Proteomics reveals a set of highly enriched proteins in epiretinal membrane compared with inner limiting membrane.

Few data exist regarding the protein composition of idiopathic epiretinal membrane (iERM). In the present study we compared the proteome of epiretinal membrane of iERM with the proteome of the inner limiting membrane (ILM) of idiopathic macular hole (iMH). Twelve epiretinal membrane samples were obtained from patients with iERM undergoing therapeutic vitrectomy. Twelve ILM samples from patients with iMH were used as controls. Proteomic analysis was conducted with discovery-based label-free quantitative nano-liquid chromatography - tandem mass spectrometry (LFQ nLC-MS/MS). Verification of results was performed with targeted MS using selected reaction monitoring on a different set of samples. Discovery data were searched against the Uniprot Homo sapiens protein database using MaxQuant Software. Identified proteins were filtered with Perseus software. Bioinformatic analysis of the differences in protein expression between epiretinal membrane from iERM and ILM from iMH was performed using STRING. A total of 2,183 different proteins were identified. 357 proteins were found to be present in all samples. The protein profile of iERM was highly different from iMH with 62 proteins found at significantly higher levels in iERM. The proteins upregulated more than 10-fold in iERM were: fibrillin-1, tenascin, prolargin, biglycan, opticin, collagen alpha-1(II) chain, protein-glutamine gamma-glutamyltransferase 2, fibronectin, filamin-A, collagen alpha-2(IX) chain, spectrin alpha chain, transforming growth factor beta induced protein ig-h3, dihydropyrimidinase - related protein 3, endoplasmin and glutamate dehydrogenase 1. Proteins with high level in iERM consisted of proteins that especially localized to the actin cytoskeleton, the extracellular matrix and the mitochondrion. Analysis of all proteins indicated that the disease process in iERM at least in part can be characterized as skin formation with perturbation of nucleotide metabolism. Our study identified proteins that have not earlier been associated with iERM. Fifteen proteins are found at very high concentration, 10-fold or more, and amongst these four proteins, fibrillin-1, tenascin, prolargin and biglycan were found at more than a 100-fold higher content compared to ILM of iMH. These proteins may be potential therapeutic targets. Data are available via ProteomeXchange with identifier PXD014286.

Multilayered pigment epithelial detachment in neovascular age-related macular degeneration.

PURPOSE: To describe the spectral domain optical coherence tomography findings in eyes with chronic fibrovascular pigment epithelial detachment (PED) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: Retrospective observational case series of patients with chronic fibrovascular PEDs receiving serial intravitreal anti-VEGF therapy. Corresponding spectral domain optical coherence tomography scans of chronic PEDs were studied in detail over multiple visits. The internal structure within the sub-PED compartment was analyzed, characteristic features were identified, and then correlated with visual outcome. RESULTS: Thirty-eight eyes of 34 patients with fibrovascular PEDs were included. Mean and median Snellen visual acuity was 20/50 (range, 20/20-20/400). Eyes received a mean of 28.2 intravitreal anti-VEGF injections (median, 23.0; range, 3-70) administered over a mean of 36.9 months (median, 37.5; range, 6-84). A fusiform, or spindle-shaped, complex of highly organized layered hyperreflective bands was noted within each PED. Nineteen eyes demonstrated heterogenous, dilated, irregular neovascular tissue adherent to the undersurface of the retinal pigment epithelium. Additionally, 25 eyes demonstrated a hyporeflective cavity separating the choroidal neovascularization complex from the underlying choroid. CONCLUSION: Chronic fibrovascular PEDs receiving serial anti-VEGF therapy demonstrate a characteristic fusiform complex of highly organized, layered, hyperreflective bands, termed a "multilayered PED," which is often seen in conjunction with neovascular tissue adherent to the undersurface of the retinal pigment epithelium monolayer. On the basis of previous histopathologic correlations, these bands may represent a fibrous tissue complex with contractile properties. An associated hyporeflective space, termed a "pre-choroidal cleft," separates the fusiform complex from the underlying choroid and may be due to contraction, the exudation of fluid, or both. Many of these eyes maintain good visual acuity, presumably because the neovascular and cicatricial process is suppressed within the sub-retinal pigment epithelium space by chronic anti-VEGF therapy, thus permitting the viability of the photoreceptor population through preservation of the retinal pigment epithelium.

Nodular hidradenoma of the caruncle.

An 84-year-old man presented with a tumor of the right caruncle causing epiphora due to insufficient eyelid closure. The tumor was cystic and mucinous in appearance. MRI showed a solitary tumor of the caruncle with no adhesions to neighboring tissue. The mass was removed by carunculectomy. Histopathologic examination revealed a tumor composed of epithelial cells with intervening strands of hyalinized stroma. Solid areas were predominant but a cribriform area could also be distinguished. Periodic acid-Schiff positive, diastase-labile material (glycogen) was detected in many tumor cells. Immunohistochemical staining of the tumor cells demonstrated positive staining with antibodies against CK-CAM 5.2, BER-EP4, p63, and smooth muscle actin-positive cells in some areas. The tumor was diagnosed as a nodular hidradenoma of the caruncle, which has never been reported before and should be included in the diagnoses of caruncular tumors.

Multimodal Retinal Imaging of Intravascular Lipid in Severe/Extreme Hypertriglyceridemia.

Retinal intravascular lipid aggregates were detected in the left eye in a patient with uncontrolled diabetes and very high blood triglycerides. The patient suffered visual loss in the left eye due to retinal ischemia. Optical coherence tomography, fluorescein angiography, infrared fundus photography, and autofluorescence studies of the retina demonstrated unique findings. Slowed choroidal and retinal flow was detected on fluorescein angiography, and a prominent middle layer membrane sign was present on OCT. Intravascular lipid reflectivity was manifest on retinal infrared and autofluorescence imaging. Eventually, insulin and statin therapy proved effective in reversing the vascular lesions, although retinal atrophy finally ensued. This report of a very rare clinical condition provides unique findings on multimodal retinal imaging and confirms the need for prompt insulin and statin therapy in severe/extreme hypertriglyceridemia and dysregulated diabetes. One similar case was reported in the past when multimodal imaging studies of the retina were not available. The lesions described herein should be differentiated from the more frequently encountered lipemia retinalis as they may confer worse prognosis.

Endophthalmitis after intravesical bacillus Calmette-Guérin therapy for bladder cancer.

Intravesical instillation of bacillus Calmette-Guérin (BCG) is used for the maintenance treatment of some types of bladder cancer. Although rare, ocular complications can develop following intravesical BCG treatment. This is a case report of culture-positive Mycobacterium bovis BCG endophthalmitis following intravesical BCG installation. The case highlights a rare complication of BCG installation and the need for an eye examination when patients after BCG installation develop eye symptoms.

Outbreak of Bilateral Endophthalmitis After Immediate Sequential Bilateral Cataract Surgery.

Importance: Since bilateral simultaneous postoperative endophthalmitis (BSPOE) after immediate sequential bilateral cataract surgery (ISBCS) can be devastating for the patient, evaluating such cases in depth is important to maintaining patient safety. Objective: To evaluate whether a systemic breach of sterility was associated with an outbreak of BSPOE after ISBCSs performed on the same day at a single community-based eye clinic. Design, Setting, and Participants: This retrospective case series included all patients diagnosed with BSPOE at ophthalmology departments in Denmark following an infectious outbreak after ISBCSs performed at a single community-based eye clinic in December 2022. Exposure: Bilateral simultaneous postoperative endophthalmitis acquired after ISBCS. Main Outcome and Measures: Patient recovery from BSPOE after ISBCS was evaluated based on clinical and microbiological reports. Results: A woman aged 71 years, a man aged 84 years, and a woman aged 79 years consecutively presented with symptoms of endophthalmitis at regional eye departments 4 to 8 days after ISBCS performed on the same date at the same eye clinic. Five of 6 infected eyes underwent vitrectomy, and all eyes received an intravitreous injection of antibiotics. The same strain of Staphylococcus epidermidis was isolated in 4 of 5 eyes that underwent vitrectomy. Contamination of viscoelastics was ruled out with repeated cultures. One eye was eviscerated due to phthisis. In another patient, the final visual acuity of the eye most severely affected was 20/63 Snellen equivalents. Visual acuity of the remaining eyes recovered to 20/25 (3 eyes in 2 patients) and 20/20 (1 eye) Snellen equivalents. Conclusions and Relevance: The finding of the same strain of S epidermidis in all patient cultures suggests a systemic breach of sterility at the clinic on the day of ISBCS. The outcome of these cases emphasizes the need to adhere to a strict surgical methodology and sterile principles during ISBCS.

The role of cytokines and hot flashes in perimenopausal depression.

BACKGROUND: An imbalance in the production of proinflammatory and anti-inflammatory cytokines may play a role in the pathophysiology of perimenopausal depression. The aim of this study was to examine serum levels of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNFα), and the anti-inflammatory cytokine IL-10, in perimenopausal women suffering from depression. Furthermore, to assess whether serum cytokine levels are associated with the presence of hot flashes or the use of selective serotonin reuptake inhibitors (SSRIs). We also evaluated the possible association of hot flashes and perimenopausal depression. METHODS: Serum samples from 65 perimenopausal women, 41 with depression and 24 without depression, were assessed for serum IL-6, TNFα and IL-10 by conventional enzyme-linked immunosorbent assays. Depression was evaluated by the 17-item Hamilton Depression Rating Scale (HAM-D 17) and a psychiatric interview. The presence and severity of hot flashes were examined using the Menopause Rating Scale (MRS). RESULTS: Serum levels cytokines did not differ between depressed women and normal controls. Serum levels of cytokines did not change significantly in depressed women with hot flashes or in depressed women treated with SSRIs. Hot flashes were strongly associated (P < 0.0001) with perimenopausal depression. CONCLUSION: The study supports the hypothesis that perimenopausal depression is not characterized by increased proinflammatory cytokines and decreased anti-inflammatory cytokines. Women with perimenopausal depression suffer from more severe and more frequent hot flashes than women without perimenopausal depression.

A comparative study of strabismus surgery with retained or removed scleral explant after retinal detachment surgery.

PURPOSE: To compare, in a larger study population, the outcomes of strabismus surgery in patients who either had the scleral explant (EX) retained or removed after surgery for retinal detachment. METHODS: A comparative retrospective study includes data from 2 centres. Surgical outcome, motor success, sensory success, the number of secondary operations for strabismus and complications were compared between the two groups. Motor success was defined as horizontal deviation of ≤6 prism diopters (PD) and vertical deviation of ≤6PD. Sensory success was defined as no diplopia without use of prism. RESULTS: Forty-seven patients were included in the study; 70% had retained the EX and 74% had vertical strabismus. Horizontally, the final alignment was equal between the 2 groups, 4 PD vs.5 PD in the EX removed group. The patients with retained EX were referred with a significant lower mean vertical deviation and had a significant lower post-operative mean vertical deviation of 2 PD vs. 3 PD in the EX-removed group. The rates of motor success (76% vs. 71%) and sensory success (79% vs. 93%) did not differ significantly between the EX-retained and EX-removed groups. No patients underwent more than 2 operations. Two complications occurred in the EX-retained group: a subconjunctival cyst and an exposed EX. In the EX-removed group, 2 patients with retinal re-detachment were found in the follow-up period. CONCLUSION: Good surgical outcomes including high motor and sensory success were obtained regardless of the presence of the EX. Retinal re-detachment was observed in two patients with previously removed EX.

[Protein kinase inhibitors can induce retinopathy].

Novel treatment strategies such as targeted therapy with mitogen-activated protein-kinase-kinase/B-Raf proto-oncogene (MEK/BRAF) inhibitors have prolonged patient survival in metastatic melanoma and are used in oncology. The combination of binimetinib og encorafenib can induce extensive bilateral neuroretinal detachments. In this case report, we present a 72-year-old female patient with this condition. Dilated fundus examination and optical coherence tomography are essential in diagnosis and monitoring of patients treated with MEK/BRAF-inhibitors. No persistent visual deficits were documented in the patient, as this condition appears to be fully reversible.

Development and validation of a multiple-choice questionnaire-based theoretical test in direct ophthalmoscopy.

PURPOSE: Direct ophthalmoscopy can reveal systemic, neurologic and ophthalmic conditions, but is poorly mastered among young physicians. A theoretical test is needed to measure effect of educational interventions. We developed and gathered validity evidence for a multiple-choice questionnaire (MCQ)-based theoretical test in direct ophthalmoscopy. METHODS: The MCQ was developed by interviewing experts. Then, validity evidence was evaluated using Messick's validity framework. Content was ensured by inviting the experts to contribute in a Delphi-like process. Response process was ensured by piloting and by streamlining all instructions. Then, the test was taken by ophthalmologists and by medical students without experience in direct ophthalmoscopy. Results were used to evaluate internal structure (item quality analysis and internal consistency), relations to other variables (correlation of test scores to experience level) and consequences (establishment of pass-fail score and the consequences of its use). RESULTS: The first phase of the study yielded 100 MCQs. In second phase, we identified that 60 items fulfilled predefined relevance and item quality requirements. These items demonstrated very high internal consistency (Cronbach's alpha = 0.95), significantly discriminated medical students from specialists (p < 0.001, independent samples t-test) and the established pass-fail score of 50 (83%) correct answers resulted in no false positives (students passing) and no false negatives (specialists failing). A Decision study identified that sampling 15 items suffice for certification. CONCLUSION: We developed and validated an MCQ-based theoretical test in direct ophthalmoscopy that enables an evidence-based approach to measuring, evaluating and certifying the theoretical knowledge necessary for direct ophthalmoscopy.

[Parinaud syndrome caused by corpus pineale tumour in a 14-year-old boy].

Parinaud syndrome (PS) can manifest in a pineal tumour. Major components of PS include restriction of gazing upwards, light-near dissociation and convergence retraction nystagmus. A 14-year-old boy presented with diplopia and restricted ability to gaze upwards. The objective examination revealed signs, which were compatible with the major manifestations of PS. A magnetic resonance scan (MRI) of cerebrum indicated pinealoma, and a pathological examination identified the lesion as a germ cell carcinoma. The patient received chemotherapy and stereotactic radiosurgery. The ophthalmic symptoms improved, and a follow-up MRI demonstrated complete regression of the tumour.

[Parinaud syndrome caused by corpus pineale tumour in a 14-year-old boy].

Parinaud syndrome (PS) can manifest in a pineal tumour. Major components of PS include restriction of gazing upwards, light-near dissociation and convergence retraction nystagmus. A 14-year-old boy presented with diplopia and restricted ability to gaze upwards. The objective examination revealed signs, which were compatible with the major manifestations of PS. A magnetic resonance scan (MRI) of cerebrum indicated pinealoma, and a pathological examination identified the lesion as a germ cell carcinoma. The patient received chemotherapy and stereotactic radiosurgery. The ophthalmic symptoms improved, and a follow-up MRI demonstrated complete regression of the tumour.

An OCT Study of Anterior Nodular Episcleritis and Scleritis.

Anterior scleritis and episcleritis are a well-known presentation in tuberculosis. The case of a female patient with presumed tuberculous anterior scleritis and episcleritis is discussed in this article. Anterior segment OCT was efficient in diagnosis and evaluation of the therapeutic outcome. Antituberculosis chemotherapy was sufficient to achieve clinical remission.