UVB induced reactivation leads to HSV1 in the corneas of virtually all latently infected mice and requires STING to develop corneal disease.

Reactivation of latent herpes simplex type 1 results in virus returning to the cornea leading to recurrent herpetic stromal keratitis (rHSK). We compare two competing models to reactivate viruses from latency, UV-B irradiation and cyclophosphamide (CP). Results revealed that while both result in corneal recrudescence, only UV-B irradiation results in rHSK. To better understand the dynamics of reactivation, we analyzed corneas for both the presence of infectious viruses and the dynamics of exposure to multiple reactivations using UV-B. We noted that multiple reactivations result in progressively worse corneal disease. We also noted that expression of IFNα and STING, surragate markers for the presence of virus, are induced by the presence of reactivated virus. Studies to determine the importance of STING to the development of HSK revealed that in the absence of STING, mice do not develop significant HSK and the magnitude of the infiltrate of CD45+ cells in these corneas is significantly reduced. The resulting paucity of CD45+CD11b+GR-1+F4/80-neutrophils, and to a lesser extent CD45+CD11b+GR-1-F4/80+ macrophages in B6-STING KO mice following reactivation is likely the underlying cause for lack of rHSK as has been noted by ourselves and others. These results underscore the critical importance of STING's role in developing rHSK.

Corneal Epithelial Changes in Diabetic Patients: A Review.

The relationship between diabetes mellitus and ocular complications has been extensively studied by many authors. Diabetic keratopathy has already been well characterized and defined as a clinical entity. This review focuses on exploring corneal epithelial changes in diabetic patients, aiming to provide a pragmatic overview of the existing knowledge on this topic. The paper systematically examines alterations in corneal epithelial structure and their impact on diabetic patients. Advanced imaging techniques are also discussed for their role in precise characterization and improved diagnostics. Additionally, the paper explores the mechanisms behind corneal epithelial changes in diabetes, looking at factors such as hyperglycemia, oxidative stress, and Advanced Glycation End-Products. The impact of altered corneal epithelial integrity on barrier function and susceptibility to external issues is considered, addressing potential links to heightened proteolytic enzyme activities and delayed wound healing observed in diabetic individuals. The review also covers the practical implications of corneal epithelial changes, including the association with corneal erosions, persistent epithelial defects, and an increased risk of dry eye syndrome in diabetic patients.

Severity Classification of Limbal Stem Cell Failure Due to Steven Johnson Syndrome in the Light of the Classification Consensus of Limbal Stem Cell Deficiency.

OBJECTIVES: To examine and to understand the limbal stem-cell deficiency (LSCD) because of Steven-Johnson syndrome (SJS) in line with the new classification system for the first time in the literature. METHODS: Medical records of patients with LSCD because of SJS were reviewed retrospectively. In addition to demographic data and ophthalmologic or systemic findings, anterior segment photographs of the patients were reviewed retrospectively. Limbal stem-cell deficiency severity was graded according to the classification published by the Limbal Stem Cell Working Group. RESULTS: Twenty-four eyes of 14 patients with eye involvement secondary to SJS were included in the study. The mean age of the patients was 36.09±16.70 (9-58) years and the female-to-male ratio was 11:3. The anterior segment photographs of the patients were evaluated by two independent masked observers. Limbal stem-cell deficiency severity was graded according to the classification published by Deng et al. Corneal opacity was divided into three stages according to the area of involvement. Corneal opacity was classified as Stage I if the central 5 mm region of the cornea was not affected, as Stage II if the central 5 mm region of the cornea was affected, and as Stage III if the entire corneal surface was affected. Limbal involvement was classified as Stage A if it was below 50%, as Stage B if it was between 50% and 100%, and as Stage C if it was 100%. CONCLUSION: This is the first study in the literature to describe and classify LSCD because of SJS, according to the new LSCD classification. Consistent with the results, LSCD follows a bimodal distribution. Most patients demonstrated severe (Stage III-32.14%) or mild (Stage IA-21.42%) LSCD.

Effects of hypoxia in the diabetic corneal stroma microenvironment.

Corneal dysfunctions associated with Diabetes Mellitus (DM), termed diabetic keratopathy (DK), can cause impaired vision and/or blindness. Hypoxia affects both Type 1 (T1DM) and Type 2 (T2DM) surprisingly, the role of hypoxia in DK is unexplored. The aim of this study was to examine the impact of hypoxia in vitro on primary human corneal stromal cells derived from Healthy (HCFs), and diabetic (T1DMs and T2DMs) subjects, by exposing them to normoxic (21% O2) or hypoxic (2% O2) conditions through 2D and 3D in vitro models. Our data revealed that hypoxia affected T2DMs by slowing their wound healing capacity, leading to significant alterations in oxidative stress-related markers, mitochondrial health, cellular homeostasis, and endoplasmic reticulum health (ER) along with fibrotic development. In T1DMs, hypoxia significantly modulated markers related to membrane permeabilization, oxidative stress via apoptotic marker (BAX), and protein degradation. Hypoxic environment induced oxidative stress (NOQ1 mediated reduction of superoxide in T1DMs and Nrf2 mediated oxidative stress in T2DMs), modulation in mitochondrial health (Heat shock protein 27 (HSP27), and dysregulation of cellular homeostasis (HSP90) in both T1DMs and T2DMs. This data underscores the significant impact of hypoxia on the diabetic cornea. Further studies are warranted to delineate the complex interactions.

Late-Onset Traumatic Corneal Conjunctival Epithelial Disorders due to Granular Formation After Cosmetic Suture Blepharoplasty.

PURPOSE: The purpose of this study was to report conjunctival granular formation as one of the causative factors of a traumatic corneal conjunctival epithelial disorder after plastic suture blepharoplasty. METHODS: Clinical charts of 7 patients who had visited Ohshima Eye Hospital with a symptomatic corneal epithelial disorder and history of suture blepharoplasty were reviewed. Clinical evidence of conjunctival granular formations was observed in all patients at the tarsal conjunctiva facing to corneal conjunctival traumatic epithelial disorders. The desired outcome was to alleviate the disorder. The assessment included tabulating results after the placement of a soft contact lens bandage and subsequent partial tarsal plate resection of the granular formation. RESULT: Seven women (mean age 45.0 ± 10.9 years) enrolled in this study had previously undergone suture blepharoplasty (mean 18.3 ± 6.9 years before). Soft contact lens bandages relieved all of the patients' complaints immediately. After resecting the granular formation, the traumatic corneal conjunctival epithelial disorder disappeared, and no recurrence was observed after surgery. CONCLUSIONS: The conjunctival granular formation within the tarsal conjunctiva after suture blepharoplasty caused the late-onset traumatic corneal conjunctival epithelial disorder. A complete cure was obtained after resection of the granular formation at the tarsal conjunctiva. To the best of our knowledge, this is the first report to identify the removal of granular formations in 7 patients with late-onset traumatic corneal conjunctival disorders many years after blepharoplasty. The resection of these lesions is a promising procedure to treat late-onset ocular epithelial disorder after suture blepharoplasty.

Glaucoma after penetrating keratoplasty and keratoprosthesis.

PURPOSE: To compare visual and glaucoma outcomes in patients with known glaucoma after a penetrating keratoplasty (PKP) or a Boston Keratoprosthesis Type 1 (KPro) as a second corneal replacement procedure. DESIGN: Retrospective interventional case series. PARTICIPANTS: Charts of 141 eyes that underwent either a PKP or KPro at the Centre hospitalier de l'Université de Montréal after one failed PKP from 2008 to 2020 were reviewed. Forty-six eyes with preoperative glaucoma were included. METHODS: Data collected included demographics, indication for the initial surgery, best corrected visual acuity (BCVA), concurrent ocular disorders, number of glaucoma medications, need for glaucoma surgery, cup-to-disc ratios (CDRs), mean RNFL thickness, and visual field (VF) characteristics. Primary outcomes were glaucoma progression trends. Secondary outcomes were visual outcomes and need for additional procedures. RESULTS: Mean follow-up was 4.7 years for the PKP and 7.3 for the KPro group (P<0.007). 30.6% of PKP compared to 70.5% of KPro patients were diagnosed with glaucoma preoperatively. Glaucoma worsened similarly in both groups; this is based on an analysis of the number of glaucoma medications, CDR, need for glaucoma surgery, and characteristic VF changes. Patients in the PKP group required significantly more regrafts than patients in the KPro group (31.8 vs. 8.3%; P=0.045). CONCLUSIONS: A preoperative diagnosis of glaucoma does not preclude KPro implantation. In glaucomatous eyes, the disease progressed similarly in both groups. Since both procedures increase the risk of worsening glaucoma, close follow-up is recommended. KPro may decrease the need for further corneal transplantation surgery.

Patch endothelial keratoplasty for corneal perforations secondary to ocular surface disease: case series.

BACKGROUND: Corneal perforation is an ophthalmic emergency. The conventional management of corneal perforation can be associated with severe complications especially in patients with ocular surface disease. Endothelial keratoplasty has been suggested as an alternative surgical technique for the management of corneal perforations. We present a case series of nine patients with corneal perforation and ocular surface disease managed with secondary patch endothelial keratoplasty. METHODS: This is a retrospective case series of nine patch endothelial keratoplasties performed between 2016 and 2022 at a quaternary eye hospital in Australia. The surgical technique is similar to conventional endothelial keratoplasty except descemetorhexis was not performed. RESULTS: A total of 9 cases were treated during the review period. Eight of the nine cases had an improvement in visual acuity. One case failed to achieve corneal tectonic objective. CONCLUSION: Patch endothelial keratoplasty is a safe secondary procedure for the management of corneal perforations in patients with ocular surface disease.

Is Astigmatism Correction Necessary for Patients With Cataract Who Have Corneal Astigmatism of Less Than 0.75 D?

PURPOSE: To investigate the proportion of patients with predicted refractive astigmatism (PRA) of 0.75 diopters (D) or greater and associated risk factors among cataract surgery candidates with low corneal astigmatism. METHODS: A retrospective cross-sectional study was conducted in Zhongshan Ophthalmic Center, Guangzhou, China. Patients with cataract who had preoperative simulated keratometric astigmatism of less than 0.75 D were recruited. The PRA was calculated by Barrett toric calculator using posterior corneal astigmatism (PCA) measured by the IOLMaster 700 (Carl Zeiss Meditec AG) and corneal surgically induced astigmatism (SIA). Two corneal incision locations (temporal [0°/180°], 135° incision) and varying magnitudes (0.10 to 0.60 D) were considered for SIA. Multiple logistic regression analysis was used to explore risk factors associated with PRA of 0.75 D or greater and build predictive model. Sensitivity analysis was performed using PRA threshold of 0.50 D. RESULTS: A total of 1,750 eyes from 1,750 patients were included (mean age: 60.14 ± 13.24 years, 42.91% male, 1,010 right eyes and 740 left eyes). The 135° incision (odds ratio [OR]: 17.86) and against-the-rule (ATR) astigmatism (OR: 37.55) are the major risk factors for PRA of 0.75 D or greater. Higher simulated keratometric astigmatism (OR: 2.03), larger PCA (OR: 1.64), and surgically induced astigmatism (OR: 1.29) also significantly increased the risk of PRA of 0.75 D or greater. Nomogram model were constructed with an area under curve of 0.90. CONCLUSIONS: For patients with corneal astigmatism of less than 0.75 D, temporal incision and measured PCA is preferred. Those patients with ATR astigmatism should be considered for astigmatism correction when using a 135° incision. [J Refract Surg. 2023;39(12):850-855.].

Late-Onset Chronic Corneal Fistula Following Phototherapeutic Keratectomy: A Case Report and Importance of Early Detection.

BACKGROUND We report a case of late-onset chronic fistula in a decompensated cornea after multiple ocular surgeries and a recent phototherapeutic keratectomy (PTK). CASE REPORT A 73-year-old woman presented to our service with a past ocular history of bilateral chronic angle closure glaucoma and pseudophakic bullous keratopathy in the left eye. Given a history of long-term uncontrolled glaucoma with advanced disc cupping and poor visual potential, the patient underwent multiple palliative procedures, including, most recently, a PTK. Few years later she presented with a spontaneous late onset of slowly appearing corneal leak on fluorescein staining upon routine clinical examination. Corrected distance visual acuity was hand motion and intraocular pressure (IOP) was 40 mmHg in the affected eye. Serial anterior segment optical coherence tomography (AS-OCT) sections were obtained, which aided in understanding the current presentation and revealed distinctive multilayer corneal changes during the healing process. The patient was successfully managed with cyanoacrylate corneal gluing and ocular hypotensive medications, which halted the corneal leak. CONCLUSIONS We report a case of a rare finding of corneal fistula in an eye with multiple previous ocular surgeries, and provide an explanation of the possible etiopathogenesis. We also highlight the pivotal role of AS-OCT for evaluating such cases and stress the importance of early detection of similar subtle leaks in the setting of a formed anterior chamber, which can often be missed, carrying a risk of infection.

Self-limited corneal ectasia in a post-LASIK eye after cataract surgery: A case report.

INTRODUCTION: To present a case with a history of laser in situ keratomileusis (LASIK) developing central conic protrusion after phacoemulsification cataract surgery, which spontaneously resolved 5 months postoperatively. PATIENT CONCERNS: A 55-year-old female who underwent myopic LASIK surgery 10 years ago presented to the clinic with bilateral cataracts and without ectasia. Following phacoemulsification cataract surgery and intraocular lens implantation in the right eye, the patient experienced a significant increase in spherical equivalent and corneal astigmatism. DIAGNOSES: Based on a central conic protrusion on topography examination, surgically-induced corneal ectasia was diagnosed. INTERVENTIONS: Topical lubricants, corticosteroids, and serial follow-up with corneal topography. OUTCOMES: The corneal protrusion gradually resolved over a period of 5 months. LESSONS: For post-LASIK patient who developed corneal protrusion following uneventful cataract surgery with a clear corneal incision, the clear corneal wound may have disrupted the biomechanical stability of the post-LASIK eye, compromising the peripheral stromal integrity. Additionally, postoperative inflammation could have contributed to corneal ectasia. Smaller clear corneal wounds or scleral tunnel entry during cataract surgery in post-LASIK eyes should be considered. Monitoring wound healing and using topical steroids can aid in achieving satisfactory outcomes and reducing the potential vision-threatening complications associated with corneal ectasia.

Case Report: Role of Anterior Segment Optical Coherence Tomography for Managing Failed Endothelial Keratoplasty Graft.

SIGNIFICANCE: Some patients show poor visual outcomes after Descemet stripping automated endothelial keratoplasty. In such cases, secondary Descemet membrane endothelial keratoplasty can be performed to achieve complete visual recovery. Anterior segment optical coherence tomography (AS-OCT) is a valuable tool for the follow-up of posterior lamellar keratoplasty outcomes and complications. PURPOSE: This study aimed to report the clinical outcome of secondary Descemet membrane endothelial keratoplasty for managing poor visual results in a patient with graft failure after a previous Descemet stripping automated endothelial keratoplasty, highlighting the importance of AS-OCT in the follow-up of endothelial keratoplasty. CASE REPORT: A 38-year-old woman with high myopia underwent Descemet stripping automated endothelial keratoplasty for bullous keratopathy after explantation of an angle-supported phakic intraocular lens. Two years after keratoplasty, the patient experienced poor visual acuity (counting fingers), and significant corneal edema was observed on clinical examination hindering visualization of the anterior chamber structures. Anterior segment optical coherence tomography showed a failed and thickened graft adhering well to the recipient cornea in an anterior chamber without other comorbidities. Therefore, the graft was removed and replaced with a Descemet membrane endothelial keratoplasty graft without any complications. One year later, the clinical outcome was evaluated by comparing the pre-operative and post-operative best-corrected visual acuity, biomicroscopy findings, endothelial cell density, and corneal central thickness. CONCLUSIONS: Anterior segment optical coherence tomography is an important tool when deciding on the surgical technique to be applied and for the post-surgical monitoring of endothelial corneal grafts. This case demonstrates the successful management of Descemet stripping automated endothelial keratoplasty graft failure with Descemet membrane endothelial keratoplasty graft, highlighting the importance of AS-OCT in detecting complications such as graft dislocation and primary graft failure. In addition, corneal thickness measured using AS-OCT serves as a critical predictor of graft failure, as observed in this case.

[Surgical technique of keratoplasty with simultaneous implantation of a continuous ring or ring segment into the graft]. / Khirurgicheskaya tekhnika keratoplastiki s odnomomentnoi implantatsiei tsel'nogo ili razomknutogo kol'tsa v transplantat.

The article presents the surgical technique of penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) with femtosecond-laser assistance involving simultaneous implantation of an intracorneal continuous ring (ICCR) or an intracorneal ring segment (ICRS) into the graft. Surgical technique no. 1 - keratoplasty with simultaneous implantation of ICRS. Intrastromal circular tunnel is formed in the central zone of donor cornea using femtosecond laser. Then penetrating trepanation 8.1 mm in diameter is performed symmetrically to the formed tunnel. After preparing penetrating or lamellar recipient bed, suture fixation is placed in the corneal transplant, then the ICRS is implanted into the graft. Surgical technique no. 2 - keratoplasty with simultaneous implantation of ICCR. The donor cornea is dissected from periphery to center using femtosecond laser. Central zone remains untouched. A large diameter full-thickness trepanation is performed and the donor cornea is divided into the anterior and posterior layers. The ICCR is put on the donor cornea while holding the posterior layer with forceps. Penetrating or lamellar recipient bed is prepared, then the corneal graft is fixed with sutures. Transparent corneal graft acceptance does not guarantee high visual acuity due to post-keratoplasty astigmatism. Surgical correction of astigmatism is performed in the long term post-operatively and isn't effective enough. We proposed this new surgical technique of keratoplasty with simultaneous implantation of ICCR and ICRS into the graft as close as possible to the visual axis of the eye, which can help make the postoperative astigmatism minimal both immediately after surgery and in the long term. The study proposes a new approach to intraoperative prevention of post-keratoplasty astigmatism. The technique is simple, safe and effective. Analysis of long-term outcomes is required before recommending this method for widespread use in clinical practice.

[Staging of aniridia-associated keratopathy]. / Az aniridiához társult keratopathia stádiumbeosztása.

INTRODUCTION: Congenital aniridia is a rare panocular disease that affects almost all eye structures leading in most patients to reduced visual acuity. Ophthalmological signs include aniridia-associated keratopathy, secondary glaucoma, cataract, macular and optic nerve head hypoplasia, nystagmus. Although the term aniridia-associated keratopathy has long been used in the literature, various staging proposals have been described. OBJECTIVE: To analyze aniridia-associated keratopathy stages, using available literature classifications, in patients with aniridia in Hungary. PATIENTS AND METHODS: We examined 65 eyes of 33 patients with congenital aniridia (age: 25.69 ± 17.49 [5-59] years, 17 females [51.51%]). We recorded the corneal status by slit-lamp examination and classified the corneal abnormalities according to the Mackman, Mayer, López-García and Lagali staging. RESULTS: According to Mackman's classification, 8 eyes (12.3%) were in stage 0, 0 eye in stage 1A, 38 eyes (58.46%) in stage 1B and 19 eyes (29.23%) in stage 2. According to Mayer, stage I included 8 eyes (12.3%), stage II 38 eyes (58.46%), stage III 5 eyes (7.7%), stage IV 7 eyes (10.77%) and stage V 7 eyes (10.77%). In López-García's classification, 8 eyes (12.3%) could not be grouped, 20 eyes (30.77%) were in stage 1, 18 eyes (27.7%) in stage 2 and 19 eyes (29.3%) in stage 3. Lagali's classification included 8 eyes (12.3%) in stage 0, 20 eyes (30.77%) in stage 1, 18 eyes (27.7%) in stage 2, 5 eyes (7.7%) in stage 3 and 14 eyes (21.54%) in stage 4. CONCLUSION: We recommend using Lagali's staging scheme for aniridia-associated keratoptahy due to its ease of use, detailed progression assessment, and treatment planning. In stage 1 according to Lagali, blood vessels cross the limbus by up to 1 mm, in stage 2 the central 2-3 mm of the corneal area is spared of blood vessels. When the blood vessels reach the center of the cornea, it is stage 3, followed by opaque, uneven corneal pannus in stage 4. Orv Hetil. 2023; 164(27): 1063-1069.

Intra-operative optical coherence tomography in corneal lamellar graft reinforcement for Boston type I keratoprosthesis corneal melt.

Corneal melt is a sight-threatening complication of Boston type 1 keratoprosthesis (KPro). Severe corneal melt may result in hypotony, choroidal hemorrhage, and even spontaneous extrusion of the KPro, which may lead to a poor visual prognosis. Lamellar keratoplasty is one surgical option for the management of mild corneal melt, especially when a new KPro is not available. Herein, we present a new surgical technique application, intra-operative optical coherence tomography (iOCT) for the management of cornea graft melt after Boston type 1 KPro implantation. The visual acuity and the intra-ocular maintained stable at 6 months post-operatively, and the KPro remained in place without corneal melting, epithelial ingrowth, or infection. iOCT may prove to be a real-time, non-invasive, and accurate treatment for corneal lamellar dissection and suturing beneath the anterior plate of the KPro, which can effectively help the surgeon to make surgical decisions and reduce post-operative complications.

Endothelial dysfunction of the cornea after exposure to sprayed venom from hornets.

PURPOSE: Ocular injuries due to Hymenoptera venom are uncommon and most injuries occur on the ocular surface. We reported two rare cases of corneal endothelial damage caused by hornet venom that was sprayed, not injected, through stinging in the eye. OBSERVATIONS: Case 1: A 57-year-old male patient was injured when a hornet sprayed venom into his left eye. He was referred to our hospital because the edoema and epithelial erosion of the cornea persisted. The patient presented with bullous keratopathy, asymmetrical iris atrophy, irreversible mydriasis, and glaucoma. His cataract progressed, and his best-corrected visual acuity was 0.03. Cataract surgery was performed after anti-inflammatory treatment with steroids, and Descemet-stripping automated endothelial keratoplasty was performed 6 months later. The patient recovered well postoperatively: his best-corrected visual acuity improved to 1.0 and he continued his glaucoma treatment. Case 2: A 75-year-old male patient had damage to his corneal epithelium, severe conjunctivitis, and conjunctival edoema when sprayed hornet venom entered his left eye. At initial presentation, the corneal endothelial cell density had decreased to 1042 cells/mm2. The conjunctival sac was washed, and steroid and topical antibacterial instillations were administered. His best-corrected visual acuity improved from 0.07 at the initial visit to 0.5. However, the corneal opacification and glaucoma persisted, and 3 months later the corneal endothelial cell density decreased to 846 cells/mm2. CONCLUSIONS AND IMPORTANCE: Corneal injuries caused by sprayed hornet venom are rare; however, they can cause intense anterior chamber inflammation and severe, irreversible corneal endothelial damage. In such cases, prompt initial treatment, the administration of adequate anti-inflammatory medication, and careful evaluation of the corneal endothelium are required.

[Corneal ectasia following small-incision lenticule extraction: a case report].

A 22-year-old male presented with complaints of blurred vision in his right eye over the past 2 years following small incision lenticule extraction (SMILE) surgery conducted 4 years ago. Following a thorough ocular examination and evaluation, he was diagnosed with corneal ectasia in the right eye after the SMILE procedure. Subsequently, the patient underwent corneal cross-linking (CXL) treatment in the right eye to prevent the progression of the condition. After 3 months of treatment, the corneal ectasia remained stable. This article outlines the process of diagnosis and treatment, reviews the corneal conditions prior to the SMILE surgery, and analyzes the possible reasons behind the occurrence of postoperative corneal ectasia.