One Incremental Stride for Doxycycline, One Substantial Advancement for Thyroid Eye Disease.

The aim of this study is to assess the effectiveness of a 12-week doxycycline treatment for thyroid eye disease (TED), an autoimmune condition associated with thyroid dysfunction. In this randomized controlled clinical trial, 82 patients were randomly assigned at a 1:1 ratio to receive doxycycline (50 mg) or to undergo no treatment. Various metrics, including margin reflex distance (MRD1 and MRD2), eyelid aperture, levator muscle function, lagophthalmos, proptosis, ocular motility, diplopia, and Graves' ophthalmopathy-specific quality-of-life (GO-QOL) scale scoring were assessed. Exclusion criteria were uncontrolled systemic diseases, tetracycline allergies, pregnancy, lactation, or age below 18. The mean age was 51.6 years (SD), 87.8% of participants were female, and all were Caucasians. By week 12, the doxycycline group exhibited a significant improvement rate based on MRD2 (from 4 to 15 participants with physiological findings), clinical activity score (from 7 to 35 participants with non-active disease), and GO-QOL (from 51.22% to 70.73% of participants with a good life quality). Doxycycline showcased anti-inflammatory and immunomodulatory effects in treating TED, suggesting its potential efficacy for TED and other orbit inflammatory conditions. However, these results warrant further validation through future research involving extended follow-up periods and larger cohorts.

Masqueraded sebaceous gland carcinoma of the lower eyelid in a young pregnant patient.

The purpose of this case report is to present misdiagnosed sebaceous gland carcinoma of the lower eyelid with rapid growth in a young woman during pregnancy. Eyelid sebaceous gland carcinoma is a relatively rare tumor and a disease primarily of older patients. It occurs more commonly in oriental populations and with a predilection for the upper eyelid. Early diagnosis and appropriate treatment may help improve disease control and patient survival.

Solitary Clear Cell Renal Cell Carcinoma Metastasis to the Eyelid: A Case Report.

Introduction: This study is a case of solitary clear cell renal cell carcinoma (ccRCC) eyelid metastasis in a 66-year-old man as the first sign of a primary tumor. ccRCC usually spreads to the lungs, mediastinum, bones, liver, and brain, while ocular metastases are rare. Case Presentation: Solitary metastasis presented as a solid mass in the central third of the upper eyelid, which has been growing for 3 weeks. Treatment included tumor removal and blepharoplasty. Histopathological examination showed metastasis of clear cell renal carcinoma. A thorough examination revealed a primary tumor on the lower pole of the right kidney. A right nephrectomy was performed, and histopathology showed ccRCC. Postoperative examinations showed no signs of local or systemic disease. Sunitinib malate was administered to the patient. Conclusion: The eyelid metastasis in this case was still solitary and had been discovered before the existence of the primary tumor was known. Ocular metastasis of renal carcinoma is a rare initial manifestation of the disease and therefore requires a multidisciplinary approach in the treatment of these patients.

Correlation between Structural and Functional Changes in Patients with Raised Intraocular Pressure Due to Graves' Orbitopathy.

This study explores the complication of secondary intraocular pressure (IOP) elevation and consequent glaucoma development in Graves' orbitopathy (GO), an autoimmune disorder associated with hyperthyroidism. Utilizing Octopus 900 visual field testing and optical coherence tomography (OCT), the research established correlations between functional and structural changes in optic nerve regions in patients with GO and patients with GO with elevated IOP (GO IOP) groups. A comparison with primary open-angle glaucoma (POAG) was conducted in a cohort of 182 subjects. The study identifies optic nerve head parameters that effectively differentiate changes in GO and GO IOP groups. In the GO group, the strongest correlation between structural and functional changes was observed in sector 7, while in the GO IOP group, it was in sectors 1 and 7. For POAG, correlation was found in six sectors. Elevated IOP in GO correlates with structural and functional impairments similarly to early glaucoma. Risk factors for GO-related elevated IOP included older age, longer duration of thyroid disease, and higher anti-thyroglobulin values. The study highlights the significance of regular IOP measurements, visual field assessments, and OCT examinations in GO patients. Early antiglaucoma intervention is warranted when characteristic structural and functional changes and/or risk factors are identified.

New characterization and safety evaluation of human limbal stem cells used in clinical application: fidelity of mitotic process and mitotic spindle morphologies.

BACKGROUND: Limbal stem cells (LSCs) are crucial for the regeneration of the corneal epithelium in patients with limbal stem cell deficiency (LSCD). Thus, LSCs during cultivation in vitro should be in highly homogeneous amounts, while potency and expression of stemness without tumorigenesis would be desirable. Therefore, further characterization and safety evaluation of engineered limbal grafts is required to provide safe and high-quality therapeutic applications. METHODS: After in vitro expansion, LSCs undergo laboratory characterization in a single-cell suspension, cell culture, and in limbal grafts before transplantation. Using a clinically applicable protocol, the data collected on LSCs at passage 1 were summarized, including: identity (cell size, morphology); potency (yield, viability, population doubling time, colony-forming efficiency); expression of putative stem cell markers through flow cytometry, immunofluorescence, and immunohistochemistry. Then, mitotic chromosome stability and normal mitotic outcomes were explored by using live-cell imaging. Finally, impurities, bacterial endotoxins and sterility were determined. RESULTS: Expression of the stemness marker p63 in single-cell suspension and in cell culture showed high values by different methods. Limbal grafts showed p63-positive cells (78.7 ± 9.4%), Ki67 proliferation (41.7 ± 15.9%), while CK3 was negative. Impurity with 3T3 feeder cells and endotoxins was minimized. We presented mitotic spindles with a length of 11.40 ± 0.54 m and a spindle width of 8.05 ± 0.55 m as new characterization in LSC culture. Additionally, live-cell imaging of LSCs (n = 873) was performed, and only a small fraction < 2.5% of aberrant interphase cells was observed; 2.12 ± 2.10% of mitotic spindles exhibited a multipolar phenotype during metaphase, and 3.84 ± 3.77% of anaphase cells had a DNA signal present within the spindle midzone, indicating a chromosome bridge or lagging chromosome phenotype. CONCLUSION: This manuscript provides, for the first time, detailed characterization of the parameters of fidelity of the mitotic process and mitotic spindle morphologies of LSCs used in a direct clinical application. Our data show that p63-positive CK3-negative LSCs grown in vitro for clinical purposes undergo mitotic processes with extremely high fidelity, suggesting high karyotype stability. This finding confirms LSCs as a high-quality and safe therapy for eye regeneration in humans.

Cataract surgical training in Europe: European Board of Ophthalmology survey.

PURPOSE: To survey recently graduated European ophthalmologists concerning cataract surgery (CS) training opportunities. SETTING: Countries affiliated to the European Board of Ophthalmology (EBO). DESIGN: Cross-sectional study of anonymous survey results. METHODS: A 23-question online survey was emailed to candidates who sat the EBO Diploma Examination as residents between 2018 and 2022. RESULTS: 821 ophthalmologists from 30 countries completed the survey. The mean residency duration was 4.73 (SD 0.9) years. The mean reported number of entire CS procedures performed was 80.7 (SD 100.6) at the end of residency, but more than 25% of respondents (n = 210) had received no live CS training during their residency. The self-confidence (scale, 1 to 10) to perform a simple case or challenging case, manage posterior capsular rupture, and realize a corneal stitch were rated 4.1, 3.2, 4.2, 2.4, respectively. We observed extensive variation in clinical exposure to CS and self-reported confidence to perform CS between European trainees. Females reported a mean of 18% fewer entire procedures than their male colleagues and were also less confident in their surgical skills (P < .05). Trainees in residency programs longer than 5 years performed fewer procedures and were less confident than trainees in residences of shorter duration (P < .001). The importance of fellowships to complete surgical education was rated 7.7 out of 10. CONCLUSIONS: CS training across European countries lacks harmony. Female ophthalmology trainees continue, as in other specialties, to experience apparent gender bias. European level recommendations seem necessary to raise and harmonize competency-based CS training programs and promote post-residency fellowship training programs.

The Role of Thermal Camera in the Assessment of Thyroid Eye Disease Activity.

Background: Thyroid eye disease (TED; also known as thyroid - associated orbitopathy, Graves ophthalmopathy) is an autoimmune inflammatory disease which presents in typical signs and symptoms such as deep orbital pain, chemosis with or without caruncular edema, unilateral or bilateral proptosis, eyelid retraction, eyelid edema or erythema, restrictive strabismus and compressive optic neuropathy. Objective: The aim of this study was to investigate the role of thermal camera in the assessment of thyroid eye disease (TED) activity compared to the Clinical Activity Score (CAS) scale, exophthalmometry values, and thyroid hormone and antibody levels. Methods: A total of 50 patients participated in this cross-sectional study of whom 29 were in the active phase of TED according to the sum on CAS scale and 21 patients in the inactive phase. The Flir E8® thermal camera was used to measure the temperature of the orbital area and the values were compared with the CAS scale, exophthalmometry values and thyroid hormone and antibody levels. Results: Higher values of temperature (p>0.0001), CAS score (p>0.0001), exophthalmometry (p=0.022), FT4 (p=0.0176) and TRAb (p=0.0091) were found in patients in the active phase of TED. Temperature of orbital area showed statistically significant positive correlation with CAS scale (p=0.0001), exophthalmometry values (p=0.0022) and anti-TPO levels (p=0.019). Conclusion: Thermal camera showed higher values of the temperature of the orbital area in patients in the active phase of the disease and positively correlated with the CAS scale, exophthalmometry findings and anti-TPO levels.

SURGICAL MANAGEMENT OF A PENETRATING BRAIN WOUND AND ASSOCIATED PERFORATING OCULAR INJURY CAUSED BY A LOW-VELOCITY SHARP METALLIC OBJECT: A CASE REPORT AND LITERATURE REVIEW.

Penetrating traumatic brain injury accompanied by perforating ocular injury caused by low-velocity foreign bodies is a life-threatening condition, a surgical emergency and a major challenge in surgical practice, representing a severe subtype of non-missile traumatic brain injury, which is a relatively rare pathology among civilians. Optimal management of such an injury remains controversial, requiring full understanding of its pathophysiology and a multidisciplinary expert approach. Herein, we report a case of penetrating brain and associated perforating eye injury and discuss relevant literature providing further insight into this demanding complex multi-organ injury. We present a case of 39-year-old male patient with transorbital penetrating brain and perforating ocular injury undergoing emergency surgery to remove a retained sharp metallic object from the left parietal lobe. Following appropriate and urgent diagnostics, a decompressive left-sided fronto-temporo-parietal craniectomy was immediately performed. A retained sharp metallic object (a slice of a round saw) was successfully removed, while primary left globe repair and palpebral and fornix reconstruction were performed afterwards by an ophthalmologist. A prophylactic administration of broad-spectrum antibiotics was applied to prevent infectious complications. Early postoperative recovery was uneventful. The patient was discharged on day 45 post-injury having moderate right-sided motor weakness, ipsilateral facial nerve central palsy, and light motoric dysphasia. The vision to his left eye was completely and permanently lost. In conclusion, management of non-missile transorbital penetrating brain injury can be satisfactory when proper clinical and radiologic evaluation, and amply, less radical surgical approach is performed early. A multidisciplinary routine is a prerequisite in achieving a favorable management outcome.

COMPUTER BASED EYE TRACKER FOR DETECTION OF MANIFEST STRABISMUS.

Strabismus is a common disorder in which eyes are not aligned with their optical axis, resulting in an abnormal binocular interaction, thus leading to amblyopia. Accordingly, early detection and diagnosis are mandatory. Despite technology development and constant knowledge growth, the foundations of physiology and the diagnosis of strabismus were set back in the 19th or early 20th century and have not changed since. In this paper, a novel, properly tested and evaluated eye-tracking based method for manifest strabismus diagnosis is presented. The evaluation showed the aforementioned method to have both high sensitivity and specificity in detecting manifest strabismus without the need for a skilled examiner, thus being suitable for population screening and highlighting the need for future research regarding testing of latent strabismus.

Structure-Function Relationship of Changes in Visual Field Indices with Quadrant and Average Retinal Nerve Fiber Layer Thickness in the Eyes with Exfoliation.

The progressive nature of glaucoma suggests it should be possible to detect structural changes such as retinal nerve fiber layer (RNFL) thickness loss before the condition becomes clinically apparent with visual field (VF) impairment. Therefore, the aim was to analyze RNFL thickness and VF changes in study groups with unilateral exfoliation syndrome (XFS), bilateral XFS and bilateral exfoliative glaucoma (XFG), and compare it with controls. The study included 114 subjects (228 eyes) divided into 4 groups according to the presence of exfoliation: 30 subjects with unilateral XFS (30 with clinically visible XFS and 30 fellow eyes), 24 subjects (48 eyes) with bilateral XFS, 28 (56 eyes) subjects with bilateral XFG, and control group (32 subjects). All subjects underwent VF and RNFL measurements after ophthalmologic examination. Both eyes of unilateral XFS (clinically -visible and fellow eye) showed positive correlation between Mean Defect (MD) and square root of Loss of Variance (sLV) and between MD and inferior quadrant RNFL thickness. In bilateral XFS and XFG, there was negative correlation between MD and inferior quadrant RNFL thickness. Inferior, superior and nasal quadrant RNFL thickness was lower in XFG group than in other groups. In bilateral XFS group, the inferior quadrant RNFL thickness was lower as compared with unilateral XFS group (in both eyes). The mean RNFL thickness negatively correlated with MD in bilateral XFS and XFG groups. In conclusion, structural changes before VF impairment have an important role in early detection of glaucoma in subjects at risk.

The Resident Surgeon Phacoemulsification Learning Curve at Clinical Department of Ophthalmology, Sestre Milosrdnice University Hospital Center

The aim of the study was to analyze the resident learning process of phacoemulsification cataract surgery and to assess the resident phacoemulsification learning curve. This prospective study comprised 86 consecutive cases of phacoemulsification performed using standard technique by eight residents over a one-year period at Clinical Department of Ophthalmology, Sestre milosrdnice University Hospital Center in Zagreb. Operative data on each case included resident and attending surgeon, date of operation, step-by-step success questionnaire, and intraoperative complications. Postoperative data included visual acuity at one-month postoperative visit and postoperative complications. Eighty-six operations were performed under the supervision of attending surgeon. The mean best-corrected visual acuity improved from 0.47±0.25 to 0.8±0.25 postoperatively. Intraoperative complications occurred in 13 (15.12%) cases and continued to decrease throughout residency training. The mean number of individually performed steps per operation increased throughout residency (from 7.6 to 9.0). There was one early postoperative complication, endophthalmitis, which was successfully treated, and no other postoperative complications occurred. Resident surgical competency can be improved by maximizing the number of cataract procedures since the complication rates and the number of individually performed steps improved continuously with increasing surgical experience.

Epithelioid hemangioma of the orbit: case report.

Epithelioid hemangioma (EH) and Kimura's disease (KD) were once considered different stages of the same disease, as they share many clinical and histopathologic similarities. Nowadays, they are considered as two different entities, but some authors still confuse these terms. Our objective is to present a case of EH occurring in a very uncommon location and to emphasize the microscopic and clinical differences between EH and KD. We present a case of EH of the orbit in an 83-year-old man diagnosed after histopathologic evaluation of a mass that was surgically removed from the orbit. The tumor showed typical microscopic appearance with pathognomonic epithelioid endothelial cells. The diagnosis was also confirmed by immunohistochemical analysis. Our case clearly illustrates typical appearance of EH and the main differences between EH and KD are thoroughly discussed.

Perforating corneal injury in rat and pentadecapeptide BPC 157.

Based on its healing effects in various tissues, we hypothesized that the stable gastric pentadecapeptide BPC 157 heals corneal ulcerations in rats and effects corneal transparency. We made a penetrant linear 2-mm incision in the paralimbal region of the left cornea at the 5 o'clock position with a 20-gauge MVR incision knife at 45° under an operating microscope. Medication was BPC 157 (2 pg/mL, 2 ng/mL, and 2 µg/mL distilled water, two eye drops/left rat eye) immediately after injury induction and then every 8 h up to 120 h; controls received an equal volume of distilled water. In contrast to the poor healing response in controls, BPC 157 significantly accelerated the healing process in 2 µg and 2 ng BPC 157-treated eyes, starting 24 h after the injury, and the fluorescein and Seidel tests became negative. The epithelial defects were completely healed at 72 h (2 µg BPC 157-treated group) and at 96 h (2 ng BPC 157-treated group) after injury. Aqueous cells were absent at 96 h and 120 h after injury in the 2 µg and 2 ng BPC 157-treated groups, respectively. In conclusion, BPC 157 effects the rapid regaining of corneal transparency. Whereas controls developed new vessels that grew from the limbus to the penetrated area, BPC 157-treated rats generally had no new vessels, and those that did form in the limbus did not make contact with the penetrated area. Thus, BPC 157 eye drops successfully close perforating corneal incisions in rats.

Retinal nerve fibre layer thickness measurements after successful retinal detachment repair with silicone oil endotamponade.

AIMS: To measure peripapillary retinal nerve fibre layer thickness (RNFL) by using spectral domain optical coherence tomography (OCT) in patients who underwent successful retinal detachment repair with silicone oil tamponade. METHODS: Sixty patients treated with pars plana vitrectomy and silicone oil tamponade for retinal detachment were prospectively enrolled in a study. Peripapillary RNFL thickness was measured with a Cirrus HD-OCT at 7, 30, 90 and 180 days postoperatively, using an Optic Disc Cube 200×200 protocol. The fellow eye of each study patient served as a control. Median peripapillary RNFL thickness in silicone oil filled eyes was compared with control eyes. RESULTS: The median RNFL thickness in the group of vitrectomised eyes was significantly higher compared with control eyes at every visit. The analysis of variance showed that the median thickness in vitrectomised eyes differed between visits (F=4,3023; p=0.006). There was no time-related trend for RNFL thickness in this group. The analysis of variance of RNFL thickness in the fellow, unoperated eyes showed no difference between visits (F=2,3426; p=0.075). CONCLUSIONS: In patients with silicone oil tamponade, peripapillary RNFL was significantly thicker in comparison with fellow unoperated eyes over a 6-month period. TRIAL REGISTRATION NUMBER: NCT 01255306.

Astigmatism and diagnostic procedures.

Astigmatism represents an inability of the cornea and lens to provide a sharp image onto the retina. Correcting astigmatic errors, whether congenital, contact lens induced or surgically induced, is now an integral part of modern cataract and refractive procedures. Development of modern technology has enabled accurate diagnosis and perfect opportunities for correction; however, while cataract and keratorefractive surgery have come a long way in the last decade, the treatment and diagnosis of astigmatism continue to challenge ophthalmologists. There are several diagnostic procedures and tools available today, some standard and some contemporary that include keratometry, corneal topography, apparatus using wavefront or Scheimpflug analysis like Orbscan, Pentacam, Wavescan, etc. With the introduction of several new diagnostic tools, measurements of astigmatism have become less of an issue, but in some cases it is still difficult to obtain consistent results. What remains still unanswered is the question of the best diagnostic tool on the market. Further research is needed to evaluate both tools as well as their clinical application for optimal use.

Limbal relaxing incision during cataract surgery.

Limbal relaxing incisions are one of the more commonly performed procedures with phacoemulsification to correct preexisting astigmatism during cataract surgery. The aim of the study was to evaluate the effect and stability of limbal relaxing incisions in reducing preexisting astigmatism at the time of phacoemulsification. The study included 10 eyes in 12 patients who underwent limbal relaxing incisions during cataract surgery, with preexisting astigmatism of 1-2 diopter (D). Assessments were made preoperatively, and 1 and 3 months postoperatively. Outcome measures included uncorrected distance visual acuity, best corrected distance visual acuity and keratometric astigmatism measures. The mean preoperative and postoperative refractive astigmatism was 1.50 D (+/- 0.75D) and 0.25 D (+/- 0.25 D), respectively. There were no serious postoperative complications. Limbal relaxing incisions provide a viable option for correcting preexisting astigmatism at the time of cataract surgery with mild complications.

Toric intraocular lens implantation for astigmatism correction in cataract surgery.

The aim of this study was to evaluate clinical outcomes after toric intraocular lens implantation for astigmatism correction in patients undergoing cataract surgery. This prospective observational study included eyes undergoing cataract surgery at Sestre milosrdnice University Hospital Center between February and September 2011. The study enrolled eyes that had visually significant cataract and preexisting regular corneal astigmatism of 1.50 D or greater. Phacoemulsification was performed and all eyes received an AT TORBI 709 M toric foldable intraocular lens. At 3 months, the uncorrected distance visual acuity was 0.8 or better in 9 of 10 eyes. At 3 months postoperatively, the median reduction in refractive cylinder was statistically significant (P < 0.05). The median intraocular lens axis rotation was 3.0 degrees interquartile range (2.0-4.0 degrees). Our results showed AT TORBI 709 IOL to be an effective surgical option to correct preexisting corneal astigmatism and spectacle dependence after cataract surgery.