EYEDROP AIDS

 

Glaucoma is usually seen in elderly individuals. Due to age, other comorbidities, and lack of social support, glaucoma patients have difficulties in instilling the eyedrops prescribed for their disease. Lack of compliance is a significant factor in poor control of intraocular pressure (IOP).

In order to overcome the difficulty in drop instillation, eye drops aids have been devised. Eye drop aids are small, reusable tools that attach to standard medication bottles to ensure accurate alignment, prevent blinking, and make squeezing easier. They reduce drop waste and minimize the risk of touching the eye's surface with the bottle tip.

A few types of eyedrop aids are presented here:

AUTODROP:

Autodrop is a mechanical device designed to facilitate precise eye drop delivery. It attaches to standard eye drop bottles and rests on the cheek bone, ensuring proper alignment and minimizing spillage outside the eye.

Advantages:

• User friendly
• Offers improved accuracy in eye drop delivery
• Ease of use
• Decreased risk of bottle tip contamination
• Decreased risk of injury to the eye surface from the bottle tip

Disadvantages:

• The inconvenience of an additional step.
• May increase the number of drops used for some patients.

AUTOSQUEEZE:

Autosqueeze & Opticare Arthro: These are lever-based attachments designed to increase gripping leverage, making it much easier to squeeze bottles if you have arthritis or grip issues. Autosqueeze is a mechanical device designed to eliminate the difficulty of squeezing the eyedrop bottle. It has a central holder that attaches to standard eye drop bottles and a wing on either side. Squeezing the wings will cause the grooves on the inside of the wing to apply pressure to the eye drop bottle so that one eye drop is released.

Advantages:

• Ergonomic grip
• Helps overcome mobility difficulties
• Can be used in combination with the Autodrop

Disadvantages:

• Inconvenience of an additional step.

NANODROPPER:

Nanodropper is a portable attachment that reduces the size of eye drop droplets, allowing for more efficient dosing and reduced wastage. It attaches to standard eye drop bottles and dispenses smaller, more precise drops, maximizing the number of doses per bottle.

Advantages:

• Precision dosing
• Improved adherence to the medication schedule
• Cost efficiency
• Decreased side effects
• Decreased waste
• Improved accuracy

Disadvantages:

• Learning curve to using the device
• Inconvenience of an additional step
• Extending the bottle life span may increase the risk for contamination
• Its compatibility with different bottle designs may vary.

GENTLEDROP:

GentleDrop is a nose point pivot device, where the eye drop bottle is inserted into a sleeve. That sleeve is then rested on the bridge of the nose, ensuring proper alignment.

Advantages:

• Improved aim
• Minimizing waste
• Reduced risk of bottle tip contamination

Disadvantages:

• Incompatible with some eye drop bottles
• Inconvenience of an additional step
• May be difficult to use for patients with limited dexterity.

EYE DROP GUIDE:

The Eyedrop Guide ensures precise application of eye drops, making it easier for both seniors and children to use. This eyedrop guide aid is compact making it convenient to carry in a bag or pocket for on the go use.

This eyedrop bottle dispenser avoids waste caused by incorrect and extra instillation of drops. This eye dropper aid tool is made of abs material, making it easy to clean and reusable.

All these devices ensure proper application of eyedrops and decrease the efforts required for eyedrop delivery, ensuring maximal compliance.

Amazon link:

https://www.amazon.in/GentleDrop-Reusable-Silicone-Accessory-Dispenser/dp/B0BQBHRKV1

THERMORESPONSIVE GELS

 

Thermoresponsive gels are typically composed of polymers that exhibit a lower critical solution temperature (LCST). Below this temperature, the polymer exists as a liquid (sol), allowing for easy administration. Upon exposure to physiological temperatures (approximately 37°C), the polymer undergoes a phase transition to form a gel, which can act as a reservoir for sustained drug release.

Mechanism of Action: Sol-Gel Transition:

The sol-gel transition in thermoresponsive gels is driven by changes in the polymer's hydrophilic-hydrophobic balance as the temperature increases. Below the LCST, the polymer chains are hydrated and remain in solution. As the temperature rises above the LCST, the polymer undergoes dehydration, leading to chain collapse and gel formation. This gelation process is reversible, meaning that the gel can return to a sol state if the temperature drops below the LCST. However, in the context of ocular drug delivery, the temperature remains relatively constant, ensuring that the gel remains in place for an extended period.

Advantages in Overcoming Ocular Barriers:

The eye's anatomy presents several barriers to effective drug delivery, including the corneal epithelium, tear film, and conjunctival clearance mechanisms. Thermoresponsive in situ gels offer several advantages in overcoming these barriers:

1. Enhanced Corneal Penetration: The prolonged contact time provided by the gel allows for greater drug absorption across the cornea, increasing the bioavailability of the drug.
2. Reduction of Precorneal Drug Elimination: The gel's viscosity helps to retain the drug on the ocular surface, reducing the rate of drug elimination by tear turnover and blinking.
3. Improved Retention in the Conjunctival Sac: The gel formation in the conjunctival sac prevents rapid drainage of the drug, ensuring that it remains in contact with the ocular surface for a longer period.

These advantages make thermoresponsive in situ gels an attractive option for delivering drugs to the eye, particularly for conditions like glaucoma, where sustained drug delivery is critical for maintaining IOP control.

Applications of Thermoresponsive In Situ Gels in Glaucoma Treatment:

The utilization of thermoresponsive in situ gels for glaucoma treatment offers promising opportunities to address the challenges of sustained drug delivery, improved patient compliance, and enhanced therapeutic efficacy.

Anti-Glaucoma Drugs Formulated in Thermoresponsive Gels:

Several anti-glaucoma drugs have been incorporated into thermoresponsive in situ gel formulations to improve their efficacy and patient adherence. These drugs are primarily aimed at lowering IOP, which is a key modifiable risk factor in glaucoma management. The most commonly used drugs in such formulations include: Prostaglandin analogs, beta blockers, alpha agonists, carbonic anhydrase inhibitors and combination therapies.

Clinical Benefits of Thermoresponsive Gels in Glaucoma:

Thermoresponsive in situ gels offer several clinical benefits in the treatment of glaucoma, especially in terms of improving therapeutic outcomes, patient compliance, and minimizing adverse effects:

1. Sustained IOP Control: One of the primary advantages of thermoresponsive gels is their ability to maintain therapeutic drug levels over extended periods. This sustained release results in more consistent IOP control, reducing fluctuations that can occur with traditional eye drop therapies.
2. Reduced Dosing Frequency: By prolonging the retention time of drugs on the ocular surface, thermoresponsive gels decrease the frequency of administration. Patients who previously required daily or multiple daily doses of medication can potentially achieve adequate IOP control with weekly or biweekly applications. This reduction in dosing frequency is particularly beneficial for elderly patients or those with cognitive or physical limitations.
3. Improved Bioavailability: The gel's ability to remain on the ocular surface for an extended period enhances the penetration of the drug through the cornea, improving its bioavailability and efficacy. This is especially important for drugs that have poor corneal penetration in conventional formulations.
4. Minimized Systemic Absorption: The increased retention of the drug in the eye reduces the risk of systemic absorption and associated side effects, such as cardiovascular or respiratory effects seen with beta-blockers or other medications.
5. Enhanced Patient Compliance: The ease of administration and reduced dosing frequency contribute to better patient compliance, which is critical in managing a chronic disease like glaucoma. Studies have shown that patients are more likely to adhere to simpler treatment regimens, which can ultimately improve clinical outcomes.

REFERENCE:

Maroof M, Pandey AA. Thermo-responsive in-situ gel for ocular glaucoma: A comprehensive review. International Journal of All Research Education and Scientific Methods (IJARESM), ISSN: 2455-6211, Volume 12, Issue 8, August-2024.

DANDELION AND GLAUCOMA

 

Erigeron breviscapus (EB), also known as Dandelion Flower, is the dried whole herb of the Asteraceae plant.

Studies have shown that EB has the effects of dilating blood vessels, improving microcirculation, increasing blood flow, expanding the visual field, and protecting retinal ganglion cell damage in rats caused by elevated intraocular pressure.

A study was conducted using "Network Pharmacology" to elucidate the mechanism of action of EB in the treatment of glaucoma.

Network pharmacology is a branch of science that, based on the theoretical foundations of systems biology and multidirectional pharmacology, utilizes biomolecular network analysis methods to examine the effective components and their synergistic effects in Traditional Chinese Medicine (TCM)  prescriptions or single compounds from both molecular and systemic perspectives.

It scientifically elucidates the pharmacological mechanisms of TCM. Built on the interaction network of “disease-gene-target-drug,” it emphasizes analyzing the molecular correlation patterns between drugs and their therapeutic targets from a systemic and holistic approach.

EB screening in the study identified 12 active ingredients and 161 gene targets for glaucoma treatment.

EB was found to have pharmacological effects such as vasodilation, improvement of microcirculation, and enhancement of blood supply to the heart and brain; regulation of blood lipids, reduction of blood viscosity, and improvement of blood rheology; inhibition of platelet and red blood cell aggregation, promotion of fibrinolytic activity; scavenging of oxygen free radicals, combating lipid peroxidation, and ischemia-reperfusion injury.

The main chemical components of EB have been gradually revealed and elucidated. 

This study identified 50 active components through Traditional Chinese Medicine Systems Pharmacology screening, including quinic acid, ethyl caffeate, and methyl caffeate, all of which are caffeoyl ester compounds. Among the 12 effective active components, most are flavonoids, such as luteolin, quercetin, kaempferol, naringenin, 6-hydroxykaempferol, and baicalein.

Based on network pharmacology, the researchers identified the action targets of 12 active components and the disease targets of glaucoma, and then found the intersection, resulting in a total of 161 targets for EB in the treatment of glaucoma. 

By constructing the drug-active ingredient-target-disease network diagram, it can be seen that EB exhibits a multi-component, multi-target action mode in the treatment of glaucoma.

EB may protect or restore optic nerve function in the treatment of glaucoma by promoting cell proliferation, inhibiting apoptosis.

Therefore, EB treatment of glaucoma is a complex process involving multiple components, multiple target actions, and multi-pathway coordination.

REFERENCE:

Yang E, Zhu Y, Chen X, Xie X, Ma Z. Exploring the potential mechanisms of Erigeron breviscapus in the treatment of glaucoma based on network pharmacology and molecular docking. Medicine (Baltimore). 2025 Aug 15;104(33):e43970. doi: 10.1097/MD.0000000000043970. PMID: 40826712; PMCID: PMC12366968.

BRINZOLAMIDE

 

Brinzolamide is a carbonic anhydrase inhibitor (CAI) used to lower intraocular pressure (IOP) in patients with open-angle glaucoma (POAG) or ocular hypertension (OH).

Brinzolamide is commonly available as a 1% suspension. It can be used in patients unresponsive to beta-blockers or in whom beta-blockers are contraindicated.

Pharmacodynamics:

Pharmacologically, brinzolamide is a highly specific, non-competitive, reversible, and effective inhibitor of carbonic anhydrase II (CA-II). It is able to suppress the formation of aqueous humor in the eye presumably by reducing the rate of formation of bicarbonate ions with subsequent reduction in sodium and fluid transport; and thus, decrease IOP.

Brinzolamide can be added to beta-blockers and prostaglandins. In the latter combination, prostaglandin derivatives improve the uveoscleral outflow but also increase the activity of CA in ciliary epithelium which may lead to a secondary increase in aqueous humor secretion. This may slightly reduce the efficacy of prostaglandin analogues. Topical CAIs inhibit CA-II, thus overcoming the increased ciliary body activity of prostaglandin analogues, and indirectly improving prostaglandin efficacy. 

Brinzolamide could have a secondary possible effect on ocular flow too. Some clinical studies have shown a mild improvement of ocular blood flow.

Pharmacokinetics:

The recommended frequency for topical application is two to three times per day. As monotherapy in patients with POAG or OH, brinzolamide 1% demonstrated IOP-lowering efficacy that was significantly greater than placebo, equivalent to three-times-daily dorzolamide 2% but significantly lower than twice-daily timolol 0.5%. 

Phase III trials have reported that brinzolamide 1% twice- and thrice-daily produced statistically significant IOP reductions from baseline, and that both treatments were clinically equivalent to one another.

Both regimens produce diurnal mean IOP reductions from baseline in the range of 13.2-21.8%.

Side effects:

In clinical trials, brinzolamide 1% was well tolerated causing only non-serious adverse effects that were generally local, transient and mild to moderate in severity. The incidence of the most common adverse events associated with the use of brinzolamide 1% was either similar to (blurred vision and abnormal taste) or significantly lower than (ocular discomfort) with dorzolamide 2%.

Common, but mild side effects: blurred vision; bitter, sour, or unusual taste; itching, pain, watering, or dryness of the eyes; feeling that something is in the eye; headache; runny nose

Rare, but serious: fast or irregular heartbeat; fainting; skin rash, hives, or itching; severe eye irritation, redness, or swelling; swelling in the face, lips, or throat; wheezing or trouble breathing

Precautions:

• Hypersensitivity to other sulfonamides
• Acute angle-closure glaucoma
• Concomitant administration of oral carbonic anhydrase inhibitors
• Moderate-to-severe chronic kidney disease or liver disease.

Corneal decompensation:

In the corneal endothelium, CA-II plays a role in the pumping mechanism, which helps to maintain the relatively dehydrated state of the corneal stroma. Inhibition of this mechanism can cause corneal decompensation and edema, which leads to impaired vision. 

In a randomized, double-blind clinical trial, 372 glaucomatous and OH patients received brinzolamide 1% or timolol 0.5%. After 18 months of treatment, no significant change was found in corneal thickness and corneal endothelium cell density. However, in this study only subjects with healthy corneas were included. Some concern remained in patients with compromised corneas, because in 2 published case reports corneal decompensation has been described in patients with keratopathy after treatment with dorzolamide. 

ALSO SEE= "FIXED DRUG COMBINATIONS": 

https://ourgsc.blogspot.com/2019/10/fixed-drug-combinations-in-glaucoma.html