Cornea

: To report two cases of microbial keratitis and/or endophthalmitis involving : Case series. : 24-year-old female with a history of Herpes simplex virus 1 (HSV-1) and keratitis presented with a geographic epithelial defect and infiltrate in the left eye. Cultures were positive for HSV-1 and . Keratitis resolved with topical vancomycin and oral valacyclovir. A 65-year-old female with a history of type II diabetes and failed therapeutic penetrating keratoplasty presented with inferior corneal graft haze and vitreous inflammation of the right eye. Therapeutic penetrating keratoplasty and pars plana vitrectomy were performed, and the corneal button returned positive for . The patient was treated with topical and intravitreal vancomycin as well as topical and systemic steroids. : These cases expand the literature on keratitis and endophthalmitis and corroborate the role of steroid use and prior surgery as paramount risk factors.

Pigment epithelium-derived factor (PEDF) is a widely expressed 50-kDa glycoprotein belonging to the serine protease inhibitor family, with well-established anti-inflammatory functions. Recently, we demonstrated the immunoregulatory role played by PEDF in dry eye disease (DED) by suppressing the maturation of antigen-presenting cells at the ocular surface following exposure to the desiccating stress. In this study, we evaluated the effect of PEDF on the immunosuppressive characteristics of regulatory T cells (Tregs), which are functionally impaired in DED. In the presence of PEDF, the in vitro cultures prevented proinflammatory cytokine (associated with type 17 helper T cells)-induced loss of frequency and suppressive phenotype of Tregs derived from normal mice. Similarly, PEDF maintained the in vitro frequency and enhanced the suppressive phenotype of Tregs derived from DED mice. On systemically treating DED mice with PEDF, moderately higher frequencies and significantly enhanced suppressive function of Tregs were observed in the draining lymphoid tissues, leading to the efficacious amelioration of the disease. Our results demonstrate that PEDF promotes the suppressive capability of Tregs and attenuates their type 17 helper T-cell-mediated dysfunction in DED, thereby playing a role in the suppression of DED.

The assessment of tear fluid components is a common and valuable approach to understanding ocular surface disease and testing the efficacy of novel therapeutic strategies. However, the interpretation and utility of the findings can be limited by changes in the composition of the tear film, particularly in studies requiring repetitive patient sampling. Here, tear samples were collected twice within a one-hour interval to evaluate the short-term reproducibility of an immunoassay aimed to measure the amount of MUC5AC mucin. We found no statistical difference in total protein or MUC5AC content between the two consecutive collections of tear fluid, although the inter-individual variability in each group was high, with coefficients of variation exceeding 30% and 50%, respectively. Scatterplots showed a significant correlation in both protein and MUC5AC following collection within a one-hour interval. These data indicate that, regardless of the high inter-individual variability, repeated collection of tear fluid within an hour interval produces reproducible intra-individual data in terms of MUC5AC mucin content, and suggest that the normal mucin composition of the tear fluid can be re-established within an hour of the initial collection.

PURPOSE: To determine eye drop type and usage frequency and investigate risk factors for no eye drop use in individuals with symptomatic dry eye (DE) in Japan. STUDY DESIGN: Crowdsourced observational study. METHODS: This study was conducted using the DryEyeRhythm smartphone application between November 2016 and September 2019. Data collected included the type and frequency of eye drop use, demographics, medical history, lifestyle, and self-reported symptoms. Symptomatic DE was defined as an Ocular Surface Disease Index total score of ≥ 13. Risk factors for no eye drop use were identified using multivariate logistic regression analyses. RESULTS: Among 2619 individuals with symptomatic DE, 1876 did not use eye drops. The most common eye drop type was artificial tears (53.4%), followed by hyaluronic acid 0.1% (33.1%) and diquafosol sodium 3% (18.7%). Risk factors (odds ratio [95% confidence interval]) for no eye drop use were age (0.97 [0.97-0.98]), body mass index (1.04 [1.01-1.07]), brain disease (0.38 [0.15-0.98]), collagen disease (0.30 [0.13-0.68]), mental illness other than depression and schizophrenia (0.65 [0.45-0.93]), cataract surgery (0.12 [0.02-0.59]), ophthalmic surgery other than cataract and laser-assisted in situ keratomileusis (0.55 [0.34-0.88]), current (0.47 [0.38-0.57]) or past (0.58 [0.43-0.77]) contact lens use, >8 h screen exposure time (1.38 [1.05-1.81]), <6 h (1.24 [1.01-1.52]) and >9 h (1.34 [1.04-1.72]) sleep time, and water intake (0.97 [0.94-0.98]). CONCLUSION: Many participants with symptomatic DE did not use optimized eye drop treatment and identified risk factors for no eye drop use. The DryEyeRhythm application may help improve DE treatment.

PURPOSE: To evaluate the clinical effect of topical cyclosporine A (CsA) (0.05%) on dry eye patients with Sjogren's syndrome (SS) and non-Sjogren's syndrome (NSS). METHOD: This retrospective comparative study includes the dry eye (DE) patients who were treated with topical CsA. DE patients were divided into two groups as follows: DE with Sjogren's syndrome (DE-SS) and DE with Non-Sjogren's syndrome (DE-NSS). Dry eye parameters were recorded at baseline and each visit. RESULTS: Schirmer's test 1 scores were 2.7 ± 0.5 mm at baseline and 3.5 ± 0.7 mm at 12th month in DE-SS, 2.9 ± 0.7 mm at baseline and 9.5 ± 0.7 mm in DE-NSS groups at 12th month. Mean ST score was higher in DE-NSS group than DE-SS group at sixth and 12th months of the treatment (both p = 0.001). Tear break-up time score showed a significant improvement in DE-NSS group, and it was lower in DE-NSS group than DE-SS group group at sixth and 12th months of the treatment (p = 0.044 and 0.027, respectively). Mean OSDI score was lower in DE-NSS group than DE-SS group at sixth and 12th months of the treatment (p = 0.030 and 0.032, respectively). CONCLUSION: Topical CsA seems to be more effective in the treatment of the DE-NSS.

PURPOSE: To describe 3 cases of corneal clearance after the use of topical rho-kinase inhibitor, netarsudil, in the setting of endothelial cell dysfunction in comparison to one case without corneal clearance after the use of netarsudil. METHODS: Four patients presenting to a busy academic clinical corneal practice with visual complaints from corneal edema secondary to endothelial cell dysfunction were treated with topical netarsudil one drop daily in the affected eye. RESULTS: Corneal clearance was observed in 1) a case of peripheral corneal edema in the setting of iridocorneal endothelial syndrome after 4 weeks on netarsudil, 2) a case of corneal edema in the setting of early penetrating keratoplasty graft failure after 2-week use of netarsudil, and 3) a case of corneal edema in the setting of chronic penetrating keratoplasty graft failure after 4-week use of netarsudil. Corneal clearance was not observed in a case of corneal edema in the setting of pseudophakic bullous keratopathy from previous complicated intraocular lens exchange surgery with placement of an anterior chamber intraocular lens after the use of netarsudil for 12 weeks. CONCLUSIONS: Addition of topical rho-kinase inhibitor in the form of netarsudil can result in corneal clearance in a variety of certain cases of endothelial cell dysfunction, not previously documented in the literature.

Fuchs endothelial corneal dystrophy (FECD) is an age-related disease whereby progressive loss of corneal endothelial cells (CEnCs) leads to loss of vision. There is currently a lack of therapeutic interventions as the etiology of the disease is complex, with both genetic and environmental factors. In this study, we have provided further insights into the pathogenesis of the disease, showing a causal relationship between senescence and endothelial-mesenchymal transition (EMT) using in vitro and in vivo models. Ultraviolet A (UVA) light induced EMT and senescence in CEnCs. Senescent cells were arrested in G2/M phase of the cell cycle and responsible for the resulting profibrotic phenotype. Inhibiting ATR signaling and subsequently preventing G2/M arrest attenuated EMT. In vivo, UVA irradiation induced cell cycle re-entry in post mitotic CEnCs, resulting in senescence and fibrosis at 1- and 2-weeks post-UVA. Selectively eliminating senescent cells using the senolytic cocktail of dasatinib and quercetin attenuated UVA-induced fibrosis, highlighting the potential for a new therapeutic intervention for FECD.

PURPOSE: To evaluate corneal subbasal nerve plexus by in vivo confocal microscopy (IVCM) following punctal occlusion in patients with moderate to severe dry eye disease (DED). MATERIALS AND METHODS: Patients with grade 3 or 4 severity of DED based on Delphi Panel dry eye severity grading scheme were enrolled in the study. Permanent inferior punctal occlusion was performed. A comprehensive ophthalmic evaluation, including Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal fluorescein staining, conjunctival Rose bengal staining, Schirmer's test, and corneal sensation by Cochet-Bonnet esthesiometry, were performed at baseline, and 1 and 3 months after punctal occlusion. Furthermore, density and number of corneal subbasal nerves were evaluated by IVCM. RESULTS: Forty-one eyes of 23 patients with a mean age of 46.3 ± 9.0 years were enrolled. Corneal fluorescein staining, Rose bengal staining, and TBUT significantly improved at 3 months following punctal occlusion (p < .015). Corneal esthesiometry significantly increased at both postoperative visits (p < .03), and OSDI scores improved only at 3-month follow-up (p < .005). Nerve density and total number significantly increased 3 months after punctal occlusion (p < .045). Baseline nerve density had significant correlations with TBUT, fluorescein staining, Rose bengal staining (p < .012), but not with esthesiometry, Schirmer scores, or OSDI scores (p > .329). CONCLUSIONS: Corneal subbasal nerve density and total number increased following punctal occlusion in patients with moderate to severe DED. These findings were associated with improvements in corneal sensation, and signs and symptoms of DED. This emphasizes the effect of punctal occlusion in regeneration of corneal subbasal nerve plexus.

PURPOSE: To describe the demographic features and clinical characteristics of patients with herpes keratitis (HK) and limbal stem cell deficiency (LSCD) and identify possible factors associated with development of LSCD after HK. METHODS: In this retrospective case-series study, records of patients with a clinical diagnosis of HK seen at Massachusetts Eye and Ear over a 5-year period were reviewed for evidence of LSCD. Patient demographics, medical history, treatment, and best-corrected visual acuities (BCVAs) were recorded. RESULTS: We identified 626 patients with HK. Fifty-seven had been diagnosed with LSCD (9.3%). Thirteen percent of patients with herpes zoster keratitis (N= 25) and 7% of patients with herpes simplex keratitis (N= 32) had LSCD (P = 0.01). Keratitis caused by herpes zoster virus [odds ratios (OR), 1.77; 95% confidence interval (CI), 0.97-3.19; P = 0.01], stromal involvement (OR, 2.28; 95% CI, 1.27-4.18; P = 0.02), and the use of topical antihypertensives (OR, 2.28; 95% CI, 1.27-4.18; P = 0.02) were found to be associated with a higher likelihood of developing LSCD. The final logarithm of the minimum angle of resolution (LogMAR) BCVA was significantly lower in patients with LSCD compared with those without LSCD with a mean BCVA of 1.34 ± 1.52 LogMar (∼20/200) as compared to 0.18 ± 0.54 LogMar (∼20/30 ± 20/60) in those patients without LSCD (P = 0.005). CONCLUSIONS: Our data suggest that HK may be a risk factor for development of LSCD. Patients with HK should be monitored for the development of LSCD to reduce the risk of chronic ocular surface morbidity.

PURPOSE: To determine the prevalence and risk factors associated with corneal perforation in patients with chronic ocular graft-versus-host disease (oGVHD). METHODS: We reviewed the case records of 405 patients diagnosed with chronic oGVHD over 8 years at a single academic center and assessed the prevalence of corneal perforation in the cohort. We reviewed patient demographics, indication for and type of hematopoietic stem cell transplantation (HSCT), time elapsed between HSCT and perforation, and clinical characteristics including oGVHD severity scores, ocular comorbidities, and topical medications at the time of perforation. Data were analyzed to determine the characteristics of patients with corneal perforation and establish the risk factors. RESULTS: Of the 405 patients with chronic oGVHD, 15 (3.7%) developed a corneal perforation. The mean age of patients at the time of perforation was 64 ± 11 years and 10 (67%) were men. The median time to corneal perforation was 3.3 years post-HSCT. Although perforation occurred unilaterally in all cases, 44% had epithelial defects and 38% had stromal abnormalities in the contralateral eye. Of the patients with corneal perforation, 9 (60%) had a National Institute of Health oGVHD severity score of 2 and 6 (40%) had a score of 3. Patients with chronic oGVHD on antiglaucoma drops had a significantly higher risk of corneal perforation (P < 0.001). CONCLUSIONS: Corneal perforation is a rare but vision-threatening complication of chronic oGVHD. Our study emphasizes the need for frequent and long-term follow-up of patients with oGVHD regardless of the severity of disease. In particular, patients with chronic oGVHD on topical antiglaucoma medications should be monitored closely due to a higher risk for corneal perforation.

The cornea is a transparent avascular tissue on the anterior segment of the eye responsible for providing refractive power and forming a protective barrier against the external environment. Infectious and inflammatory conditions can compromise the structure of the cornea, leading to visual impairment and blindness. Galectins are a group of β-galactoside-binding proteins expressed by immune and non-immune cells that play pivotal roles in innate and adaptive immunity. In this brief review, we discuss how different members of this family of proteins affect both pro-inflammatory and anti-inflammatory responses in the cornea, particularly in the context of infection, transplantation and wound healing. We further describe recent research showing beneficial effects of galectin-targeted therapy in corneal diseases.

AIM: To evaluate and report the outcomes following phacoemulsification on four eyes, 45 years or more after corneal transplantation. METHODS: A retrospective case series of four eyes in three patients (P1, P2, P3), undergoing phacoemulsification at least 45 years after corneal transplantation by Dr Ramon Castroviejo. Corneal graft survival outcome measures included central corneal thickness (CCT), best-corrected visual acuity (BCVA), corneal clarity and endothelial cell count (ECC). RESULTS: Phacoemulsification was successfully completed in all four cases with no instances of graft failure during the postoperative follow-up period, which ranged from 17 months to 76 months. At the conclusion of the follow-up period, all four grafts remained clear, and BCVA remained better than or similar to preoperative values. Long-term follow-up revealed no meaningful changes in CCT after phacoemulsification. All but one case experienced a decrease in ECC, with ECC values in the four cases ranging from 538 cells/mm2 to 1436 cells/mm2 at the conclusion of postoperative follow-up. CONCLUSION: Limited data have been published on the long-term survival of corneal grafts after intraocular surgery, especially for extremely 'mature' corneal transplants. This case series demonstrates that with appropriate preoperative, intraoperative and postoperative measures, successful phacoemulsification can be performed in these cases with excellent long-term results.

With the advancement of computational power, refinement of learning algorithms and architectures, and availability of big data, artificial intelligence (AI) technology, particularly with machine learning and deep learning, is paving the way for 'intelligent' healthcare systems. AI-related research in ophthalmology previously focused on the screening and diagnosis of posterior segment diseases, particularly diabetic retinopathy, age-related macular degeneration and glaucoma. There is now emerging evidence demonstrating the application of AI to the diagnosis and management of a variety of anterior segment conditions. In this review, we provide an overview of AI applications to the anterior segment addressing keratoconus, infectious keratitis, refractive surgery, corneal transplant, adult and paediatric cataracts, angle-closure glaucoma and iris tumour, and highlight important clinical considerations for adoption of AI technologies, potential integration with telemedicine and future directions.