Salubrinal Ameliorates Inflammation and Neovascularization via the Caspase 3/Enos Signaling in an Alkaline-Induced Rat Corneal Neovascularization Model.

Background and Objectives: Ocular alkaline burn is a clinical emergency that can cause permanent vision loss due to limbal stem cell deficiency and corneal neovascularization (CNV). Although the basic pathogenetic mechanisms are considered to be acute oxidative stress and corneal neovascularization triggered by inflammation, the underlying intracellular mechanisms have not been clearly elucidated. The aim of this study was to investigate the role of endoplasmic reticulum (ER) stress on inflammation and neovascularization, and the effect of the ER stress inhibitor salubrinal (SLB), as a novel treatment in a corneal alkaline burn model in rats. Methods: Chemical burns were created by cautery for 4 s using a rod coated with 75% silver nitrate and 25% potassium nitrate in the corneal center for the corneal neovascularization (CNV) model. Twenty-eight Wistar albino rats were divided into four groups: SHAM, CNV, CNV + SLB, and CNV + bevacizumab (BVC). After the CNV model was applied to the right eye, a single subconjunctival dose (0.05 mL) of 1 mg/kg salubrinal was injected into both eyes in the CNV + SLB group. A total of 1.25 mg/mL of subconjunctival BVC was administered to the CNV + BVC group. Fourteen days after experimental modeling and drug administration, half of the globes were placed in liquid nitrogen and stored at -20 °C until biochemical analysis. The remaining tissues were collected and fixed in 10% buffered formalin for histopathological and immunohistochemical analysis. Three qualitative agents from three different pathways were chosen: TNFR for inflammation, endothelial nitric oxide synthase (e-NOS) for vascular endothelial growth factor (VEGF)-mediated vascular permeability, and caspase-3 for cellular apoptosis. Results: Significantly lower caspase-3 and eNOS levels were detected in the CNV + SLB and CNV + BVC groups than in the CNV group. Additionally, histopathological evaluation revealed a significant decrease in neovascularization, inflammatory cell infiltration, and fibroblast activity in the CNV + SLB and CNV + BVC groups. The endoplasmic reticulum stress inhibitor, salubrinal, administered to the treatment group, attenuated apoptosis (caspase-3) and inflammation (e-NOS). In the control group (left eyes of the SLB group), salubrinal did not have a toxic effect on the healthy corneas. Conclusion: The ER stress pathway plays an important role in angiogenesis after alkaline corneal burns, and treatment with SLB modulates this pathway, reducing caspase-3 and eNOS levels. Further studies are needed to understand the molecular mechanisms altered by SLB-mediated therapy. The fact that more than one mechanism plays a role in the pathogenesis of CNV may require the use of more than one molecule in treatment. SLB has the potential to affect multiple steps in CNV pathogenesis, both in terms of reducing ER stress and regulating cellular homeostasis by inhibiting the core event of integrated stress response (ISR). Therefore, it can be used as a new treatment option and as a strengthening agent for existing treatments. Although blockade of intracellular organelle stress pathways has shown promising results in experimental studies, more in-depth research is needed before it can be used in routine practice. To the best of our knowledge, this study is the first to report the role of ER stress in corneal injury.

The Possible Protective Effect of Boric Acid in an Alkaline-Induced Corneal Neovascularization Rat Model.

It is known that boric acid (BA) exerts it antioxidant and anti-inflammatory effects by activating the activating transcription factor 4 (ATF4) and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. This pathway has been reported to control antioxidant status in the eye. The aim of this study was to investigate the possible preventive effects of boric acid administration on oxidative damage and corneal neovascularization (CNV). Sixteen adult female Wistar albino rats were divided into two groups: (I) control (n = 8); the CNV model was applied to the right eye of the rats, and the left eyes were used as healthy controls. (II) CNV + BA (n = 8): After the CNV model was applied to the right eyes, a single subconjunctival dose (0.05 mL) of 0,018 g/mL BA was injected into the right and left eyes of the rats. Biochemical, histopathological, and immunohistochemical analyses were performed. Moderate VEGF positivity was observed in the vessels of the CNV group, a decrease in vessel proliferation, and weak VEGF positivity in the CNV + BA group. The TAS level in the CNV + BA group was significantly higher than that in the other groups. The TOS level was significantly higher in all groups than it is in the control group. The OSI value was increased in all groups when compared to the control group, but only the CNV and BA groups were statistically significant. BA not only reduced alkaline-induced corneal damage histologically but also showed a protective effect on oxidative stress biochemically.

Comparison of obstructive sleep apnea syndrome and keratoconus patients on elevation maps.

PURPOSE: This study aimed to compare the tomographic features of the cornea on elevation maps between obstructive sleep apnea syndrome (OSAS) and keratoconus (KC) patients and to investigate the presence of susceptibility to ectatic corneal diseases in OSAS patients. DESIGN: This is a comparative cross-sectional case-control study. METHODS: This study included 84 eyes of 42 patients diagnosed with severe OSAS using polysomnography (apnea/hypopnea index > 30), 84 eyes of 56 patients diagnosed with keratoconus, and 84 eyes of 42 healthy subjects as control group and evaluated in three groups. Elevation maps of all the groups were performed using Pentacam, and topometric, pachymetric, and deviation indices were recorded. RESULTS: The study included 252 eyes of 130 participants divided in three groups. Comparing all the tomographic keratometric values, a significant difference was found among the three groups. All keratometric values were found to be higher in the OSAS patients group compared to those in the control group. Also topometric indices and Belin-Ambrosio enhanced ectasia display (BAD) were observed to be higher as in subclinical keratoconus and statistically significant when compared to those in the control group. CONCLUSION: The study reveals the tomographic corneal characteristics and topometric and pachymetric indices of patients with severe OSAS at the time of diagnosis; these findings statistically significantly differ from the control group. In addition to the known association of floppy eyelid in OSAS patients, the suspicion of keratoconus should be kept in mind.

The usability of lamellar scleral autograft in ocular perforation treatment.

IMPORTANCE: Open globe injury is a frequent and preventable healthcare problem with an annual incidence of 3.5/100,000 worldwide. Management and treatment methods aim to ensure globe integrity. Unfortunately, it is not possible to achieve globe integrity in some of the cases, and these can result in poor visual outcomes. PURPOSE: To evaluate the usability of lamellar scleral graft in the repair of ocular perforations. METHODS: This was a retrospective review of 11 patients who underwent lamellar scleral graft surgery for ocular perforation between June 2015 and June 2020. Due to the failure of the repairs when other techniques were used, the perforation zones were sealed with lamellar scleral autografts. The primary measures of the outcomes were globe integrity, postoperative best corrected visual acuity, and intraocular pressure (IOP). Visual acuity was determined using the Snellen eye chart, and IOP was measured using the automated pneumatic tonometry during standard examination. RESULTS: The participants enrolled in this study included 11 patients who underwent lamellar scleral patch graft between 2015 and 2020. The mean age of the patients was 58.81 ± 16.6 years (range, 16-77), and the mean follow-up period was 12.5 ± 3.8 months (range, 8-20). During the surgery, the perforation zone was treated and no leakage was observed. IOP significantly increased, and visual acuity improved in almost all eyes. The factors that made it necessary to use scleral grafts in patients were star-shaped wounds, delayed presentation, lost corneal / scleral tissue. CONCLUSION: Lamellar scleral graft is a method that can be used in the treatment of defective ocular perforation with acceptable complications and provides adequate functional and structural stability. Scleral patch grafting can be considered as an alternative option for surgeons treating a variety of ocular conditions that cause tectonic imbalance or poor cosmesis.

Evaluation of Anterior Segment Parameters During Pregnancy.

PURPOSE: To evaluate the anterior segment changes of eye during pregnancy according to the trimesters and compare them with non-pregnant subjects. MATERIALS AND METHODS: This prospective study included 90 pregnant women (1.trimester: 30, 2.trimester: 30, 3.trimester: 30 pregnants) and 30 non-pregnant women whose ages ranging from 20 to 40 years. Intraocular pressure (IOP) and keratometry values were measured. Corneal thickness (CT) measurements were performed from pupil center, corneal apex and thinnest point of cornea. In addition, anterior chamber volume (ACV), anterior chamber depth (ACD) and anterior chamber angles (ACA) were also measured. RESULTS: All trimester groups (1, 2 and 3.trimester) were compared with non-pregnant women for all measured parameters. The mean IOP values were significantly lower in 2nd and 3rd trimesters (p˂0.05). The differences of keratometric and CT measurements were not statistically significant in pregnant women when compared with non-pregnant women (p > .05). ACV was significantly higher in 1st trimester (p˂0.05); the difference of ACV in 2nd and 3rd trimesters was not significant (p > .05). There was also no significant difference in ACD and ACA measurements in trimester groups when compared with non-pregnants (p > .05). CONCLUSIONS: We found that IOP decreased in 2nd and 3rd trimesters, and ACV increased in 1st trimester of pregnancy when compared with non-pregnant women. If the physiological changes in pregnancy are well known, diseases that affect anterior segment such as glaucoma and corneal disorders will be managed more accurately.

A Case of Shield Ulcer Due to Vernal Keratoconjunctivitis.

Corneal shield ulcer is an uncommon but serious complication of vernal keratoconjunctivitis (VKC) that can threaten visual acuity. We present a 12-year-old case with a corneal shield ulcer on the superior part of the cornea in the right eye. We learned from his history that he was treated with topical cyclosporine A (CsA) and corneal debridement was performed for the same complaints six months ago. His complaints recurred six months after ceasing topical CsA voluntarily. Topical anti-allergic and CsA treatments were commenced, we also performed corneal debridement. During his follow-ups, the corneal ulcer healed leaving a scar as opacity and neovascularization. This case highlights the role of the anti-inflammatory effect of CsA in preventing the recurrence of shield ulcers.

Paralytic Strabismus in Turkish Children Examined at Three Tertiary Care Services: A Retrospective Cohort Study.

PURPOSE: To assess the etiology and distribution of pediatric ocular motor nerve palsy manifesting as paralytic strabismus. METHODS: The authors retrospectively examined the medical files of patients younger than 18 years who were suspected to have strabismus between January 1999 and June 2012 in three Turkish clinics and followed up for at least 6 months. Patients with paralytic strabismus were stratified according to age, sex, affected cranial nerve, and etiology (congenital, traumatic, neoplastic, post-viral, vascular, undetermined, or other), and compared the proportions between groups. RESULTS: Paralytic strabismus was observed in 33 of 1,263 patients (2.6%), with a mean age of 5.9 ± 4.4 years (range: 6 months to 16 years). Seventeen patients (51.5%) were boys and 16 (48.5%) were girls. Twelve patients (36.4%) had congenital paralytic strabismus, and 21 patients (63.6%) had acquired strabismus. The most prevalent cause of acquired paralytic strabismus was trauma in 11 patients (52.4%), undetermined in 6 patients (28.6%), post-viral cranial nerve paralysis in 3 patients (14.3%), and a history of hydrocephalus in 1 patient (9.1%). The fourth cranial nerve was the most frequently affected (45.5% [15 of 33]), followed by the sixth (39.4% [13 of 33]) and the third (15.2% [5 of 33]). CONCLUSIONS: Evaluating the incidence and etiology of paralytic strabismus in children in a clinical setting may improve disease management and reduce unnecessary invasive examinations. This study will assist clinicians in understanding the clinic-based distribution of pediatric paralytic strabismus. [J Pediatr Ophthalmol Strabismus. 2021;58(5):282-286.].

Evaluation of static and dynamic Pupillometry changes in men using Silodosin for benign prostatic hypertrophy.

BACKGROUND: Intraoperative floppy iris syndrome is a variant of the small pupil syndrome that has been observed during cataract surgery in some patients currently or previously treated with α1 adrenergic blockers. It is important for cataract surgeons to predict the probable complications preoperatively. Our study aims to evaluate the static and dynamic pupil characteristics of patients treated with silodosin-a selective α1 adrenergic blocker-for benign prostate hypertrophy (BPH) and to compare these values with healthy subjects using an automatic quantitative pupillometry system. METHODS: A total of 74 BPH patients treated with silodosin for six months (group 1) and 30 healthy subjects (group 2) were enrolled in this prospective multidisciplinary cross-sectional study. Static and dynamic pupillometric measurements were obtained under optimized conditions, and the results were compared between the two groups. RESULTS: Seventy-four male patients with a mean age of 63,35 ± 7,21 (46-77) years with BPH treated with silodosin and 30 normal male subjects with a mean age of 63,07 ± 4,73 (52-71) years were analyzed. There were statistically significant differences between the groups with regard to scotopic pupil diameter (PD), high photopic PD, and low photopic PD (p < 0.001, for each one). The patient group had statistically significant higher values of amplitude and velocity of pupil contraction and lower values of duration of pupil contraction and latency as well as duration and velocity of pupil dilation. CONCLUSION: The static and dynamic pupil characteristics of subjects treated with silodosin for BPH are different from those of healthy eyes. In addition, our results may have shed light on the risk for intraoperative floppy iris syndrome (IFIS) before cataract surgery; thus, surgeons can be alert and take precautions.

An Alternative Approach for External Drainage of Suprachoroidal Hemorrhage: Active Aspiration with Butterfly Needle.

Purpose: To describe a novel surgical technique for external drainage of choroidal detachment/suprachoroidal hemorrhage with a butterfly needle.Materials and Methods: This is a retrospective case series on six eyes with serous and/or hemorrhagic choroidal detachments due to previous intraocular surgery or perforating ocular trauma that underwent active external suprachoroidal fluid drainage procedure with butterfly needle. The primary outcome measures were perioperative controlled fluid discharge and presence of choroidal detachment at 1 week, 1 month, and 6 months postoperatively. Secondary outcome measures were postoperative visual acuity and intraocular pressure.Results: During drainage, controlled hemorrhage discharge was observed. Drainage resolved hemorrhagic choroidal detachments at 1 week postoperatively. Intraocular pressure significantly increased, and visual acuity improved in all eyes. No complications were noted.Conclusion: Management of hemorrhagic choroidal detachment is challenging, and external drainage can be complicated. Active aspiration of hemorrhagic material with a butterfly needle may help early resolution.

Detection of radiotherapy-related damage in head and neck cancer patients by evaluating volumetric changes in lacrimal gland, nasolacrimal duct and computed tomography attenuation changes in lens.

PURPOSE: In our study, we aimed to evaluate the change in attenuation of lens in CT images, volumetric changes, in lacrimal gland (LG) and nasolacrimal duct (NLD) of the patients receiving radiotherapy for brain or head & neck tumor. Additionally, the correlation between these changes and radiation dose data were investigated. METHODS: Patient simulation CT images and control CT images were used to evaluate the volume and attenuation changes. Pre- and post-treatment MR and CT images were used to evaluate radiation-induced volumetric alterations in NLD and LG, respectively. Radiation therapy was given to a total dose of 54-70 Gy with conventional fractionated scheme using intensity-modulated radiotherapy technique (IMRT). Dose volume parameters were evaluated via dose volume histograms (DVHs). RESULTS: Dose volume parameters, volume and densities of 59 lenses (L), 60 LG and 60 NLD of 30 patients were retrospectively assessed. The median LG volume was significantly lower in the post-treatment images (p < 0.001), whereas the median volumes of NLD in pre- and post-RT images were similar. The Hounsfield unit (HU) numbers of lenses were significantly lower on post-RT CT images (p < 0.001). No statistically significant correlation was found between dose parameters and volume or HU changes (p = 0.054-0.817). CONCLUSION: It was observed that the attenuation of lenses and lacrimal gland volume significantly lowers following radiation. However, these alterations were not found to be correlated with dose.

No Relationship between Visual Field Damage and Choroidal Thickness in Eyes with Primary Open-Angle Glaucoma.

PURPOSE: To evaluate the association between visual field damage and choroidal thickness (ChT) in subjects with primary open-angle glaucoma. METHODS: In this cross-sectional study, 115 eyes of 58 glaucoma patients and 112 eyes of 56 healthy subjects were enrolled. ChT at the fovea, 0.5 mm temporal, 1.5 mm temporal, 0.5 mm nasal, 1.5 mm nasal to the fovea, and all quadrants in the peripapillary region were analyzed. The subjects with glaucoma were further classified by Hodapp-Anderson-Parrish scores. RESULTS: There was no difference between glaucoma and healthy subjects in mean age, gender, and refractive errors. The overall average thickness of the retinal nerve fiber layer (RNFL) was significantly lower in the eyes with glaucoma compared to the normal subjects (p < 0.01) and decreased in proportion to the severity of glaucoma (normal, 99.4; no defect, 89; early, 80.4; moderate, 63.1; and severe, 51 µm). ChT measured from the foveal region, at a distance of 500 µm from the fovea (nasal and temporal), and 1,500 µm from the fovea (nasal and temporal) did not significantly vary between the two groups. As well, peripapillary ChT did not significantly differ in proportion to the severity of glaucoma (p > 0.05 for all quadrants). The RNFL and ChT measurements were not significantly correlated with any peripapillary location (|r| ≤ 0.17, p > 0.05). The visual field mean deviation/pattern standard deviation and ChT measurements were also not significantly correlated with any peripapillary and macular location (|r| ≤ 0.12, p > 0.05). CONCLUSIONS: There was no significant difference in macular and peripapillary ChT between healthy and glaucomatous eyes that differed in severity of visual field damage. This suggests that the structural features of the choroid may not be associated with severity of primary open-angle glaucoma.

Canalicular laceration (cheese wiring) with a silicone tube after endoscopic dacryocystorhinostomy: when to remove the tube?

Objective: To discuss the removal time of a nasolacrimal silicone tube stent by reporting three cases with canalicular laceration due to prolonged indwelling of the stent. Methods: This study involved three cases of nasolacrimal duct obstruction treated by endoscopic dacryocystorhinostomy with silicone tube insertion. Results: The mean indwelling time of the silicone tube was 9.3 months and all of the patients had lower canalicular laceration near the common canaliculus. One patient presented with a complaint of canthal pain, blurred vision, and epiphora while the other two patients reported no complaint. The nasal endoscopic examination revealed a narrow fibrotic ostium below the medial concha. The silicone tubes were removed. Conclusions: To increase the success rate of the operation, the removal time for nasolacrimal silicone tubes after dacryocystorhinostomy is also important. Our findings indicate that physicians should be aware of the potential problems related to prolonged intubation.

Corneal and conjunctival sensitivity in rosacea patients.

PURPOSE: To assess corneal and conjunctival sensitivity in rosacea patients. METHODS: A total of 55 patients with rosacea and 37 control subjects participated in the study. Corneal and conjunctival sensitivity was determined by Cochet-Bonnet esthesiometer. Subjective symptoms of ocular dryness were evaluated using Ocular Surface Disease Index (OSDI). Schirmer's I test (ST), tear breakup time (tBUT) and ocular surface staining with fluorescein were carried out to measure objective signs. RESULTS: The mean corneal and conjunctival sensitivity did not differ significantly between rosacea patients and controls (all p > 0.05). Schirmer's I test and tBUT were significantly reduced (p = 0.004 for OD and p < 0.001 for OS) and grade of ocular surface staining was significantly high (p = 0.018 for OD and p = 0.038 for OS) in rosacea patients. Corneal and conjunctival sensitivity did not show significant correlation with ST, tBUT, ocular surface staining (Oxford Schema), duration of rosacea and OSDI score. CONCLUSIONS: Corneal and conjunctival sensitivity did not change significantly in rosacea.

Hyaluronic acid viscoelastic medium as an aid for microsurgical venous anastomoses.

The thin-walled structure of veins leads them to stay collapsed during anastomoses, thereby the incidence of technical failures is more common than arterial anastomoses. In order to overcome this problem, we are introducing the use of viscoelastic material based on our experience on rats. Six rats were used in order to study the technical feasibility of the viscoelastic material during microsurgical vein anastomosis. End-to-end anastomoses were performed on rat jugular veins using 0.5-1 mL of the viscoelastic medium applied to the ends of the veins and surgical field under ×30 operating microscope magnification. Then 1.8% (n:3) and 3.0% (n:3) hyaluronic acid was used as a viscous medium in order to keep the vein lumens open during anastomosis. In conclusion, we have found that 3.0% hyaluronic acid viscoelastic medium facilitates microvenous anastomosis in rat. Studies involving human practice are needed for further evaluation of this technical refinement.

Central corneal thickness in patients with mild to moderate rosacea.

OBJECTIVE: We aimed to evaluate central corneal thickness (CCT) in patients with rosacea in comparison to a healthy control group and to investigate any correlations by using the Schirmer test, tear break-up time (TBUT), and disease severity. DESIGN: Prospective nonrandomized study. PARTICIPANTS: Patients with mild to moderate rosacea (n = 51) and a group of healthy individuals (n = 51) were included. METHOD: Patients were evaluated by a dermatologist; disease severity was determined and total rosacea severity score was calculated for each patient. CCT measurements were performed using ultrasonic pachymetry. Tear function tests, including Schirmer and TBUT, were also performed. RESULTS: The mean CCT value was significantly lower in patients with rosacea than in the control group (544.91 ± 29.41 µm vs 559.40 ± 24.18 µm, p = 0.003). The mean Schirmer test value was significantly lower in patients than in controls (10.54 ± 6.09 mm vs 19.13 ± 4.24 mm, p < 0.0001), and the mean TBUT was shorter in the group with rosacea than in the controls (8.32 ± 3.50 s vs 16.67 ± 5.76 s, p < 0.0001). CCT values were found to be correlated with the Schirmer test values in the rosacea group (r = 0.33, p = 0.01). CONCLUSIONS: Patients with rosacea have thinner corneas, which could be attributed to the observed deteriorated tear function parameters. Candidates for corneal photoablation surgery should be evaluated regarding rosacea disease because the postoperative period could be complicated by decreased ocular wetting and corneal thinning, even in overlooked mild forms.

Topical ophthalmic cyclosporine in the treatment of toxic epidermal necrolysis.

Aim. To describe a case of toxic epidermal necrolysis (TEN) with ocular involvement treated with topical ophthalmic cyclosporine. Case Presentation. A 20-year-old woman developed TEN following administration of carbamazepine that was prescribed for epilepsy. Ophthalmic examination revealed bilateral pseudomembranous conjunctivitis. She was hospitalized in the intensive care unit and treated with intravenous corticosteroid and immunoglobulin. Topical cyclosporine was used in combination with topical corticosteroids for ocular surface disease. Following two months of ocular treatment, she recovered without any severe ocular complication. Ocular examination at the four-month followup showed a 2 mm of symblepharon in the lower fornix as the sole pathologic finding. Conclusion. Topical ophthalmic cyclosporine may contribute to decrease the ophthalmic complications of TEN and should be considered in the acute stage of the disease.