Search Results (44)

Glaucoma is a trans-synaptic neurodegenerative disease, and the pathological increase in intraocular pressure (IOP) is a major risk factor of glaucoma. High IOP alters microstructure and morphologies of the brain tissue. Since mechanical properties of the brain are sensitive to the alteration of the tissue microstructure, we investigate how varying durations of chronic elevated IOP alter brain mechanical properties. A chronic high IOP rat model was induced by episcleral vein cauterization with subconjunctival injection of 5-Fluorouracil. At 2, 4 and 8 weeks after induction, indentation tests were performed on the brain slices to measure mechanical properties in the hippocampus, lateral geniculate nucleus and occipital lobe of both hemispheres. Meanwhile, the brain’s microstructure was assessed via F-actin and myelin staining. Compared to the blank control group, the Young’s modulus decreased in all three brain regions in the highIOP experimental groups. F-actin fluorescence intensity and myelin area fraction were reduced in the hippocampus, while β-amyloid levels and tau phosphorylation were elevated in the experimental groups. Our study provides insight into Alzheimer’s disease pathogenesis by demonstrating how chronic high IOP alters the brain’s mechanical properties. Full article

Background/Objectives: The management of ocular tumors often necessitates surgery, either alone or in combination with radiotherapy, chemotherapy, or other modalities. While crucial for tumor control, these treatments can significantly impact the ocular surface, leading to both acute and chronic complications. This review examines iatrogenic ocular surface diseases resulting from oncologic interventions, emphasizing their pathophysiology, diagnostic challenges, and management strategies. Methods: A literature review was conducted to identify studies on iatrogenic ocular surface complications associated with ocular tumor treatments. Results: Ocular surface complications include direct damage from surgical manipulation, leading to corneal opacities and persistent epithelial defects, as well as dry eye disease secondary to postoperative chemosis. These disruptions may progress to more severe conditions such as keratopathy, corneal ulcers, limbal stem cell deficiency, and stromal scarring, further impairing visual function. Structural alterations contribute to eyelid malpositions—including ectropion, entropion, round eye, and lagophthalmos—which exacerbate exposure-related damage and ocular surface instability. In cases of uveal melanomas, the exposure of episcleral brachytherapy plaques can induce chronic conjunctival irritation, promoting adhesion formation and symblepharon. Surgical interventions disrupt ocular surface homeostasis, while radiotherapy and chemotherapy exacerbate these effects through cytotoxic and inflammatory mechanisms. Conclusions: Preventing and managing iatrogenic ocular surface complications require a multidisciplinary approach involving early diagnosis, personalized treatment strategies, and targeted postoperative care. Comprehensive pre- and postoperative planning is essential to optimize both visual function and long-term ocular surface integrity, ultimately ensuring a balance between oncologic control with functional and aesthetic preservation. Full article

Inflammatory bowel disease (IBD) is a complex, multisystemic disease and is associated with ocular pathology in 4–12% of patients. In general, ocular disease affects Crohn’s patients more frequently than those with ulcerative colitis. Episcleritis and uveitis are the most common presentations, with episcleritis often correlating with IBD flares, whereas uveitis presents independently of IBD activity and, in some cases, may even alert clinicians to a new diagnosis of IBD. Corneal EIMs encompass a range of pathologies, such as the common and benign keratoconjunctivitis sicca (dry eye disease), which nevertheless causes significant patient discomfort, and the rarer condition of peripheral ulcerative keratitis, which warrants urgent review due to the risk of corneal perforation. Alongside EIMs, clinicians should also be aware of the iatrogenic consequences to the eye following treatment of IBD. Corticosteroids may cause cataracts, glaucoma, and—indirectly via hyperglycaemia—diabetic retinopathy. Methotrexate is irritating to ocular tissues and may cause conjunctivitis and blepharitis. Biologic medications, such as anti-TNFα agents, overlap in their use as treatment of both IBD and uveitis, and yet in some patients may also increase the risk of acute uveitis flares, as well as opportunistic, sight-threatening infections. With integrated care between gastroenterology and ophthalmology, patient outcomes can be improved by facilitating earlier detection and management of ocular disease. This narrative review summarises the ocular extraintestinal manifestations of IBD, including pathophysiology, epidemiology, and current treatment strategies. Full article

Background: Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, primarily affects the gastrointestinal tract. Additionally, extraintestinal manifestations may occur in the liver, musculoskeletal system and eyes. Its etiology remains unknown, and further research is required in order to develop pharmacological drugs which achieve complete remission of the pathology. Objective: The aim of this study was to analyze the incidence of ocular extraintestinal manifestations in IBD patients. Methods: A total of six searches were carried out on the medical publication server “PubMed” in June and July 2024, using different keywords; a total of 323 results were obtained, of which 34 were finally selected for study. Results: Ocular extraintestinal manifestations in IBD patients are more common in the anterior pole of the eye, with uveitis, scleritis and episcleritis being the most usual ones. In the case of the posterior pole, the most common manifestations are posterior uveitis and optic neuritis. Conclusions: The incidence of ocular complications whose origin is inflammatory, such as uveitis, scleritis, episcleritis and neuritis, is higher than that of complications of non-inflammatory origin. Full article

Background: Ocular involvement is relatively common in granulomatosis with polyangiitis (GPA); however, choroidal involvement is rare. We present a case of serous retinal detachment resulting from choroidal involvement in GPA. Case presentation: A 55-year-old male presented to our clinic with bilateral eye redness and pain. Ocular examination revealed bilateral conjunctival injection, and dilation of the episcleral and scleral vessels. Slit-lamp examination revealed anterior chamber cells. Optical coherence tomography (OCT) confirmed serous retinal detachment (SRD) in the left eye. The patient had recently been diagnosed with GPA following a lung biopsy and had received immunosuppressive therapy, including systemic steroids, cyclosporine, mycophenolate mofetil, and rituximab. Five weeks after treatment, the clinical symptoms of the patient, including SRD, improved with alleviation of systemic symptoms. However, tapering systemic steroids and immunosuppressants and discontinuing rituximab led to disease reactivation. OCT demonstrated a recurrence of subretinal fluid, which had previously resolved, and slit-lamp examination showed mild bilateral engorged scleral vessels. Conclusions: Choroidal involvement can present as SRD and may indicate disease activity in patients with GPA. Full article

Objectives: To evaluate the long-term anatomical and functional prognosis of patients with retinal detachment (RD) secondary to acute retinal necrosis (ARN) treated with pars plana vitrectomy (PPV). Methods: This retrospective case series included 21 eyes from 21 patients with RD secondary to ARN. The study analyzed vitreous or aqueous biopsy results, the impact of antiviral therapy, time to retinal detachment, changes in visual acuity (VA), and anatomical and surgical outcomes. All cases underwent 23-gauge PPV with silicone oil tamponade, and an episcleral encircling band was used in 11 cases. All patients received systemic antiviral therapy at diagnosis. Results: Retinal reattachment was achieved in 91% of cases during follow-up, with an average follow-up period of 39.5 ± 36.8 months. The average time from ARN diagnosis to RD onset was 33.3 ± 27.5 days. VZV was detected in 10 eyes through PCR analysis. Significant differences in visual prognosis were found between macula-off and macula-on RD (p = 0.048). Eyes with optic nerve head inflammation had worse final VA (p = 0.010). No significant difference was observed between preoperative VA and VA at the end of follow-up (p = 0.665). Conclusions: VZV was the primary virus associated with ARN-related RD. Early involvement of the macula and optic nerve in retinitis negatively impacted the final visual prognosis. Full article

Background and objectives: The initial symptom that triggers granulomatosis with polyangiitis (GPA) diagnosis is rarely ocular. We describe a case with a single ocular lesion identified as probable GPA due to proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA)-positivity according to the diagnostic criteria of the Ministry of Health in Japan; the lesion repeatedly worsened. Materials and methods: A 25-year-old female visited the Department of Ophthalmology, Asahi General Hospital, with upper eyelid swelling and conjunctival and episcleral hyperemia of the left eye. Both hordeolum and eyelid cellulitis were suspected, as the condition was resistant to treatment with antibiotic eye drops. Episcleritis was suspected due to localized hyperemia in the upper part of the eye. Upon treatment with antibacterial agents and steroid eye drops, the swelling and the hyperemia repeatedly worsened every week. Results: Blood samples were positive for PR3-ANCA, and GPA with an isolated ocular lesion was considered. After oral steroid treatment, the patient had no recurrence for 4 years. There was no systemic involvement in the upper respiratory tract, lungs, or kidneys. Conclusions: Diagnosing GPA with ocular symptoms as initial manifestations is challenging. GPA should be considered in treatment-resistant eyelid, orbital, and episcleral lesions, even at a young age. Full article

Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients. Full article

The inflammatory bowel diseases (IBDs) are systemic conditions that affect not only the gastrointestinal tract but also other parts of the body. The presence of extraintestinal manifestations can significantly impact the quality of life in IBD patients. Peripheral arthritis, episcleritis, and erythema nodosum are frequently associated with active intestinal inflammation and often improve with standard treatment targeting intestinal inflammation. In contrast, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis typically occur independently of disease flares. The incidence of these conditions in individuals with IBD can reach up to 50% of patients over the course of their lifetime. In addition, some advanced therapies utilized for the treatment of IBD potentially result in side effects that may resemble extraintestinal manifestations. This review provides a thorough analysis of the pathophysiology and treatment of extraintestinal manifestations associated with Crohn’s disease and ulcerative colitis. Full article

Rhegmatogenous retinal detachment, a severe eye condition, presents anatomic separation of the neurosensory retina from its outermost layer—the retinal pigment epithelium. Early recognition of this relatively common finding and proper referral of patients to the retinal surgery department is essential in order to minimize its consequent possible severe reduction in vision. Several major surgical methods for the repair of primary rhegmatogenous retinal detachment have been in use over the last several decades, and they all aim to find and close the break in the retina that has caused the detachment. Surgery can be performed as pneumatic retinopexy, pars plana vitrectomy, and/or episcleral surgery (buckling). General surgical trends for reattaching the retina include moving from extraocular to intraocular surgery and from bigger gauge to smaller gauge via minimal invasive vitrectomy surgery (MIVS), with implementing shorter-lasting intraocular tamponades. Surgical options for rhegmatogenous retinal detachment treatment nowadays emphasize gaining retinal reattachment, preferably with one surgery and with minimum damage to the eye. The procedure should not bring secondary eye conditions and complications with severe impairment of visual acuity, and it should be performed on as much as a smaller budget, with possibly peribulbar anesthesia, enabling the patient the quickest possible recovery. It should be adjusted to the patient’s condition, not to the surgeon’s skills or preferences. Full article

We report a three-pronged phenotypic evaluation of the bioprecursor prodrug 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED) that selectively produces 17β-estradiol (E2) in the retina after topical administration and halts glaucomatous neurodegeneration in a male rat model of the disease. Ocular hypertension (OHT) was induced by hyperosmotic saline injection into an episcleral vein of the eye. Animals received daily DHED eye drops for 12 weeks. Deterioration of visual acuity and contrast sensitivity by OHT in these animals were markedly prevented by the DHED-derived E2 with concomitant preservation of retinal ganglion cells and their axons. In addition, we utilized targeted retina proteomics and a previously established panel of proteins as preclinical biomarkers in the context of OHT-induced neurodegeneration as a characteristic process of the disease. The prodrug treatment provided retina-targeted remediation against the glaucomatous dysregulations of these surrogate endpoints without increasing circulating E2 levels. Collectively, the demonstrated significant neuroprotective effect by the DHED-derived E2 in the selected animal model of glaucoma supports the translational potential of our presented ocular neuroprotective approach owing to its inherent therapeutic safety and efficacy. Full article

Background and aims: Inflammatory bowel diseases (IBD) are multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. However, a broad spectrum of extraintestinal manifestations (EIMs) is associated with IBD, affecting several organs and systems, such as the skin, musculoskeletal and hepatobiliary systems, and, not least, the eye. Approximately 10% of IBD patients can develop ocular EIMs (O-EIMs) with a higher prevalence in Crohn’s disease (CD). Eye-redness, photophobia, pain, and blurred vision are the common symptoms, with a wide rate of severity and clinical impact on the quality of life. This narrative review aims to summarize the prevalence, pathogenesis, and current evidence-based management of O-EIMs, underlying the importance of a holistic approach and specialties collaboration for a prompt diagnosis and treatment. Methods: PubMed was searched up to December 2023 to identify relevant studies investigating the pathogenesis, epidemiology, and treatment of O-EIMs in IBD patients. Results: The mechanisms underlying O-EIMs are partially unknown, encompassing immune dysregulation, shared antigens between the eye and the gut, genetic predisposition, and systemic inflammation driven by high levels of interleukins and cytokines in IBD patients. The complexity of O-EIMs’ pathogenesis reflects in the management of these conditions, varying from topical and systemic steroids to immunomodulatory molecules and biologic therapy, such as anti-tumor necrosis factor (TNF)-alpha. A multidisciplinary approach is the backbone of the management of O-EIMs. Full article

Trabeculectomy has traditionally been upheld as the gold standard in glaucoma surgery, but recent advancements, including the PRESERFLO^® MicroShunt, have introduced less invasive techniques to mitigate complications and reduce intraocular pressure (IOP). The examination of bleb morphology post-filtering surgery is critical for modulating wound healing and ensuring long-term success. While previous evaluations of PRESERFLO-generated blebs have relied on data from trabeculectomy blebs, the differing surgical techniques used in PRESERFLO and trabeculectomy surgeries suggest potential variations in bleb morphologies. This study conducted a comparative analysis of blebs resulting from PRESERFLO and trabeculectomy procedures. Retrospective descriptive assessments using the Jenaer Bleb Grading System were performed, along with quantitative evaluation using eight-dimensional parameters utilizing anterior segment OCT. We included 93 eyes (57 following PRESERFLO, 36 following trabeculectomy). In the descriptive assessment, PRESERFLO-generated blebs exhibited fewer conjunctival cysts (3.5% vs. 22.2%, p = 0.007) and cavernous changes (10.5% vs. 30.5%, p = 0.021) compared to trabeculectomy. Quantitatively, overall bleb dimensions were comparable (maximal bleb height, width, and length, p > 0.05 for all). However, PRESERFLO blebs displayed a shallower (0.52 ± 0.24 vs. 0.67 ± 0.3 mm, p = 0.017) yet longer (4.12 ± 1.54 vs. 3.23 ± 1.64 mm, p = 0.024) episcleral lake. A thicker bleb wall (1.52 ± 0.46 vs. 1.10 ± 0.37 mm, p < 0.001) along with more posteriorly positioned blebs (distance to limbus = 6.16 ± 1.36 vs. 4.87 ± 1.34 mm, p < 0.001) were observed following PRESERFLO. This study illuminates the nuanced morphological differences between PRESERFLO and trabeculectomy blebs. Understanding these distinctions is vital, empowering clinicians to make informed postoperative decisions and avoid misinterpretation of bleb morphology. Full article

Herein, we provide evidence that human regulation of aqueous outflow is by a pump-conduit system similar to that of the lymphatics. Direct observation documents pulsatile aqueous flow into Schlemm’s canal and from the canal into collector channels, intrascleral channels, aqueous veins, and episcleral veins. Pulsatile flow in vessels requires a driving force, a chamber with mobile walls and valves. We demonstrate that the trabecular meshwork acts as a deformable, mobile wall of a chamber: Schlemm’s canal. A tight linkage between the driving force of intraocular pressure and meshwork deformation causes tissue responses in milliseconds. The link provides a sensory-motor baroreceptor-like function, providing maintenance of a homeostatic setpoint. The ocular pulse causes meshwork motion oscillations around the setpoint. We document valves entering and exiting the canal using real-time direct observation with a microscope and multiple additional modalities. Our laboratory-based high-resolution SD-OCT platform quantifies valve lumen opening and closing within milliseconds synchronously with meshwork motion; meshwork tissue stiffens, and movement slows in glaucoma tissue. Our novel PhS-OCT system measures nanometer-level motion synchronous with the ocular pulse in human subjects. Movement decreases in glaucoma patients. Our model is robust because it anchors laboratory studies to direct observation of physical reality in humans with glaucoma. Full article

Elevated intraocular pressure is considered a major cause of glaucomatous retinal neurodegeneration. To facilitate a better understanding of the underlying molecular processes and mechanisms, we report a study focusing on alterations of the retina proteome by induced ocular hypertension in a rat model of the disease. Glaucomatous processes were modeled through sclerosing the aqueous outflow routes of the eyes by hypertonic saline injections into an episcleral vein. Mass spectrometry-based quantitative retina proteomics using a label-free shotgun methodology identified over 200 proteins significantly affected by ocular hypertension. Various facets of glaucomatous pathophysiology were revealed through the organization of the findings into protein interaction networks and by pathway analyses. Concentrating on retinal neurodegeneration as a characteristic process of the disease, elevated intraocular pressure-induced alterations in the expression of selected proteins were verified by targeted proteomics based on nanoflow liquid chromatography coupled with nano-electrospray ionization tandem mass spectrometry using the parallel reaction monitoring method of data acquisition. Acquired raw data are shared through deposition to the ProteomeXchange Consortium (PXD042729), making a retina proteomics dataset on the selected animal model of glaucoma available for the first time. Full article