cFLIP in the molecular regulation of astroglia-driven neuroinflammation in experimental glaucoma.

BACKGROUND: Recent experimental studies of neuroinflammation in glaucoma pointed to cFLIP as a molecular switch for cell fate decisions, mainly regulating cell type-specific caspase-8 functions in cell death and inflammation. This study aimed to determine the importance of cFLIP for regulating astroglia-driven neuroinflammation in experimental glaucoma by analyzing the outcomes of astroglia-targeted transgenic deletion of cFLIP or cFLIPL. METHODS: Glaucoma was modeled by anterior chamber microbead injections to induce ocular hypertension in mouse lines with or without conditional deletion of cFLIP or cFLIPL in astroglia. Morphological analysis of astroglia responses assessed quantitative parameters in retinal whole mounts immunolabeled for GFAP and inflammatory molecules or assayed for TUNEL. The molecular analysis included 36-plexed immunoassays of the retina and optic nerve cytokines and chemokines, NanoString-based profiling of inflammation-related gene expression, and Western blot analysis of selected proteins in freshly isolated samples of astroglia. RESULTS: Immunoassays and immunolabeling of retina and optic nerve tissues presented reduced production of various proinflammatory cytokines, including TNFα, in GFAP/cFLIP and GFAP/cFLIPL relative to controls at 12 weeks of ocular hypertension with no detectable alteration in TUNEL. Besides presenting a similar trend of the proinflammatory versus anti-inflammatory molecules displayed by immunoassays, NanoString-based molecular profiling detected downregulated NF-κB/RelA and upregulated RelB expression of astroglia in ocular hypertensive samples of GFAP/cFLIP compared to ocular hypertensive controls. Analysis of protein expression also revealed decreased phospho-RelA and increased phospho-RelB in parallel with an increase in caspase-8 cleavage products. CONCLUSIONS: A prominent response limiting neuroinflammation in ocular hypertensive eyes with cFLIP-deletion in astroglia values the role of cFLIP in the molecular regulation of glia-driven neuroinflammation during glaucomatous neurodegeneration. The molecular responses accompanying the lessening of neurodegenerative inflammation also seem to maintain astroglia survival despite increased caspase-8 cleavage with cFLIP deletion. A transcriptional autoregulatory response, dampening RelA but boosting RelB for selective expression of NF-κB target genes, might reinforce cell survival in cFLIP-deleted astroglia.

Effect of retrobulbar prostaglandin analog injection on orbital fat in rats.

PURPOSE: Periorbital fat atrophy is a known side effect of topical prostaglandin analogs (PA). This side effect may have implications in the treatment of diseases like thyroid orbitopathy. In this in vivo study we aimed to evaluate the effects of retrobulbar injection of three different PAs on orbital fat. METHODS: Eighteen adult male Wistar-albino rats were divided into three groups of six animals. 0.1 ml of 0.03% bimatoprost, 0.005% latanoprost, or 0.005% travoprost was injected into the right orbits and saline was injected into the left orbits, as controls. Both orbits were exenterated after 3 weeks. Histological cross-sections were analyzed using ImageJ image analysis software. Intraconal adipocyte density was calculated. RESULTS: There was no significant difference in the adipocyte density between the PA injected orbits and the control side in each of the three groups. When calculations from all three groups were analyzed together, again the difference in the adipocyte density between the PA injected orbits and the control side was not significant. CONCLUSION: No significant fat atrophy was noted in this rat model three weeks after retrobulbar injection of PAs. To evaluate retrobulbar injection of PA as a potential therapy for orbital diseases with fat proliferation, in vivo studies in different animal models, higher concentrations of PA, or longer follow-up duration are required.

Retrospective analysis of primarily treated group D retinoblastoma.

PURPOSE: To assess the effectiveness of intra-arterial chemotherapy (IAC), intravenous chemotherapy (IVC), and their combination in the management of group D retinoblastoma. METHODS: This was a retrospective, interventional, comparative, and non-randomized clinical study, including all eyes with primarily treated group D retinoblastoma managed in a single institution from February 2010 to July 2016. Patient demographics, treatment modality (primary enucleation, intravenous chemotherapy, intra-arterial chemotherapy alone or intravenous, and intra-arterial chemotherapy), additional need for consolidation treatments or intravitreal melphalan (IVM) injections, and follow-up time were recorded. The main outcome measure was ocular survival rate after various treatment modalities. RESULTS: Of 87 eyes of 83 consecutive cases, 9 eyes (10.3%) were primarily enucleated, 37 (42.6%) eyes received IVC, 30 (34.5%) eyes had IAC, and 11 (12.6%) eyes were treated with IVC followed by IAC. After a mean 81.1 ± 75.2 weeks of follow-up, enucleation rates were 56.8% in the IVC group, 23.3% in the IAC group, and 36.6% in the IVC + IAC group (p = 0.021). There was no significant difference of ocular survival estimates among these 3 groups at 2 or 5 years (p = 0.998, p = 0.986). With logistic regression analysis, age; gender; disease laterality; administration of IVM, TTT, or cryotherapy; mean dose of IVM; follow-up time; and number of IAC or IVC cycles were not significantly related to the enucleation rate (p > 0.05 for all variables). CONCLUSIONS: Our experience showed that in group D patients, primary IAC achieved ocular survival in 76.7% of eyes, and less need for local consolidation treatments, whereas following primary IVC ocular survival was 43.2%.

Colorimetric Analyses of the Optic Nerve Head and Retina Indicate Increased Blood Flow After Vitrectomy.

Purpose: The purpose of this study was to evaluate the impact of vitrectomy and posterior hyaloid (PH) peeling on color alteration of optic nerve head (ONH) and retina as a surrogate biomarker of induced perfusion changes. Methods: Masked morphometric and colorimetric analyses were conducted on preoperative (<1 month) and postoperative (<18 months) color fundus photographs of 54 patients undergoing vitrectomy, either with (44) or without (10) PH peeling and 31 years of age and gender-matched control eyes. Images were calibrated according to the hue and saturation values of the parapapillary venous blood column. Chromatic spectra of the retinal pigment epithelium and choroid were subtracted to avoid color aberrations. Red, green, and blue (RGB) bit values over the ONH and retina were plotted within the constructed RGB color space to analyze vitrectomy-induced color shift. Vitrectomy-induced parapapillary vein caliber changes were also computed morphometrically. Results: A significant post-vitrectomy red hue shift was noted on the ONH (37.1 degrees ± 10.9 degrees vs. 4.1 degrees ± 17.7 degrees, P < 0.001), which indicates a 2.8-fold increase in blood perfusion compared to control (2.6 ± 1.9 vs. 0.9 ± 1.8, P < 0.001). A significant post-vitrectomy increase in the retinal vein diameter was also noticed (6.8 ± 6.4% vs. 0.1 ± 0.3%, P < 0.001), which was more pronounced with PH peeling (7.9 ± 6.6% vs. 3.1 ± 4.2%, P = 0.002). Conclusions: Vitrectomy and PH peeling increase ONH and retinal blood flow. Colorimetric and morphometric analyses offer valuable insights for future artificial intelligence and deep learning applications in this field. Translational Relevance: The methodology described herein can easily be applied in different clinical settings and may enlighten the beneficial effects of vitrectomy in several retinal vascular diseases.

Automated Category and Trend Analysis of Scientific Articles on Ophthalmology Using Large Language Models: Development and Usability Study.

BACKGROUND: In this paper, we present an automated method for article classification, leveraging the power of large language models (LLMs). OBJECTIVE: The aim of this study is to evaluate the applicability of various LLMs based on textual content of scientific ophthalmology papers. METHODS: We developed a model based on natural language processing techniques, including advanced LLMs, to process and analyze the textual content of scientific papers. Specifically, we used zero-shot learning LLMs and compared Bidirectional and Auto-Regressive Transformers (BART) and its variants with Bidirectional Encoder Representations from Transformers (BERT) and its variants, such as distilBERT, SciBERT, PubmedBERT, and BioBERT. To evaluate the LLMs, we compiled a data set (retinal diseases [RenD] ) of 1000 ocular disease-related articles, which were expertly annotated by a panel of 6 specialists into 19 distinct categories. In addition to the classification of articles, we also performed analysis on different classified groups to find the patterns and trends in the field. RESULTS: The classification results demonstrate the effectiveness of LLMs in categorizing a large number of ophthalmology papers without human intervention. The model achieved a mean accuracy of 0.86 and a mean F1-score of 0.85 based on the RenD data set. CONCLUSIONS: The proposed framework achieves notable improvements in both accuracy and efficiency. Its application in the domain of ophthalmology showcases its potential for knowledge organization and retrieval. We performed a trend analysis that enables researchers and clinicians to easily categorize and retrieve relevant papers, saving time and effort in literature review and information gathering as well as identification of emerging scientific trends within different disciplines. Moreover, the extendibility of the model to other scientific fields broadens its impact in facilitating research and trend analysis across diverse disciplines.

Retinal Hydration Assessment With Optical Coherence Tomography: Unraveling Its Significance in Retinal Fluid Dynamics, Macular Edema and Cell Viability.

Purpose: The purpose of this study was to quantify retinal hydration (RH) levels with optical coherence tomography (OCT) and determine the extent of cellular damage resulting from intraretinal fluid alterations. Methods: We took 6.0 mm sections of the human sensory retina that were excised from 18 fresh (<24 hours) donor eyes. They were either exposed to various osmotic stresses between 90 and 305 mOsm or dehydrated under a laminar flow hood. Change in tissue weight was used to calculate the retinal water content (RWC). Image analyses were conducted on OCT between 0 and 180 minutes to assess retinal thickness (RT) and "optically empty areas" (OEAs) representing intraretinal fluid. Correlations were sought among RWC, OEA, RWC, and RT. The effect of RH on retinal cell viability (RCV) was assessed with the Live-Dead Assay. Results: RH demonstrated a stronger correlation with the OEA than plain RT measurements (r = 0.99, P < 0.001). RH-RCV interaction fits well to a bell-shaped curve. A significant proportion of retinal cells (>80%) remained viable despite the change in RH ranging between 0.87 and 1.42 times. This "safe zone" was found to be associated with a 22% increase in OEA (r = 0.99, P < 0.01). Conclusions: OCT has been demonstrated as a valuable tool for assessing RH and can be used for intraretinal fluid content analysis. RH is a better indicator of RCV compared with RT. Computing RH may improve the determination of functional outcome of intravitreal pharmacotherapeutics used for diabetic macular edema and exudative age-related macular degeneration. Translational Relevance: We link basic research and clinical care by assessing retinal hydration's impact on retinal fluid dynamics, macular edema, and cell viability.

Analysis of the choroidal vascularity in asymmetric pseudoexfoliative glaucoma using optical coherence tomography-based image binarization.

PURPOSE: To analyse choroidal vascular properties using an image binarization tool in patients with asymmetric pseudoexfoliative glaucoma (PXG) and compare them with healthy individuals. METHODS: This cross-sectional study included 144 eyes of 96 patients. The eyes were divided into three groups: 48 glaucomatous eyes and 48 non-glaucomatous contralateral eyes with no clinically observable pseudoexfoliation material of patients with asymmetric PXG, and 48 control eyes. Enhanced depth imaging optical coherence tomography scans of the macula and 3.4-mm diameter, 360-degree circle scans of the optic nerve head were binarized using ImageJ software (National Institutes of Health, Bethesda, MD, USA). The choroidal vascularity index (CVI) was calculated as the ratio of the luminal area to the total circumscribed choroidal area. RESULTS: The macular CVI (mCVI) was significantly lower in the glaucomatous eyes than in the fellow eyes (p = 0.007) and the control eyes (p = 0.001). The peripapillary CVI (pCVI) in all sectors was significantly lower in the glaucomatous eyes than in the other two groups (all p < 0.05). Non-glaucomatous fellow eyes had lower CVI values in the macula and in the peripapillary region, except for the superior-nasal and nasal sectors, compared to the control eyes (all p < 0.05). In multivariate regression analysis, while the cup-to-disc ratio was negatively associated with the pCVI, AL was negatively associated with the mCVI in both eyes of patients with PXG. CONCLUSIONS: CVI was decreased in the macula and peripapillary area in glaucomatous eyes. Furthermore, the CVI tended to decrease in non-glaucomatous fellow eyes of PXG patients. This finding may suggest subclinical involvement and require further exploration into the pathogenesis of glaucoma.

The role of choroidal optical coherence tomography for follow-up of carotid cavernous fistula with anterior drainage.

BACKGROUND: To evaluate the role of the choroidal vascularity index (CVI) and the tortuosity index (TI), along with choroidal thickness measurements, in follow-up for anteriorly draining carotid cavernous fistulas (CCF) that would otherwise necessitate an invasive carotid angiogram. METHODS: In this longitudinal observational study, analysis of enhanced depth imaging spectral domain optical coherence tomography (SD-EDI-OCT) images of 22 patients with angiographically proven unilateral CCF with anterior drainage was performed for subfoveal choroidal thickness (SFCT), central foveal thickness (CFT), CVI and TI. Baseline measurements were compared with those taken at the last visit after occlusion of the fistula. RESULTS: Both in the clinically affected and unaffected eyes, there was a significant decrease in CFT (p = 0.015 and p = 0.005, respectively), SFCT (p = 0.000 for both eyes), CVI (p = 0.002 and 0.001, respectively) and all three TI parameters, including inferior (p < 0.001 and p = 0.01, respectively) and superior temporal vein tortuosity index (p = 0.005 and p = 0.02, respectively) as well as total venular tortuosity index (p < 0.001 and p = 0.002, respectively) after successful closure of the fistula compared to first presentation. Changes in all parameters were similar between the D-CCF and I-CCF groups except for CVI. CONCLUSIONS: In this first study concerning follow-up of anteriorly draining unilateral CCFs by SD-EDI-OCT, we not only demonstrated involvement of the clinically unaffected eye but also showed that, this modality, utilizing CVI and TI together with choroidal thickness measurements, can be used as a readily available, noninvasive first-line followup method for evaluating occlusion of fistulas by endovascular treatment or spontaneous resolution.

Peripapillary and macular choroidal vascularity index in patients with clinically unilateral pseudoexfoliation syndrome.

PURPOSE: To investigate choroidal vascular changes using an image binarization tool in patients with clinically unilateral pseudoexfoliation syndrome (XFS). METHODS: This cross-sectional study included 150 eyes of 100 patients. The eyes were divided into three groups: (1) 50 affected eyes of patients with clinically unilateral XFS; (2) 50 unaffected fellow eyes; and (3) 50 healthy control eyes. Enhanced depth imaging optical coherence tomography scans of the macula and peripapillary regions were acquired. Images were binarized using ImageJ software (National Institutes of Health, Bethesda, MD, USA). The choroidal vascularity index (CVI) was defined as proportion of the luminal area to the total circumscribed choroidal area. RESULTS: Horizontal and vertical scans revealed that the macular CVI values of the affected eyes (60.08 ± 2.06 and 62.21 ± 2.10, respectively) were lower compared with control eyes (67.31 ± 2.24; p = 0.001 and 68.11 ± 2.36; p < 0.001, respectively). Conversely, no significant difference in the macular CVI was found between unaffected fellow and control eyes (p = 0.094 and p = 0.120, respectively). The mean peripapillary CVI values of the temporal (58.73 ± 3.15), superior (59.84 ± 3.09), and inferior (56.94 ± 2.47) sectors were significantly lower in affected eyes compared to control eyes (63.21 ± 3.00, 62.07 ± 3.05, and 60.78 ± 2.88, respectively; p < 0.05 for all). In addition, the unaffected fellow eyes had significantly lower CVI values in the temporal (61.42 ± 3.07) and inferior (57.61 ± 2.56) peripapillary sectors compared with the control eyes (p = 0.007 and p = 0.005, respectively). CONCLUSIONS: These findings suggest that XFS is associated with decreased macular and peripapillary choroidal vascularity. Furthermore, the unaffected eyes of patients with unilateral XFS may show vascularity changes in the peripapillary choroid.

Retinal and Choroidal Optical Coherence Tomography Findings of Carotid Cavernous Fistula.

PURPOSE: To define the retinal and choroidal imaging findings of carotid cavernous fistula (CCF) including central foveal thickness, subfoveal choroidal thickness, choroidal vascularity index (CVI) parameters, and tortuosity indexes (TIs) as compared to a control group (CG). DESIGN: Cross-sectional study. MATERIALS AND METHODS: The spectral domain enhanced-depth imaging optical coherence tomography images of 19 eyes of 19 consecutive patients with angiographically proven CCF and 19 eyes of 19 age- and sex-matched healthy control subjects were included. The patient group was divided according to CCF venous drainage pattern as anterior (A-CCF: draining into ophthalmic veins) and posterior (P-CCF: not draining into ophthalmic veins). The clinically affected eyes of the patient group, ipsilateral to the fistula, were included in the analysis. RESULTS: There were 15 A-CCFs (78.9%) and 4 P-CCFs (21.1%). The mean SFCT of the A-CCF group (395.21 ± 111.69 µm) was significantly higher than those of the P-CCF (246.84 ± 94.12 µm) and CG groups (280.79 ± 111.36 µm) (P = .039 and P = .006, respectively). The mean CVI of the A-CCF group was significantly higher than that of the CG (68.97 ± 4.81 and 65.66 ± 3.37, respectively, P = .033). The A-CCF group had significantly higher inferior, superior, and total venous TI than the CG group (P = .001, P = .001, and P < .001, respectively). CONCLUSION: In this first study investigating the CVI and TI in CCF patients, we demonstrated that SFCT, CVI, and TI could potentially be used to aid in the diagnosis of A-CCF.

Determination of Ophthalmic Drug Proparacaine Using Multi-walled Carbon Nanotube Paste Electrode by Square Wave Stripping Voltammetry.

Proparacaine, one of the most common local anesthetics to facilitate diagnosis and treatment of eye diseases, was assayed by square wave voltammetry using a paste electrode prepared with carbon nanotubes. In cyclic voltammetric studies, proparacaine has exhibited a single irreversible anodic peak at around + 900 mV vs. Ag/AgCl in pH 6.0 Britton-Robinson buffer solution. It was suggested that the peak had appeared due to the oxidation of the NH2 group on the proparacaine molecule. Prior to the determination of the proparacaine by square wave stripping voltammetry (SWSV) on the fabricated multi-walled carbon nanotube paste electrode (MWCNTPE), the accumulation potential (Eacc), accumulation time (tacc), pulse amplitude (ΔE), step potential (ΔEs) and frequency (f ) parameters were optimized. The peak currents plotted in the range of 0.5 - 12.5 mg/L proparacaine exhibited two linear sections with a detection limit of 0.11 mg/L. The results for the determination of proparacaine on a pharmaceutical local anesthetic (Alcaine®) showed that relative standard deviation (RSD) and relative error (RE) were 4.1 and -2.0%, respectively. Selectivity has also been investigated and results showed recoveries of 5.0 mg/L proparacaine in the presence of 5.0 mg/L dopamine, ascorbic acid and uric acid as 106.9 ± 0.8, 99.9 ± 1.2 and 94.1 ± 0.7, respectively.

Is macular pigment optical density really involved in fixation preference?

PURPOSE: To evaluate macular pigment optical density in healthy children and to compare the values with those of strabismic children with respect to fixation preference. METHODS: The study recruited 54 healthy and 41 strabismic children. Two groups were matched in terms of gestational age, birth weight, and body mass index. All participants underwent complete ophthalmological evaluation and macular pigment optical density measurement and filled a self-reported food frequency questionnaire. Strabismic children were categorized according to fixation preference. RESULTS: The mean age was 9.87 ± 2.39 years in healthy children and 9.07 ± 2.07 years in children with strabismus (p = 0.091). Mean macular pigment optical density was 0.23 ± 0.25 in healthy eyes and 0.25 ± 0.27 in non-preferred eyes of strabismic children (p = 0.964). Macular pigment optical density was significantly higher in preferred eyes of strabismic children (0.43 ± 0.34) compared to non-preferred eyes (p = 0.004) and healthy eyes (p = 0.001). There was a difference of macular pigment optical density between both eyes in patients with grades 1, 2, and 3 fixation preference, whereas patients with grade 4 preference had similar macular pigment optical density in both eyes (p = 0.008). There was a statistically significant positive correlation between macular pigment optical density in preferred eyes and body mass index (r = 0.354, p = 0.023). CONCLUSION: Preferred eyes of children with strabismus seem to have higher macular pigment optical density readings. This difference may emerge from the higher tendency of recognizing the flicker stimulus while preferred eye is under testing. Similar macular pigment optical density in healthy and non-preferred eyes and the fact that both lower than preferred eyes remain unexplained. It should be kept in mind that macular pigment optical density results should be carefully interpreted and macular pigment optical density in cases with strabismus should be further investigated.