogMAR (20/17), mean spherical equivalent was -0.25 D ± 0.35 D and residual refractive cylinder was +0.27 D ± 0.33 D. Surgeons were satisfied/very satisfied with overall clinical outcomes and rotational stability in 99% of eyes, and with uncorrected distance vision in 98.5% of eyes. The study results demonstrate that the Tecnis Toric II IOL has excellent rotational stability with a high percentage of study eyes being within 5° of intended orientation. The study lens demonstrated excellent uncorrected distance visual acuity, reduction of cylinder, and exceptional patient and surgeon satisfaction.

Contralateral inflammatory effects on the trigeminal ganglion after unilateral corneal lesion

AbstractThe purpose of this study was to test whether a corneal injury can stimulate inflammation in the trigeminal ganglion (TG) located (i) on the same side, or (ii) on the opposite site of a cornea alkali burn.Following monolateral administration of a corneal alkali burn, we performed in vivo magnetic resonance imaging (MRI) of the brain before and after ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) contrast to track macrophages. Trigeminal ganglia were stained for Prussian Blue and inflammatory cell markers. Moreover, the tissue levels of pro‐inflammatory cytokines Interleukin‐1β, TNF‐α, and VEGF were quantified on days 1, 4, and 8, and 4 days after corneal topical anti‐inflammatory treatment with 0.2% dexamethasone. The expression of Substance P and its receptor NK‐1R was measured in the TG on day 4.Corneal alkali burn induced leukocyte infiltration, including T cells, in the right TG at 4 and 8 days. In vivo MRI showed an increased contrast uptake in the right TG, which peaked at day 8. Prussian Blue(+) USPIO(+) macrophages were observed in the right TG and exhibited an M2 phenotype. The M2‐macrophage infiltration was preponderant in the TG after damage. The proinflammatory cytokines Substance P and NK‐1R were significantly increased in both the TGs. The expression of IL‐1β and VEGF‐A was significantly reduced in the right TG with dexamethasone treatment.Our data support: (i) bilateral onset of inflammation in the TG following ocular surface damage; (ii) involvement of the neuropeptide Substance P in the propagation of inflammation from the cornea to the TG through corneal nerves.

Bilateral changes in corneal sensitivity after unilateral corneal infections

AbstractOcular infections such as herpes simplex virus (HSV) keratitis result in ocular sensitivity changes. During acute HSV episodes and eventually during postherpetic outbreaks, spontaneous pain and hyperalgesia are experienced, being reduced by treatment with Na+ channel blockers (not only by local anaesthetics but also by gabapentin, lacosamide or amitriptyline). At the same time, patients commonly develop hypoesthesia due to the decrease of sensitivity to mechanical stimulation, whose appearance could be due to the internalization of Na+ channels in trigeminal sensory neurons innervating the infected cornea.When explored using a gas esthesiometer that allows selective mechanical, chemical, heat and cold stimulation, HSV‐infected corneas showed those sensitivity disturbances to be expected when corneal polymodal nociceptor activity is altered. On the contrary, sensitivity to cold stimuli is not modified, which suggest that cold thermosensitive ocular neurons are not infected by the virus. A surprising result is the alteration, in the same sense although to a lesser degree, of the sensitivity of the contralateral eye. This contralateral altered sensitivity could be caused by a subclinical HSV infection of the contralateral side. Another possibility is that to be due to a neuroimmune interaction that ends up affecting the activity of sensory nerves of both eyes, in a similar way to what happens in non‐infectious inflammatory processes affecting only one eye.(PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103)