CALCIUM CHANNEL BLOCKERS AND GLAUCOMA

 

INTRODUCTION:

Studies have hinted at the possible association of systemic calcium channel blockers (CCB) with the development of glaucoma. In order to analyze this hypothesis a large study was performed using data from the UK Biobank records. The data was analyzed in January 2023 and published in JAMA Ophthalmology.

https://www.ukbiobankeyeconsortium.org.uk/sites/www.ukbiobankeyeconsortium.org.uk/files/89.Calcium%20Channel%20Blocker%20Use%20and%20Associated%20Glaucoma%20and%20Related%20Traits%20Among%20UK%20Biobank%20Participants.pdf

In a cross-sectional study of 427480 adult UK Biobank participants, the study found CCB use was adversely associated with glaucoma prevalence and optical coherence tomography–derived inner retinal thicknesses but not IOP.

Therefore, these drugs may represent an important modifiable risk factor for glaucoma, potentially through an IOP-independent mechanism.

METHODS:

The primary outcome measures included glaucoma status, corneal-compensated IOP, and two OCT-derived inner retinal thickness parameters (macular retinal nerve fiber layer [mRNFL] and macular ganglion cell–inner plexiform layer [mGCIPL] thicknesses). Logistic regression and linear regression analyses were performed to test for associations with glaucoma status and IOP and OCT-derived inner retinal thickness parameters, respectively.

RESULTS:

The median age of participants was 58 (IQR, 50-63) years, and more than half (54.1%) were women.

There were 33 175 CCB users (7.8%).

After adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors, the use of CCBs (but not other antihypertensive agents) was associated with greater odds of glaucoma (odds ratio [OR], 1.39 [95% CI, 1.14 to 1.69]; P = .001).

Calcium channel blocker use was also associated with thinner mGCIPL (−0.34 μm [95% CI, −0.54 to −0.15 μm]; P = .001) and mRNFL (−0.16 μm [95% CI, −0.30 to −0.02 μm]; P = .03) thicknesses but not IOP (−0.01 mm Hg [95% CI, −0.09 to 0.07 mm Hg]; P = .84).

CONCLUSIONS AND RELEVANCE:

In this study, an adverse association between CCB use and glaucoma was observed, with CCB users having, on average, 39% higher odds of glaucoma. Calcium channel blocker use was also associated with thinner mGCIPL and mRNFL thicknesses, providing a structural basis that supports the association with glaucoma. The lack of association of CCB use with IOP suggests that an IOP-independent mechanism of glaucomatous neurodegeneration may be involved.

Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care.

VIALUXE LASER SYSTEM & FLigHT STUDY

 

The ViaLuxe™ Laser System is designed to reduce IOP, using a micron resolution OCT image-guided femtosecond laser, to non-invasively create customized drainage channels through the trabecular meshwork.

https://www.vialase.com/

ViaLuxe Laser System

The machine has the following features =

1. ViaLens Patient Interface:

Non-invasively provides unmatched view and delivery of the femtosecond laser into the trabecular meshwork angle.

2. ViaVue Gonio Camera:

Gonio imaging enables the view of complete structures of the angle in all four quadrants.

3. ViaLuxe Laser:

Precisely creates channels without collateral damage to adjacent tissues.

4. ViaLink:

Bluetooth-connected tablet displays real-time procedure data and diagnostics.

 FLigHT STUDY:

ViaLase, Inc, announced the online publication of 24-month safety data from the first-in-human study of femtosecond laser image-guided high-precision trabeculotomy (FLigHT) performed with the ViaLase technology in Ophthalmology Science, a journal of the American Academy of Ophthalmology.

The investigators in this prospective, non-randomized, single-center, interventional, single-arm trial evaluated 11 patients (17 eyes) with open-angle glaucoma following FLigHT treatment, which consisted of the creation of a single channel through the trabecular meshwork and into Schlemm’s canal. At 24 months post-treatment, the authors reported no device-related serious adverse events and observed well-defined channels with no evidence of closure, indicating medium-term durability.

The study data demonstrated a mean IOP reduction of 34.6% from a baseline of 22.3 ± 5.5 to 14.5 ± 2.6 mmHg at 24 months.

 

JAPAN GLAUCOMA SOCIETY: CLINICAL PRACTICE GUIDELINES FOR GLAUCOMA

 

The Japan Glaucoma Society published the Clinical Practice Guidelines for Glaucoma in 2003, as well as the subsequent revised editions in 2006, 2012, and 2017. The fifth edition has been released in February 2023. 

The guidelines are presented in the following chapters, a short summary of which is being posted here.

https://link.springer.com/article/10.1007/s10384-022-00970-9

Chapter 1: Definition of Glaucoma

Glaucoma is a disease characterized by functional and structural abnormalities of the eye, with characteristic changes in the optic nerve and visual field, wherein optic neuropathy can be alleviated or suppressed by sufficiently lowering intraocular pressure (IOP).

Chapter 2: Classification of Glaucoma

The definition of glaucomatous optic neuropathy (GON) is given as, damage to the optic nerve associated with glaucoma. 

The chapter deals with the classification of glaucomas according to various mechanisms.

Primary open-angle glaucoma (broad) is a disease concept that encompasses both “primary open-angle”, where IOP is higher than the normal range, and “normal-tension glaucoma”. In clinical practice, primary open-angle glaucoma (broad) is divided into high IOP (primary open-angle glaucoma) and normal IOP (normal-tension glaucoma) groups.

Ocular hypertension

Patients with IOP above the statistically defined upper limits of normal; however, without abnormalities in the optic nerve or visual field

Preperimetric glaucoma (PPG)

The term PPG refers to a condition in which there are abnormalities suggestive of glaucoma, such as glaucomatous optic nerve head and retinal nerve fiber defects on ophthalmoscopy and optical coherence tomography (OCT), but no visual field defects are seen on conventional automated static perimetry test.

1. Primary angle-closure glaucoma (PACG):

PACG is a disease in which elevated IOP results from (primary) angle closure induced by genetic background or age-related changes in anterior segment morphology, without other factors, and in which glaucomatous optic neuropathy has already occurred.

2. Primary angle-closure (PAC):

PAC is a condition in which primary angle-closure causes elevated IOP or peripheral anterior synechia (PAS) but does not cause glaucomatous optic neuropathy. The name and etiology of this condition according to the speed of onset are the same as those of PACG.

3. Primary angle-closure suspect (PACS):

PACS is a condition in which there is primary angle-closure but without elevated IOP, organic PAS, or GON. Conversely, only appositional angle closure is present.

Some forms of PACG and PAC develop acutely and are collectively referred to as acute glaucoma attacks. In acute PACG and acute PAC, elevated IOP is often markedly high (40–80 mmHg), and symptoms such as decreased visual acuity, blurring of vision, glaucomatous halo, ocular pain, headache, nausea, vomiting, and diminished or absent light reflexes are common.

Secondary glaucoma is a condition in which elevated IOP is caused by other ocular diseases, systemic diseases, or drug use. Secondary glaucoma is classified according to the mechanism of elevated IOP.

The term childhood glaucoma refers to glaucoma resulting from a condition that develops in childhood. Although the term developmental glaucoma was used in the previous guidelines, the definition and classification have been substantially changed based on the recommendations of the World Glaucoma Association Consensus Conference. However, the upper age limit for childhood glaucoma has not been clearly defined by international standards.

Secondary childhood glaucoma is classified into glaucoma associated with non-acquired ocular anomalies and glaucoma associated with non-acquired systemic disease or syndrome. Those caused by acquired factors such as trauma, steroids, uveitis, and retinopathy of prematurity are classified as glaucoma associated with acquired conditions. Additionally, glaucoma that develops after cataract surgery, which is more frequent among acquired factors, is classified separately as glaucoma following cataract surgery.

Chapter 3: deals with the examination for glaucoma. It consists of the following parts:

i.                    Initial medical interview.

ii.                  Slit-lamp examination.

iii.                Assessment of IOP

iv.                 Gonioscopy

v.                   Fundus examination

vi.                 Visual field analysis

 

Chapter 4: is regarding treatment. It consists of the following parts:

i.                    Principles of glaucoma treatment

ii.                  Treatment practice

 

Chapter 5 is regarding glaucoma drugs.

Chapter 6 informs about laser procedures and their parameters.

Chapter 7 is regarding incisional surgery.

Chapter 8 deals with glaucoma treatment by disease type.

 

NT-501 CNTF IMPLANT

 

Neurotrophic growth factors have been identified as potential therapeutics for neurodegenerative disease. Ciliary neurotrophic factor (CNTF) is one such candidate with strong preclinical evidence for retinal neuroprotection in several animal models that improves the survival and optic nerve axon regeneration of retinal ganglion cells (RGCs). Ciliary neurotrophic factor has been shown to increase retinal thickness in a dose-dependent manner in patients with age-related macular degeneration (AMD) and retinitis pigmentosa.

The NT-501 is a CNTF intraocular implant, being trialed for its role in neuroprotection and neuroenhancement in glaucoma. The implant has been developed by Dr. Jeffrey L. Goldberg, and his team at Stanford University, USA.

NT-501 consists of encapsulated human cells genetically modified (designated as NTC-201) to secrete CNTF.  Cells encapsulated in a semipermeable hollow fiber membrane continuously deliver a low, safe, and therapeutic dose of CNTF into the retina.

The Phase I study involved 11 participants diagnosed with primary open-angle glaucoma (POAG). One eye of each patient was assigned as the study (implant) eye and was implanted with a high-dose CNTF-secreting NT-501 implant, whereas the other eye served as a control. All patients were followed up for 18 months.

Visual acuity and contrast sensitivity decreased more in fellow eyes than in study eyes (VA, −5.82 vs. −0.82 letters; and contrast sensitivity, −1.82 vs. −0.37 letters, for fellow vs. study eyes, respectively). The median HVF visual field index and mean deviation measurements worsened (decreased) in fellow eyes (−13.0%, −3.9 dB) and improved (increased) in study eyes (2.7%, 1.2 dB). Implanted eyes showed an increase in retinal nerve fiber layer thickness measured by OCT and by GDx VCC (OCT, 2.66 μm vs. 10.16 μm; and GDx VCC, 1.58 μm vs. 8.36 μm in fellow vs. study eyes, respectively).

The NT-501 CNTF implant was safe and well tolerated in eyes with POAG. Eyes with the implant demonstrated both structural and functional improvements suggesting biological activity. A foreign-body sensation was the most commonly reported AE and was self-limited to the postoperative period. The most common implant-related AE was pupil miosis; no patients underwent explant.

The Phase II study is currently recruiting and will involve about 30 patients. The patients will be randomized to single implant, double implant, or sham implantation (nothing gets put inside the eye), but the patients are masked to which group they are in. After one year, the patients who were in the sham group will be offered an option to get the real implant.