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1.
Int Ophthalmol ; 44(1): 311, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963456

ABSTRACT

PURPOSE: To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). METHODS: Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. RESULTS: Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49 years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. CONCLUSIONS: Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT.


Subject(s)
Brimonidine Tartrate , Fluorescein Angiography , Glaucoma, Open-Angle , Intraocular Pressure , Macula Lutea , Optic Disk , Retinal Vessels , Tomography, Optical Coherence , Humans , Glaucoma, Open-Angle/physiopathology , Glaucoma, Open-Angle/drug therapy , Glaucoma, Open-Angle/diagnosis , Male , Optic Disk/blood supply , Brimonidine Tartrate/administration & dosage , Brimonidine Tartrate/pharmacology , Brimonidine Tartrate/therapeutic use , Middle Aged , Female , Tomography, Optical Coherence/methods , Macula Lutea/blood supply , Macula Lutea/diagnostic imaging , Intraocular Pressure/physiology , Intraocular Pressure/drug effects , Retinal Vessels/diagnostic imaging , Retinal Vessels/physiopathology , Retinal Vessels/drug effects , Fluorescein Angiography/methods , Regional Blood Flow/physiology , Regional Blood Flow/drug effects , Aged , Fundus Oculi , Prospective Studies , Visual Fields/physiology , Retinal Ganglion Cells/pathology , Retinal Ganglion Cells/drug effects , Antihypertensive Agents/therapeutic use , Nerve Fibers/pathology , Nerve Fibers/drug effects , Adult , Follow-Up Studies
2.
Birth Defects Res ; 116(7): e2384, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38990107

ABSTRACT

BACKGROUND: Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (U.S.). PCG has a autosomal recessive inheritance pattern, and variable expressivity and reduced penetrance have been reported. Likely causal variants in the most commonly mutated gene, CYP1B1, are less prevalent in the U.S., suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the U.S. and to identify novel genes and variants. METHODS: We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention Study (births 1997-2011), a U.S. multicenter study of birth defects. Samples underwent exome sequencing and sequence reads were aligned to the human reference sample (NCBI build 37/hg19). Variant filtration was conducted under de novo and Mendelian inheritance models using GEMINI. RESULTS: Among candidate variants, CYP1B1 was most represented (five trios, 13.5%). Twelve probands (32%) had potentially pathogenic variants in other genes not previously linked to PCG but important in eye development and/or to underlie Mendelian conditions with potential phenotypic overlap (e.g., CRYBB2, RXRA, GLI2). CONCLUSION: Variation in the genes identified in this population-based study may help to further explain the genetics of PCG.


Subject(s)
Cytochrome P-450 CYP1B1 , Exome Sequencing , Exome , Glaucoma , Humans , Glaucoma/genetics , Glaucoma/congenital , Cytochrome P-450 CYP1B1/genetics , Female , Male , Exome Sequencing/methods , United States , Exome/genetics , Mutation/genetics , Genetic Predisposition to Disease , Infant , Infant, Newborn
3.
Article in English | MEDLINE | ID: mdl-38990331

ABSTRACT

BACKGROUND: The focus of therapeutic tools in glaucoma has been mainly to control of intraocular pressure. Recently there has been a growing interest in investigating the relationship of vascular risk factors in the development of glaucoma. The aim of this study was to assess the association between systemic arterial hypertension, diabetes mellitus and hypercholesterolemia, and peripapillary vascularization measured by Optical Coherence Tomography Angiography (OCTA) in glaucoma and healthy subjects. METHODS: In this unicenter, observational, cross-sectional study, 212 subjects, 118 glaucoma patients and 94 controls were consecutively recruited. Of these, 86 participants were excluded due to poor OCTA image quality. Therefore, 146 subjects were included in the final analysis, 74 glaucoma patients and 72 controls. Using a linear regression model, with 95% confidence and 80% statistical power, the effect of vascular risk factors on OCTA parameters in the 146 subjects included in the final analysis was studied. RESULTS: No significant impact of vascular risk factors on OCTA measurements was found. Diabetic patients tended to show a lower peripapillary perfusion vascular density than subjects without diabetes (ß 0.016, 95%CI 0.003;0.030, p 0.016). Similarly, hypercholesterolemia patients appeared to show less peripapillary flow index than non-hypercholesterolaemic patients (ß 0.029, 95%CI 0.013;0.046, p 0.001). Glaucoma patients had 0.02% lower peripapillary perfusion vascular density (ß 0.020, 95% CI 0.011;0.029, p < 0.001), 0.04% lower peripapillary flow index (ß 0.036, 95%CI 0.022;0.051, p < 0.001) and 9.62% thinner retinal nerve fibre layer (ß 9.619, 95%CI 5.495;13.744, p < 0.001). CONCLUSIONS: In conclusion glaucoma has greater effect on peripapillary vascular density parameters than any of the vascular risk factors analyzed. KEY MESSAGES: What is known: • Vascular disfunction plays an important role in the development of glaucoma. • Optical coherence tomography angiography makes it possible to assess the retinal microvasculature and the role that its alterations could have in the development of glaucoma. WHAT IS NEW: • Decrease of the peripapillary microcirculation seems to be more related to the increase in intraocular pressure and the glaucoma itself than to the presence of cardiovascular risk factors. • The effect of having diabetes, systemic arterial hypertension or hypercholesterolaemia on vascular parameters or nerve fibre layer thickness was low. • There was also no relevant impact of the systemic medication used for these diseases on the peripapillary vascular parameters studied or on nerve fibre layer thickness.

4.
Jpn J Ophthalmol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990388

ABSTRACT

PURPOSE: To assess the effectiveness of switching from the concomitant use of brinzolamide 1% (BZM) and brimonidine 0.1% (BMD) to a BZM/BMD fixed-dose combination (BBFC) for the reduction of corneal epithelial damage. STUDY DESIGN: Retrospective cohort study. METHODS: This study involved 52 eyes of 52 glaucoma patients (26 women, 26 men; mean age: 67.0 ± 14.0 years) followed for more than 3 months after being switched from concomitant BZM and BMD to BBFC. Superficial punctate keratitis (SPK) was assessed by fluorescein staining according to the National Eye Institute classification, with the cornea divided into 5 areas: center, superior, nasal, temporal, and inferior. SPK density was graded as 0 (no SPK), 1 (separate SPK), 2 (moderately dense SPK), and 3 (high SPK with overlapping lesions). SPK scores and intraocular pressure (IOP) at pre switching to BBFC (pre-BBFC) and at 3-months post switching to BBFC (post-BBFC) were then compared using the Wilcoxon signed-rank test. RESULTS: At pre-BBFC and post-BBFC, respectively, mean IOP was 12.4 ± 2.5 and 12.4 ± 2.7 mmHg, thus illustrating no significant difference in IOP between pre and post switch (p = 0.924), and the mean SPK score for center, superior, nasal, temporal, and inferior was 0.06 ± 0.24, 0.04 ± 0.19, 0.52 ± 0.67, 0.15 ± 0.36, and 0.92 ± 0.74, and 0.04 ± 0.19, 0.02 ± 0.14, 0.37 ± 0.56, 0.04 ± 0.19, and 0.75 ± 0.62, thus clearly showing a significant reduction in SPK scores for the nasal, temporal, and inferior areas at post-BBFC compared to those at pre-BBFC (p < 0.05). CONCLUSION: Our findings reveal that compared with the concomitant use of BZM and BMD, BBFC is effective in reducing corneal epithelial damage.

5.
Front Ophthalmol (Lausanne) ; 4: 1387190, 2024.
Article in English | MEDLINE | ID: mdl-38984105

ABSTRACT

Overview: This study evaluates the diagnostic accuracy of a multimodal large language model (LLM), ChatGPT-4, in recognizing glaucoma using color fundus photographs (CFPs) with a benchmark dataset and without prior training or fine tuning. Methods: The publicly accessible Retinal Fundus Glaucoma Challenge "REFUGE" dataset was utilized for analyses. The input data consisted of the entire 400 image testing set. The task involved classifying fundus images into either 'Likely Glaucomatous' or 'Likely Non-Glaucomatous'. We constructed a confusion matrix to visualize the results of predictions from ChatGPT-4, focusing on accuracy of binary classifications (glaucoma vs non-glaucoma). Results: ChatGPT-4 demonstrated an accuracy of 90% with a 95% confidence interval (CI) of 87.06%-92.94%. The sensitivity was found to be 50% (95% CI: 34.51%-65.49%), while the specificity was 94.44% (95% CI: 92.08%-96.81%). The precision was recorded at 50% (95% CI: 34.51%-65.49%), and the F1 Score was 0.50. Conclusion: ChatGPT-4 achieved relatively high diagnostic accuracy without prior fine tuning on CFPs. Considering the scarcity of data in specialized medical fields, including ophthalmology, the use of advanced AI techniques, such as LLMs, might require less data for training compared to other forms of AI with potential savings in time and financial resources. It may also pave the way for the development of innovative tools to support specialized medical care, particularly those dependent on multimodal data for diagnosis and follow-up, irrespective of resource constraints.

6.
Front Ophthalmol (Lausanne) ; 4: 1361898, 2024.
Article in English | MEDLINE | ID: mdl-38984121

ABSTRACT

Introduction: While the exchange of a superior valved glaucoma drainage device (GDD) for a non-valved GDD has been reported for achieving glaucoma control, inferior GDD exchange for improving the cosmetic appearance of the eyes due to poor appearance caused by encapsulated GDDs has not been previously documented. Here, we report on two patients with inferior valved GDDs who underwent an exchange for non-valved devices for glaucoma control and cosmetic improvement. Case description: We report on the case of a 23-year-old gentleman and that of an 8-year-old girl, both of whom had inferior valved GDDs with uncontrolled intraocular pressure and unsightly appearance due to encapsulated GDD plates within the palpebral aperture. Both patients were unhappy about the appearance of their eyes. In each case, improvements in both glaucoma control and cosmesis were achieved by exchanging the valved GDDs for non-valved ones. Conclusion: Exchanging a valved for a non-valved GDD might help improve the cosmetic appearance of the eyes, in addition to providing glaucoma control.

7.
Front Ophthalmol (Lausanne) ; 4: 1361704, 2024.
Article in English | MEDLINE | ID: mdl-38984120

ABSTRACT

Corneal transplantation is a common treatment for corneal diseases. Secondary glaucoma after corneal transplantation is the second leading cause of failure of keratoplasty. This article reviews the mechanism and treatment of secondary glaucoma after corneal transplantation.

8.
Front Ophthalmol (Lausanne) ; 4: 1368081, 2024.
Article in English | MEDLINE | ID: mdl-38984126

ABSTRACT

With advancements in the implementation of artificial intelligence (AI) in different ophthalmology disciplines, it continues to have a significant impact on glaucoma diagnosis and screening. This article explores the distinct roles of AI in specialized ophthalmology clinics and general practice, highlighting the critical balance between sensitivity and specificity in diagnostic and screening models. Screening models prioritize sensitivity to detect potential glaucoma cases efficiently, while diagnostic models emphasize specificity to confirm disease with high accuracy. AI applications, primarily using machine learning (ML) and deep learning (DL), have been successful in detecting glaucomatous optic neuropathy from colored fundus photographs and other retinal imaging modalities. Diagnostic models integrate data extracted from various forms of modalities (including tests that assess structural optic nerve damage as well as those evaluating functional damage) to provide a more nuanced, accurate and thorough approach to diagnosing glaucoma. As AI continues to evolve, the collaboration between technology and clinical expertise should focus more on improving specificity of glaucoma diagnostic models to assess ophthalmologists to revolutionize glaucoma diagnosis and improve patients care.

9.
10.
Front Ophthalmol (Lausanne) ; 4: 1294651, 2024.
Article in English | MEDLINE | ID: mdl-38984135

ABSTRACT

Aim: The purpose of this study was to determine the real-world efficacy of early phacoemulsification cataract surgery and goniotomy with a Sinskey hook in patients with glaucoma. Methods: This study was conducted at Advanced Eye Care of New York, a private practice located in Manhattan, NY. This was a single-center, retrospective study of predominantly Black and Afro-Latino patients with glaucoma. These patients underwent early phacoemulsification cataract surgery and goniotomy using an affordable and reusable straight Sinskey hook (Ambler 200-µm tip). Patients who underwent the aforementioned procedure with 6 months of follow-up were included in this study. Investigated parameters were intraocular pressure, number of medications, mean deviation on visual field test, visual acuity, adverse events, and pre/postoperative spherical refractive error. Results: Among all 38 eyes that were enrolled in the study and underwent surgery (goniotomy using a Sinskey hook with phacoemulsification), mean intraocular pressure was reduced from 16.45 mmHg at baseline to 13.24 mmHg at month 6, a 19.5% reduction. The mean number of topical intraocular pressure-lowering medications used was reduced from 1.81 at baseline to 0.52 at month 6, a 71% reduction in topical medications. Conclusion: Combined early cataract surgery and goniotomy performed with a Sinskey hook is an affordable microinvasive surgery and an effective way to reduce intraocular pressure and the number of ocular hypertensive medications used in Black and Afro-Latino patients with primary open-angle glaucoma.

11.
Front Ophthalmol (Lausanne) ; 4: 1385495, 2024.
Article in English | MEDLINE | ID: mdl-38984144

ABSTRACT

Purpose: Blood flow (BF) of the retinal and choroidal vasculatures can be quantitatively imaged using MRI. This study sought to improve methods of data acquisition and analysis for MRI of layer-specific retinal and choroidal BF and then applied this approach to detect reduced ocular BF in a well-established mouse model of glaucoma from both eyes. Methods: Quantitative BF magnetic resonance imaging (MRI) was performed on glaucomatous DBA/2J and normal C57BL/6J mice. Arterial spin labeling MRI was applied to image retinal and choroidal BF using custom-made dual eye coils that could image both eyes during the same scan. Statistics using data from a single eye or two eyes were compared. BF values were calculated using two approaches. The BF rate per quantity of tissue was calculated as commonly done, and the peak BF values of the retinal and choroidal vasculatures were taken. Additionally, the BF rate per retinal surface area was calculated using a new analysis approach to attempt to reduce partial volume and variability by integrating BF over the retinal and choroidal depths. Results: Ocular BF of both eyes could be imaged using the dual coil setup without effecting scan time. Intraocular pressure was significantly elevated in DBA/2J mice compared to C57BL/6J mice (P<0.01). Both retinal and choroidal BF were significantly decreased in DBA/2J mice in comparison to the age-matched normal C57BL/6J mice across all measurements (P < 0.01). From simulations, the values from the integrated BF analysis method had less partial volume effect, and from in vivo scans, this analysis approach also improved power. Conclusion: The dual eye coil setup allows bilateral eye data acquisition, increasing the amount of data acquired without increasing acquisition times in vivo. The reduced ocular BF found using the improved acquisition and analysis approaches replicated the results of previous studies on DBA/2J mice. The ocular hypertensive stress-induced BF reduction found within these mice may represent changes associated with glaucomatous progression.

12.
Curr Dev Nutr ; 8(6): 103789, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38974349

ABSTRACT

Background: Lower density of carotenoids lutein and zeaxanthin (L/Z) in the macula (i.e., macular pigment) has been linked to greater risk for age-related eye disease. Objectives: We evaluated whether macular pigment optical density (MPOD) was associated with manifest primary open-angle glaucoma (POAG) among older women in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2). Methods: MPOD was measured with customized heterochromatic flicker photometry in women who attended CAREDS2 (2016-2019) and CAREDS1 (2001-2004) study visits. Manifest POAG at CAREDS2 was assessed using visual fields, disc photos, optical coherence tomography, and medical records. Age-adjusted linear and logistic regression models were used to investigate the cross-sectional association between POAG and MPOD at CAREDS2, and MPOD measured 15 years earlier at CAREDS1. Results: Among 426 CAREDS2 participants (mean age: 80 y; range: 69-98 y), 26 eyes with manifest POAG from 26 participants were identified. Glaucomatous eyes had 25% lower MPOD compared to nonglaucomatous eyes [mean (SE): 0.40 (0.05) compared with 0.53 (0.01)] optical density units (ODU), respectively (P = 0.01). Compared with MPOD quartile 1, odds for POAG were lower for women in quartiles 2-4 (P-trend = 0.01). After excluding eyes with age-related macular degeneration, associations were similar but not statistically significant (P-trend = 0.16). Results were similar for MPOD measured at CAREDS1. Conclusions: Our results add to growing evidence that low MPOD may be a novel glaucoma risk factor and support further studies to assess the utility of dietary interventions for glaucoma prevention.

13.
Curr Eye Res ; : 1-7, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38979787

ABSTRACT

PURPOSE: We designed a dual-modal fusion network to detect glaucomatous optic neuropathy, which utilized both retinal nerve fiber layer thickness from optical coherence tomography reports and fundus images. METHODS: A total of 327 healthy subjects (410 eyes) and 87 glaucomatous optic neuropathy patients (113 eyes) were included. The retinal nerve fiber layer thickness from optical coherence tomography reports and fundus images were used as predictors in the dual-modal fusion network to diagnose glaucoma. The area under the receiver operation characteristic curve, accuracy, sensitivity, and specificity were measured to compare our method and other approaches. RESULTS: The accuracy of our dual-modal fusion network using both retinal nerve fiber layer thickness from optical coherence tomography reports and fundus images was 0.935 and we achieved a significant larger area under the receiver operation characteristic curve of our method with 0.968 (95% confidence interval, 0.937-0.999). For only using retinal nerve fiber layer thickness, we compared the area under the receiver operation characteristic curves between our network and other three approaches: 0.916 (95% confidence interval, 0.855, 0.977) with our optical coherence tomography Net; 0.841 (95% confidence interval, 0.749, 0.933) with Clock sectors division; 0.862 (95% confidence interval, 0.757, 0.968) with inferior, superior, nasal temporal sectors division and 0.886 (95% confidence interval, 0.815, 0.957) with optic disc sectors division. For only using fundus images, we compared the area under the receiver operation characteristic curves between our network and other two approaches: 0.867 (95% confidence interval: 0.781-0.952) with our Image Net; 0.774 (95% confidence interval: 0.670, 0.878) with ResNet50; 0.747 (95% confidence interval: 0.628, 0.866) with VGG16. CONCLUSION: Our dual-modal fusion network utilizing both retinal nerve fiber layer thickness from optical coherence tomography reports and fundus images can diagnose glaucoma with a much better performance than the current approaches based on optical coherence tomography only or fundus images only.

14.
Curr Eye Res ; : 1-9, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38979820

ABSTRACT

PURPOSE: To investigate the effect of reducing Lysyl oxidase (LOX) overexpression on retinal ganglion cells (RGCs) apoptosis in an acute ocular hypertension (AOH) rat model. METHODS: AOH rat model was performed by anterior chamber perfusion and either received an intravitreal injection with ß-aminopropionitrile (BAPN) or normal saline. After 2wk, Quantification of survival RGCs in the retina was performed using Retrograde FluoroGold labeling. The mRNA expression levels of LOX, LOXL1-4, collagen 1a1 (Col1a1), collagen 3a1 (Col3a1), collagen4a1 (Col4a1), elastin (Eln), fibronectin1 (Fbn1), fibronectin4 (Fbn4) were determined by RT-qPCR. LOX expression was determined by Western blot (WB) analysis and immunohistochemistry. The RNA expression of LOX, Eln and Col1a1 in RGCs retrograde-labeled with 1,1'-dioctadecyl-3,3,3',3' tetra-methylindocarbocyanine perchlorate(DiI)that selected through FACS sorting were determined by RT-qPCR analysis. Changes of the retinal function were detected by Electroretinogram (ERG) analysis. RESULTS: Results showed that significant LOX overexpression and loss of RGCs related to IOP exposure in AOH retinas. PCR analysis indicated significant increased mRNA level of Col1a1, Col3al and Eln in AOH retinas. Significant increase mRNA expression of LOX, Col1a1 and Eln in the RGCs were observed in AOH group compared with CON group. AOH rats injected with BAPN showed a significant decrease in LOX expression, reduced the loss of RGCs and retinal function damage. CONCLUSIONS: The results demonstrated that changes of LOX and specific ECM components in retina were correlated with AOH. Findings from this study indicated that preventing LOX over-expression may be protective against RGCs loss and retinal function damage in AOH animal model.

15.
BMJ Open Ophthalmol ; 9(1)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38960415

ABSTRACT

BACKGROUND: To investigate if there are improvements in trabeculectomy outcomes supporting filtration bleb formation caused by Rho-associated protein kinase (ROCK) inhibitors. METHODS: This prospective, multicentre, randomised, open-label clinical study examined open-angle glaucoma patients who underwent trabeculectomy or trabeculectomy combined with cataract surgery followed by 3-month postoperative ripasudil treatments. After randomly allocating patients to ripasudil-ROCK inhibitor (ripasudil) or without ripasudil (non-ripasudil) groups. Mean intraocular pressure (IOP) changes, success rate, and number of eyedrops were compared for both groups. RESULTS: A total of 17 and 15 subjects dropped out in the ripasudil group and non-ripasudil group, respectively. At baseline, the mean IOP was 16.8±5.0 mm Hg in the ripasudil group (38 patients) and 16.2±4.4 in the non-ripasudil group (52 patients). The IOP decreased to 11.4±3.2 mm Hg, 10.9±3.9 mm Hg and 10.6±3.5 mm Hg at 12, 24 and 36 months in the ripasudil group, while it decreased to 11.2±4.1 mm Hg, 10.5±3.1 mm Hg and 10.9±3.2 mm Hg at 12, 24 and 36 months in the non-ripasudil group, respectively. There was a significant decrease in the number of IOP-lowering medications after trabeculectomy in the ripasudil group versus the non-ripasudil group at 24 (p=0.010) and 36 months (p=0.016). There was no statistically significant difference between the groups for the 3-year cumulative probability of success. CONCLUSION: Although ripasudil application did not increase the primary trabeculectomy success rate, it did reduce IOP-lowering medications after trabeculectomy with mitomycin C.


Subject(s)
Glaucoma, Open-Angle , Intraocular Pressure , Isoquinolines , Mitomycin , Sulfonamides , Trabeculectomy , Humans , Trabeculectomy/methods , Male , Intraocular Pressure/drug effects , Prospective Studies , Female , Glaucoma, Open-Angle/surgery , Glaucoma, Open-Angle/drug therapy , Isoquinolines/therapeutic use , Isoquinolines/administration & dosage , Aged , Sulfonamides/therapeutic use , Sulfonamides/administration & dosage , Mitomycin/therapeutic use , Mitomycin/administration & dosage , Middle Aged , rho-Associated Kinases/antagonists & inhibitors , Treatment Outcome , Alkylating Agents/administration & dosage , Alkylating Agents/therapeutic use
16.
Exp Eye Res ; : 110000, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992852

ABSTRACT

Glaucoma is the leading cause of irreversible blindness worldwide. Previous observational studies have suggested a relationship between central corneal thickness (CCT) and glaucoma; however, the results are inconsistent. This study aimed to investigate whether CCT is associated with a risk for developing open-angle glaucoma (OAG). We employed two-sample Mendelian randomization to assess the relationship between CCT and OAG, namely, primary open-angle glaucoma (POAG) and suspected glaucoma. Genetic instruments composed of variants associated with CCT at genome-wide significance (P <5×10-8) were obtained from published genome-wide association studies from Iglesias et al. for discovery and Bonnemaijer et al. for replication. Summary-level statistics for these instruments for the OAG were obtained from the FinnGen Project (Release 10). Inverse-variance-weighted regression of genetic susceptibility predicted that increased CCT was positively associated with an increased risk for POAG (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.008; P=0.001) and suspected glaucoma (OR, 1.006; 95% CI, 1.003-1.009; P<0.001). In the replication sample of CCT, increased CCT was also positively associated with an increased risk for POAG (OR, 1.004; 95% CI, 1.000-1.008; P=0.029) and suspected glaucoma (OR, 1.005; 95% CI, 1.001-1.008; P=0.013). We found genetic evidence supporting a potential causal association between increased CCT and the risk of POAG and suspected glaucoma in the European population. This findings indicates the clinical significance of CCT in the diagnosis and treatment of glaucoma. Further studies are needed to elucidate the underlying mechanisms of this causal relationship.

17.
Int Ophthalmol ; 44(1): 317, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38972018

ABSTRACT

PURPOSE: To evaluate and compare the long-term outcomes of canaloplasty and phaco-canaloplasty in the treatment of open angle glaucoma and assess the prognostic factors associated with surgical outcome. METHODS: A 48-month retrospective analysis was performed on n = 133 open angle glaucoma eyes treated with canaloplasty and n = 57 open angle glaucoma eyes treated with phaco-canaloplasty by a single surgeon. Surgical success was defined according to six criteria, achieving a target intraocular pressure (IOP) ≤ 21, 18 or 15 mmHg on glaucoma medications (qualified success) or without any further treatment (complete success), including laser therapy or surgery. Kaplan-Meier survival analysis and Cox regression analysis were performed to evaluate surgical success and preoperative factors associated with surgical outcome. Surgical complications in the early postoperative period were compared between canaloplasty and phaco-canaloplasty. RESULTS: Canaloplasty and phaco-canaloplasty significantly reduced postoperative IOP and number of glaucoma medications (p = 0.001 for both). Phaco-canaloplasty showed higher rates of cumulative surgical success over canaloplasty, but only for target IOP ≤ 21 and ≤ 18 (p = 0.018 and p = 0.011, respectively). A preoperative number of > 4 glaucoma medications predicted surgical failure. Phaco-canaloplasty was associated with a higher rate of IOP peaks in the first month compared with canaloplasty (40.4% vs 12.7%, p = 0.000). CONCLUSION: Canaloplasty and phaco-canaloplasty demonstrated long-term efficacy in the treatment of open angle glaucoma, with phaco-canaloplasty showing higher rates of surgical success compared to canaloplasty, but not for target IOPs lower than 16 mmHg. Patients on more than 4 preoperative glaucoma medications may not be good candidates for canaloplasty and may benefit from other surgical options.


Subject(s)
Filtering Surgery , Glaucoma, Open-Angle , Intraocular Pressure , Humans , Glaucoma, Open-Angle/surgery , Glaucoma, Open-Angle/physiopathology , Retrospective Studies , Female , Male , Intraocular Pressure/physiology , Aged , Middle Aged , Filtering Surgery/methods , Follow-Up Studies , Treatment Outcome , Visual Acuity , Phacoemulsification/methods , Aged, 80 and over , Time Factors
18.
Front Ophthalmol (Lausanne) ; 4: 1393555, 2024.
Article in English | MEDLINE | ID: mdl-38984109
20.
Methods Mol Biol ; 2816: 175-191, 2024.
Article in English | MEDLINE | ID: mdl-38977599

ABSTRACT

The trabecular meshwork (TM) from primary open-angle glaucoma (POAG) cases has been found to contain decreased levels of intracellular plasmalogens. Plasmalogens are a subset of lipids involved in diverse cellular processes such as intracellular signaling, membrane asymmetry, and protein regulation. Proper plasmalogen biosynthesis is regulated by rate-limiting enzyme fatty acyl-CoA reductase (Far1). ATPase phospholipid transporting 8B2 (ATP8B2) is a type IV P-type ATPase responsible for the asymmetric distribution of plasmalogens between the intracellular and extracellular leaflets of the plasma membranes. Here we describe the methodology for extraction and culturing of TM cells from corneal tissue and subsequent downregulation of ATP8B2 using siRNA transfection. Further quantification and downstream effects of ATP8B2 gene knockdown will be analyzed utilizing immunoblotting techniques.


Subject(s)
Glaucoma, Open-Angle , Plasmalogens , Trabecular Meshwork , Trabecular Meshwork/metabolism , Trabecular Meshwork/cytology , Humans , Plasmalogens/metabolism , Glaucoma, Open-Angle/metabolism , Glaucoma, Open-Angle/genetics , Glaucoma, Open-Angle/pathology , Adenosine Triphosphatases/metabolism , Adenosine Triphosphatases/genetics , RNA, Small Interfering/genetics , Down-Regulation , Cells, Cultured , Gene Knockdown Techniques
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