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Ophthalmology. Glaucoma 2023To examine the generalizability, discuss limitations, and critically appraise recommendations on the management of primary angle-closure suspects (PACSs) that emerged as... (Review)
Review
PURPOSE
To examine the generalizability, discuss limitations, and critically appraise recommendations on the management of primary angle-closure suspects (PACSs) that emerged as a result of recent randomized clinical trials challenging the widely accepted clinical practice of offering laser peripheral iridotomy (LPI) to PACS patients. To synthetize findings from these and other studies.
DESIGN
Narrative review.
SUBJECTS
Patients classified as PACS.
METHODS
The Zhongshan Angle-Closure Prevention (ZAP)-Trial and the Singapore Asymptomatic Narrow Angle Laser Iridotomy Study (ANA-LIS) along with accompanying publications were reviewed. Epidemiologic studies reporting on the prevalence of primary angle-closure glaucoma and other precursor forms of the disease were also analyzed along with publications reporting on the natural course of the disease or studies reporting on outcomes after prophylactic LPI.
MAIN OUTCOME MEASURES
Incidence of progression to more severe forms of angle closure.
RESULTS
Patients recruited in recent randomized clinical trials are asymptomatic, do not have cataracts, may be younger, and have, on average, deeper anterior chambers depth compared with patients treated with LPI in clinics.
CONCLUSIONS
The ZAP-Trial and ANA-LIS clearly represent the best available data on PACS management, additional parameters however may need to be considered when physicians face patients in clinic. PACS patients encountered at tertiary referral centers may represent more advanced cases with respect to ocular biometric parameters and may be at higher risk for disease progression compared with those recruited through population-based screening.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Iris; Intraocular Pressure; Glaucoma, Angle-Closure; Ophthalmologic Surgical Procedures; Lasers
PubMed: 37321374
DOI: 10.1016/j.ogla.2023.06.004 -
Indian Journal of Ophthalmology Mar 2024Selective laser trabeculoplasty (SLT) has experienced a resurgence in interest, primarily driven by promising findings from the Laser in Glaucoma and Ocular Hypertension... (Review)
Review
Selective laser trabeculoplasty (SLT) has experienced a resurgence in interest, primarily driven by promising findings from the Laser in Glaucoma and Ocular Hypertension Trial. By offering SLT as an initial drug-free treatment option, we may be able to thwart issues such as adherence and persistence that plague our current medical management protocols. In this comprehensive narrative review, we delve into the current body of literature that explores the utility of SLT across a wide spectrum of scenarios and glaucoma subtypes. We present evidence that provides valuable insight into the efficacy and benefits of SLT, positioning it as a viable option in the management of glaucoma. Careful consideration of the associated risks and challenges is also necessary for successful adoption into clinical practice. Despite the ample evidence supporting SLT's efficacy, some questions remain regarding its long-term effects and the potential need for retreatment. This review aims to shed light on these aspects to guide clinicians in making informed decisions and tailoring treatment plans to individual patient needs. This review also provides the readers with a bird's eye view of the potential impact of SLT and adds clarity to the various therapeutic protocols that one can follow to ensure optimal clinical outcomes for our patients.
Topics: Humans; Trabeculectomy; Laser Therapy; Glaucoma; Decision Making; Lactic Acid
PubMed: 38421290
DOI: 10.4103/IJO.IJO_2104_23 -
Indian Journal of Ophthalmology Jun 2024Glaucoma, the silent thief of sight, is one of the most common vision-threatening conditions. Even though POAG (primary open angle glaucoma) is more common, PACG... (Review)
Review
BACKGROUND
Glaucoma, the silent thief of sight, is one of the most common vision-threatening conditions. Even though POAG (primary open angle glaucoma) is more common, PACG (primary angle closure glaucoma) is the dreaded variant. ISGEO (International Society for Geographical and Epidemiological Ophthalmology) has classified primary angle closure as PACS (primary angle closure suspect), PAC (primary angle closure), and PACG (primary angle closure glaucoma. The inconspicuous nature of PACS makes its diagnosis and treatment very tricky.
PURPOSE
To determine which cases are best suited for laser peripheral iridotomy.
SYNOPSIS
Laser peripheral iridotomy is the gold standard for acute primary angle closure glaucoma treatment. But there is a lot of confusion regarding its use in PACS as a prophylactic measure. We have tried to throw light on laser peripheral iridotomy, a much debatable topic. The video focuses on various trials regarding laser peripheral iridotomy, the indications, side effects, and contraindications. We have also discussed its use as a therapeutic and prophylactic procedure.
HIGHLIGHTS
The video highlights that the approach of laser peripheral iridotomy should be on a case-by-case basis.
VIDEO LINK
https://youtu.be/kiEYI9ct2Oo.
Topics: Humans; Glaucoma, Angle-Closure; Iridectomy; Intraocular Pressure; Laser Therapy; Iris; Gonioscopy
PubMed: 38804805
DOI: 10.4103/IJO.IJO_1362_23 -
Advances in Therapy Sep 2023This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1%... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.
INTRODUCTION
This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues.
METHODS
A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews.
RESULTS
BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation.
CONCLUSION
As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy.
TRIAL REGISTRATION NUMBER
jRCTs051190125.
Topics: Humans; Timolol; Glaucoma, Open-Angle; Cross-Over Studies; Antihypertensive Agents; Ophthalmic Solutions; Brimonidine Tartrate; Intraocular Pressure; Prostaglandins, Synthetic; Drug Combinations
PubMed: 37452961
DOI: 10.1007/s12325-023-02589-9 -
BMJ Open Aug 2023Glaucoma, a major cause of irreversible blindness, is a highly heritable human disease. Currently, the majority of the risk genes for glaucoma are unknown. We...
PURPOSE
Glaucoma, a major cause of irreversible blindness, is a highly heritable human disease. Currently, the majority of the risk genes for glaucoma are unknown. We established the Genetics of Glaucoma Study (GOGS) to identify disease genes and improve genetic prediction of glaucoma risk and response to treatment.
PARTICIPANTS
More than 5700 participants with glaucoma or a family history of glaucoma were recruited through a media campaign and the Australian Government healthcare service provider, Services Australia, making GOGS one of the largest genetic studies of glaucoma globally. The mean age of the participants was 65.30±9.36 years, and 62% were female. Participants completed a questionnaire obtaining information about their glaucoma-related medical history such as family history, glaucoma status and subtypes, surgical procedures, and prescriptions. The questionnaire also obtained information about other eye and systemic diseases. Approximately 80% of the participants provided a DNA sample and ~70% consented to data linkage to their Australian Government Medicare and Pharmaceutical Benefits Scheme schedules.
FINDINGS TO DATE
4336 GOGS participants reported that an optometrist or ophthalmologist has diagnosed them with glaucoma and 3639 participants reported having a family history of glaucoma. The vast majority of the participants (N=4393) had used at least one glaucoma-related medication; latanoprost was the most commonly prescribed drug (54% of the participants who had a glaucoma prescription). A subset of the participants reported a surgical treatment for glaucoma including a laser surgery in 2008 participants and a non-laser operation in 803 participants. Several comorbid eye and systemic diseases were also observed; the most common reports were ocular hypertension (53% of the participants), cataract (48%), hypertension (40%), nearsightedness (31%), astigmatism (22%), farsightedness (16%), diabetes (12%), sleep apnoea (11%) and migraines (10%).
FUTURE PLANS
GOGS will contribute to the global gene-mapping efforts as one of the largest genetic studies for glaucoma. We will also use GOGS to develop or validate genetic risk prediction models to stratify glaucoma risk, particularly in individuals with a family history of glaucoma, and to predict clinical outcomes (eg, which medication works better for an individual and whether glaucoma surgery is required). GOGS will also help us answer various research questions about genetic overlap and causal relationships between glaucoma and its comorbidities.
Topics: Aged; Humans; Female; Middle Aged; Male; Antihypertensive Agents; Australia; National Health Programs; Glaucoma; Ocular Hypertension; Intraocular Pressure
PubMed: 37536973
DOI: 10.1136/bmjopen-2022-068811 -
Expert Opinion on Investigational Drugs 2023Glaucoma is a leading cause of blindness with intraocular pressure (IOP) as the only known modifiable risk factor. Prostaglandin FP receptor agonists are the first-line... (Review)
Review
INTRODUCTION
Glaucoma is a leading cause of blindness with intraocular pressure (IOP) as the only known modifiable risk factor. Prostaglandin FP receptor agonists are the first-line medical treatment for glaucoma and ocular hypertension. Despite their efficacy, their IOP lowering effect may be insufficient requiring second agents, and poor patient compliance to medical therapy may preclude their full effect.
AREAS COVERED
This literature review examines the novel FP receptor drugs and drug delivery devices in clinical phase trials for treatment of glaucoma. Three novel drugs targeting FP receptors were identified, including latanoprostene bunod, NCX 470, and sepetaprost. Additionally, sustained drug delivery devices in early clinical phase trials included intracameral implants, punctal plugs, ocular rings, and contact lenses.
EXPERT OPINION
NO hybrid FP receptor agonists and dual FP/EP3 receptor agonists may show promise as novel medical therapies with greater efficacy than approved prostaglandin analogs in clinical use, with a similar safety profile. Alternatively, drug delivery systems may provide a similar IOP lowering effect to existing agonists but overcome issues with patient compliance and convenience. A personalized approach to drug delivery devices may be required to ensure the most appropriate fit for the patient according to the invasiveness and duration of therapy desired.
Topics: Humans; Glaucoma; Ocular Hypertension; Receptors, Prostaglandin; Intraocular Pressure; Prostaglandins, Synthetic; Antihypertensive Agents
PubMed: 37929314
DOI: 10.1080/13543784.2023.2279146 -
Investigative Ophthalmology & Visual... Sep 2023Keratin 8/18 (KRT8/18), paired members of the intermediate filament family, have shown vital functions in regulating physiological activities more than supporting the...
PURPOSE
Keratin 8/18 (KRT8/18), paired members of the intermediate filament family, have shown vital functions in regulating physiological activities more than supporting the mechanic strength for cells and organelles. However, the KRT8/18 presence in retinal ganglion cells (RGCs) and functions on neuroprotection in a mouse model of acute ocular hypertension (AOH) are unknown and worthy of exploration.
METHODS
We identified the existence of KRT8/18 in normal human and mouse retinas and primary RGCs. KRT8/18 levels were detected after AOH modeling. The adeno-associated virus (AAV) system was intravitreally used for selective KRT8 knockdown in RGCs. The histological changes, the loss and dysfunction of RGCs, and the gliosis in retinas were detected. The markers of cell apoptosis and MAPK pathways were investigated.
RESULTS
KRT8/18 existed in all retinal layers and was highly expressed in RGCs, and they increased after AOH induction. The KRT8 knockdown in RGCs caused no histopathological changes and RGC loss in retinas without AOH modeling. However, after the KRT8 deficiency, AOH significantly promoted the loss of whole retina and inner retina thickness, the reduction, apoptosis, and dysfunction of RGCs, and the glial activation. Besides, downregulated Bcl-2 and upregulated cleaved-Caspase 3 were found in the AOH retinas with KRT8 knockdown, which may be caused by the increased phosphorylation level of MAPK pathways (JNK, p38, and ERK).
CONCLUSIONS
The KRT8 deficiency promoted RGC apoptosis and neurodegeneration by abnormal activation of MAPK pathways in AOH retinas. Targeting KRT8 may serve as a novel treatment for saving RCGs from glaucomatous injuries.
Topics: Animals; Humans; Mice; Apoptosis; Glaucoma; Ocular Hypertension; Retina; Retinal Ganglion Cells
PubMed: 37656477
DOI: 10.1167/iovs.64.12.1 -
Ophthalmology Jan 2024To review the current published literature for high-quality studies on the use of selective laser trabeculoplasty (SLT) for the treatment of glaucoma. This is an update... (Review)
Review
PURPOSE
To review the current published literature for high-quality studies on the use of selective laser trabeculoplasty (SLT) for the treatment of glaucoma. This is an update of the Ophthalmic Technology Assessment titled, "Laser Trabeculoplasty for Open-Angle Glaucoma," published in November 2011.
METHODS
Literature searches in the PubMed database in March 2020, September 2021, August 2022, and March 2023 yielded 110 articles. The abstracts of these articles were examined to include those written since November 2011 and to exclude reviews and non-English articles. The panel reviewed 47 articles in full text, and 30 were found to fit the inclusion criteria. The panel methodologist assigned a level I rating to 19 studies and a level II rating to 11 studies.
RESULTS
Data in the level I studies support the long-term effectiveness of SLT as primary treatment or as a supplemental therapy to glaucoma medications for patients with open-angle glaucoma. Several level I studies also found that SLT and argon laser trabeculoplasty (ALT) are equivalent in terms of safety and long-term efficacy. Level I evidence indicates that perioperative corticosteroid and nonsteroidal anti-inflammatory drug eye drops do not hinder the intraocular pressure (IOP)-lowering effect of SLT treatment. The impact of these eye drops on lowering IOP differed in various studies. No level I or II studies exist that determine the ideal power settings for SLT.
CONCLUSIONS
Based on level I evidence, SLT is an effective long-term option for the treatment of open-angle glaucoma and is equivalent to ALT. It can be used as either a primary intervention, a replacement for medication, or an additional therapy with glaucoma medications.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Glaucoma; Glaucoma, Open-Angle; Lasers; Ophthalmic Solutions; Ophthalmology; Trabecular Meshwork; Trabeculectomy; United States
PubMed: 37702635
DOI: 10.1016/j.ophtha.2023.07.029 -
Translational Vision Science &... Nov 2023Trabecular meshwork (TM) fibrosis is a crucial pathophysiological process in the development of primary open-angle glaucoma. Pirfenidone (PFD) is a new, broad-spectrum...
PURPOSE
Trabecular meshwork (TM) fibrosis is a crucial pathophysiological process in the development of primary open-angle glaucoma. Pirfenidone (PFD) is a new, broad-spectrum antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis. This study investigated the inhibitory effect of PFD on TM fibrosis and evaluated its efficacy in lowering intraocular pressure (IOP).
METHODS
Human TM cells were isolated, cultured, and characterized. Cell Counting Kit-8 was used to evaluate the proliferation and toxicity of different concentrations of PFD on normal or fibrotic TM cells. TM cells were treated with transforming growth factor beta-2 (TGF-β2) in the absence or presence of PFD. Western blotting and immunofluorescence analyses were used to analyze changes in the TM cell cytoskeleton and extracellular matrix (ECM) proteins, including alpha-smooth muscle actin (α-SMA), F-actin, collagen IV (COL IV), and fibronectin (FN). An ocular hypertension (OHT) mouse model was induced with Ad-TGF-β2C226/228S and then treated with PFD or latanoprost (LT) eye drops to confirm the efficacy of PFD in lowering IOP.
RESULTS
PFD inhibited the proliferation of fibrotic TM cells in a dose-dependent manner and inhibited TGF-β2-induced overexpression of α-SMA, COL IV, and FN in TM cells. PFD stabilized F-actin. In vivo, PFD eye drops reduced the IOP of the OHT models and showed no significant difference compared with LT eye drops.
CONCLUSIONS
PFD inhibited TGF-β2-induced TM cell fibrosis by rearranging the disordered cytoskeleton and decreasing ECM deposition, thereby enhancing the aqueous outflow from the TM outflow pathway and lowering IOP, which provides a potential new approach to treating glaucoma.
TRANSLATIONAL RELEVANCE
Our work with pirfenidone provides a new approach to treat glaucoma.
Topics: Animals; Humans; Mice; Actins; Cells, Cultured; Fibrosis; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Ophthalmic Solutions; Trabecular Meshwork; Transforming Growth Factor beta2
PubMed: 37975842
DOI: 10.1167/tvst.12.11.21 -
International Ophthalmology Oct 2023To investigate the ocular surface inflammation in patients with primary open angle glaucoma and ocular hypertension by analyzing tears and to compare findings with... (Observational Study)
Observational Study
PURPOSE
To investigate the ocular surface inflammation in patients with primary open angle glaucoma and ocular hypertension by analyzing tears and to compare findings with healthy controls.
METHODS
Observational case-control study. Tear samples were collected by 5 µl microcapillary tube from 24 patients with glaucoma treated by antiglaucoma drops, 9 non-treated patients with ocular hypertension and 45 healthy controls. Tears were analyzed from right eye by multiplex Bio-Plex system for the presence of 6 cytokines: IL1β, IL10, IL4, IFNγ, MIF and VEGF.
RESULTS
Significantly higher concentrations of IL1β and IL10 (glaucoma or ocular hypertension vs. healthy controls, p < 0.0001), VEGF (glaucoma vs. ocular hypertension, p < 0.05; ocular hypertension vs. healthy controls, p < 0.02) and MIF (glaucoma vs. healthy controls, p < 0.03) were detected in patients' tears. Both patient groups have activated to a significantly lower extent the Th1 pathway represented by IFNγ than Th2 pathway represented by IL10 (p < 0.001) and, at the same time, the IFNγ/IL4 ratio was significantly increased in healthy controls (p < 0.001) and patients with ocular hypertension (p < 0.02) compared to glaucoma individuals.
CONCLUSION
This study shows that secretion of inflammation-related cytokines by conjunctival cells is increased in both, glaucoma and ocular hypertension patients and can be detected in their tears. Nevertheless, data indicates stronger ocular surface inflammation in non-treated follow-up patients diagnosed with ocular hypertension than in glaucoma subjects treated by antiglaucoma drops.
Topics: Humans; Cytokines; Glaucoma, Open-Angle; Case-Control Studies; Interleukin-10; Interleukin-4; Vascular Endothelial Growth Factor A; Intraocular Pressure; Glaucoma; Ocular Hypertension; Tears; Inflammation; Antihypertensive Agents; Ophthalmic Solutions
PubMed: 37318666
DOI: 10.1007/s10792-023-02763-6