ADVERSE EFFECTS OF ANTI GLAUCOMA MEDICATIONS

Adverse reactions to anti-glaucoma eyedrops can occur either due to the main active ingredient or from the additive agents, especially preservatives.

Preservatives extend the shelf-life of drugs and have sterilising or bacteriostatic properties.

Most preservatives also act as surfactants which destabilize bacterial cell membranes. This causes destruction of the cell membrane, inhibition of cell growth, and reduction of cell adhesiveness. However, preservatives also exert these effects on normal corneal and conjunctival cells, resulting in ocular surface disorders such as superficial punctate keratitis, corneal erosions, conjunctival allergy, conjunctival injection, and anterior chamber inflammation.

Adverse reactions to topical medications can be limited to the eye or occur systemically. The latter usually occur as the drug is absorbed through the nasal mucosa and enters the blood circulation. This is one reason why patients are advised to include the puncta when instilling the drops.

BETA BLOCKERS:

Ocular adverse reactions to β-blockers include conjunctival allergies, conjunctival injection, corneal epithelium disorders, blepharitis, and ocular pemphigoid. 

Betoxolol reduces corneal sensitivity due to a local anaesthetic effect (membrane-stabilizing effect). The subsequent reduction in reflex tearing may lead to corneal epithelial disorders.

Carteolol has intrinsic sympathomimetic activity so administration of this drug does not lead to a reduced corneal sensitivity. Therefore, carteolol administration is associated with fewer cases of corneal epithelium disorders compared to other beta blockers such as timolol.

Systemic adverse reactions of the circulatory system caused by β1-blockers includes bradycardia, hypotension, and an irregular pulse. Adverse effects of the respiratory system are caused by β2-blocker activity and include worsening of asthma attacks and chronic obstructive pulmonary disease. Patients may also experience symptoms of the central nervous system, including headaches, depression, anxiety, confusion, dysarthria, hallucinations, somnolence, and lethargy. 

Vasodilatation occurs with carteolol, which has intrinsic sympathomimetic activity, so adverse reactions mentioned above do not often appear after carteolol administration. 

Betaxolol is a selective β1-blocker with few adverse reactions because it is the β2-blockers that affect the respiratory system.

Nipradilol is a β-blocker and an α1-blocker, but has few systemic side effects because of the weaker β-blocker activity.

PROSTAGLANDIN ANALOGUES:

Ocular adverse reactions such as 

conjunctival allergy, conjunctival hyperemia, corneal epithelial disorders, and blepharitis are characteristic adverse reactions associated with prostaglandin analogs (PAs). Patients receiving these drugs might have eyelash bristling/lengthening, vellus hair, eyelid pigmentation, iris pigmentation, and deepening of the upper eyelid sulcus (DUES).

In the initial stages of treatment with PAs, patients often have intense conjunctival hyperemia, but this gradually decreases over time. A meta-analyses has shown that conjunctival hyperemia occurred significantly less often with latanoprost than with travoprost (odds ratio =0.512) or with bimatoprost (odds ratio =0.32). However, there are conflicting reports regarding which PA causes more hyperemia. 

Eyelash lengthening and eyelid pigmentation appear to be the same with all PAs. Iris pigmentation often occurs in Europeans and Americans, in whom iris pigments are green-brown, yellow-brown, blue-brown, and/or of mixed color.

DUES occurred in 60%, 50%, 24%, and 18% of patients using bimatoprost, travoprost, latanoprost, and tafluprost, respectively.

In anamnestic cases involving corneal epithelium herpes, recurrent herpes was reported to occur and progress with latanoprost administration. Therefore, caution should be used when prescribing prostaglandin analogs in these patients. Macular edema has also been reported after latanoprost administration following cataract surgery.

No systemic adverse reactions have been reported with prostaglandin analog use.

CARBONIC ANHYDRASE INHIBITORS:

Ocular adverse reactions associated with carbonic anhydrase inhibitors include conjunctival allergy, conjunctival hyperemia, corneal epithelial disorders, blepharitis, Stevens–Johnson syndrome, and toxic epidermal necrosis. Dorzolamide is viscous and has a fairly acidic pH (pH =5.5–5.9), which generally causes ocular irritation. Because intraocular transitivity is slightly poor, foreign body sensation and blurred vision often occur in patients receiving brinzolamide.39 More over, carbonic anhydrase naturally exists in the corneal endothelium, and caution is needed in patients with corneal endothelial disorders.

No systemic adverse reactions were associated with topical carbonic anhydrase inhibitor use.

Ocular adverse reactions associated with parasympathomimetic drugs (Pilocarpine) included miosis-caused aphose, visual field constriction, and night vision loss. Near sightedness could also occur because of stress on ciliary muscles and patients may be conscious of haze. Ocular pemphigoid, cataract, and retinal detachment may also occur.

Systemic adverse reactions

Increases in parasympathetic nervous system activity of the internal organs may result in higher secretory gland activity and cause stress on smooth muscles. As a result, drooling, sweating, diarrhea, nausea/vomiting, stomachache, asthma, bradycardia, hallucinations and depression may occur with parasympathomimetic medication use.

SYMPATHETIC ALPHA -1 ANTAGONISTS:

Ocular adverse reactions to sympathetic α1-receptor antagonists included conjunctival hyperemia, foreign body sensation, and blepharitis.

Systemic adverse reactions to sympathetic α1-receptor antagonists included headaches and a throbbing sensation, both of which were mild.

SYMPATHOMIMETICS:

Ocular adverse reactions to sympathomimetic drugs (Dipivefrin) included burning sensation, irritation, conjunctival injection and pupil dilation. Ocular pemphigoid had also been observed in some patients and epinephrine maculopathy could occur in aphakic patients.

Systemic effects affect the cardiac system and adverse reactions include increases in systemic blood pressure, tachycardia and irregular pulse. The respiratory effects include coughing, difficulty breathing and bronchitis. Adverse reactions related to the neuropsychiatric system include sleeplessness, depression, nervousness, and trembling. Finally, digestive system reactions include gastrointestinal disorders, taste disorders, and nausea.

SYMPATHETIC ALPHA-2 ANTAGONISTS:

Ocular adverse reactions associated with long-term sympathetic α2-receptor antagonist (brimonidine and apraclonidine) use include hyperemia conjunctivae, pale conjunctiva, pupil dilation, and allergic conjunctivitis.

Systemic adverse reactions associated with long-term sympathetic α2-receptor antagonist use includes decreases in blood pressure and pulse, drowsiness, dizziness, and dry mouth.

GLAUCOMA AS A CENTRAL NEURODEGENERATIVE DISEASE

  

The major length of the axon of the retinal ganglion cells (RGC) is extra-ocular, with pre-chiasmal, chiasmal and post-chiasmal components. Furthermore, 90% of RGCs project to the lateral geniculate nucleus (LGN), the first major vision center located deep within the brain. Therefore, glaucoma, in which RGC and axonal damage is prominent, has to be studied in terms of central connections and damages in those structures.

Recent advances in our understanding of the post-laminar changes in glaucoma vis-à-vis the mechanical theory of glaucoma have shed light on central changes occurring in this disease. [1]

Gupta and Yucel were among the first to suggest that elevated IOP and destruction of the RGCs could trigger transsynaptic degeneration in the lateral geniculate bodies (LGB) and visual cortex. This has led to the development of the central mechanism of glaucomatous neurodegeneration. [2]

A fundamental process shared by neurodegenerative diseases is the loss of specific neuron populations. Vision loss and dysfunction in glaucoma result from RGC death, atrophy, and axon degeneration extending to central visual targets in the brain. Changes similar to other neurodegenerative diseases such as Alzheimer’s and Parkinsons have been reported in glaucoma patients. Amyloid β protein deposits, synuclein, and pTau have been identified in the retina of glaucoma patients. [3]

Neurodegenerative diseases typically show a progressive decline in function related to the loss of relevant neuron systems, as seen in glaucomatous visual dysfunction in proportion to the RGC demise. The mode of disease spread in neurodegenerative disorders is called transsynaptic degeneration. Disease is transmitted from sick neurons to healthy neurons through synaptic connections along anatomic and functional neural pathways. This spread of disease between communicating neurons is a well-known feature of Alzheimer’s disease and Amyotrophic lateral sclerosis (ALS), and has more recently been described in experimental and human glaucoma. The extension of the neurodegenerative damage from the retina to the central visual pathways has the potential to disrupt the processing of visual information from the eye to the brain. [2]

Neuroinflammatory reactions, especially at the level of the glial and microglial cells have been reported in glaucoma patients; changes similar to those reported in neurodegenerative diseases. Various biochemical mechanisms have been proposed which cause damage to these neural structures. [4]

Shrinkage and loss of neurons, reduced metabolic activity, and dysfunction in the expression patterns of several markers of synaptic plasticity in the LGB and visual cortex appear in glaucoma disease and experimental primate models, after a period of increased IOP.

MRI imaging has shown degeneration of central visual pathways after damage to RGC axons. Degeneration of the lateral geniculate nucleus, genicular-cortical projections, and cortical areas themselves, have been explored in patients with glaucoma. 

MRI CHANGES IN GLAUCOMA:

https://ourgsc.blogspot.com/2025/12/mri-in-glaucoma-part-1.html

Researchers have reported a complex network of connectivity between different cortical areas, called the functional connectome. Profound functional reorganization of the entire brain in glaucoma patients has been found. [3]

Network disruption and the appearance-disappearance of specific hubs compared to healthy controls and a different spatial distribution in the density of functional connectivity on long or short-term in glaucoma. Two hub regions are absent in glaucoma patients: the gyrus right angular, situated in the anterolateral region of the parietal lobe, with the role in processing concepts rather than percepts in the perception-recognition-action interface and the left lobule VIIB of the cerebellar hemisphere (with a role in fine motor coordination, in the inhibition of involuntary movement by inhibitory neurotransmitters). In contrast, three hubs were present only in glaucoma patients: the right inferior occipital cortex - the region is located in the occipital lobe, which contains the primary visual pathway, the right inferior temporal gyrus, located in the temporal lobe, a key area involved in the simple processing of the visual field] and the left lobule IX of the cerebellar hemisphere, an area considered essential for the visual guidance of movement. [3]

Central visual pathway degeneration in glaucoma is a process that may begin early in the disease. For example, in primate glaucoma, elevated IOP may not show measurable optic nerve fiber loss but is found to induce shrinkage of target LGN neurons. Chronic ocular hypertension also induces significant dendrite pathology in the LGB. Transsynaptic injury to LGN neurons may thus be induced following RGC injury in the absence of detectable RGC death. [2]

In a case of human glaucoma, postmortem analysis of the visual system correlated optic nerve damage and visual field deficits, and revealed neuropathology in the intracranial optic nerve, LGN and visual cortex in a retinotopic fashion. [2]

Marked central visual system degeneration may be a factor in patients who show progressive glaucomatous damage despite well controlled IOP.

REFERENCES:

1. Ahmad SS. The mechanical theory of glaucoma in terms of prelaminar, laminar, and postlaminar factors. Taiwan J Ophthalmol. 2023 Dec 21;14(3):376-386. doi: 10.4103/tjo.TJO-D-23-00103. PMID: 39430347; PMCID: PMC11488796.
2. Gupta N, Yücel YH. Glaucoma as a neurodegenerative disease. Curr Opin Ophthalmol. 2007 Mar;18(2):110-4. doi: 10.1097/ICU.0b013e3280895aea. PMID: 17301611.
3. Neacșu AM, Ferechide D. Glaucoma - a neurodegenerative disease with cerebral neuroconnectivity elements. Rom J Ophthalmol. 2022 Jul-Sep;66(3):219-224. doi:
   10.22336/rjo.2022.43. PMID: 36349168; PMCID: PMC9585488.
4. Shoeb Ahmad S, Abdul Ghani S, Hemalata Rajagopal T. Current Concepts in the Biochemical Mechanisms of Glaucomatous Neurodegeneration. J Curr Glaucoma Pract. 2013 May-Aug;7(2):49-53. doi: 10.5005/jp-journals-10008-1137. Epub 2013 May 9. PMID: 26997782; PMCID: PMC4741173.

TANITO MICROHOOK TRABECULOTOMY

The Tanito microhook trabeculotomy (TMH), also called the Microhook ab interno trabeculotomy (µLOT), is a novel minimally invasive glaucoma surgery (MIGS).

The procedure incises trabecular meshwork using small hooks that are inserted through corneal side ports.

The Microhook can incise the inner wall of Schlemm’s canal without damaging its outer wall more efficiently than the regular straight knife that is used during goniotomy. 

The procedure involves standard sub-tenon anesthesia using 2% lidocaine or intracameral anesthesia using 1% lidocaine. Viscoelastic material is injected into the anterior chamber (AC) through the clear corneal ports created using a 20-gauge micro-vitreoretinal (MVR) knife at the 2–3 and 9–10 o’clock positions. Using a Swan-Jacob gonioprism lens to observe the angle opposite from the corneal port, a microhook is inserted into the AC through the corneal port. The tip of the microhook is then inserted into the Schlemm’s canal and moved circumferentially to incise the inner wall of the Schlemm’s canal and trabecular meshwork over 3 clock hours. Using the same procedure, trabeculotomy is performed in the opposite angle using a microhook that is inserted through another corneal port. After the viscoelastic material is aspirated, the corneal ports are closed by corneal stromal hydration.

During µLOT surgery, 3 types of microhooks, that is, straight, angled-right, and angled-left, are used. For operability, a straight hook is used to incise the nasal angle and the right-angled and left-angled hooks are used to incise the temporal angle.

Shoji Modification:

The original TMH has demonstrated consistent IOP-lowering effects and a favorable safety profile in multiple retrospective studies. However, it may be limited by suboptimal access to the temporal angle in eyes with narrow angles, deep anterior chambers, steep cornea, or deep-set orbits. The Shoji edition was developed to address these use-case constraints, featuring a longer shaft to improve reach, a slimmer posterior profile for smoother canal access, and a wider incision arc to achieve a broader trabecular incision. These design changes were intended to improve surgical control and reproducibility while maintaining reusability.

In a study comparing the original TMH procedure and the Shoji modification reported that at 12 months, surgical success was achieved in 46.4% of the original group and 50.1% of the Shoji group; at 24 months, the rates were 32.0% and 44.2%, respectively. Kaplan-Meier estimates showed no significant difference between groups (log-rank P = 1.000). Both groups achieved reductions from baseline in mean IOP and number of glaucoma medications at all time points. Postoperative complications were infrequent and comparable between groups.

Advantages:

Advantages of µLOT include: a wider extent of trabeculotomy (two-thirds of the circumference), a simpler surgical technique, being less invasive to the ocular surface, a shorter surgical time than traditional ab externo trabeculotomy, and no requirement for expensive devices.

Because there is no bleb involved in decreasing the IOP reduction, there is less likelihood of trabeculotomy causing vision-threatening complications, for example, flat AC, bleb leaks, hypotony maculopathy, choroidal detachment, and bleb infections that can occur after trabeculectomy performed with antifibrotic agents.

REFERENCES:

• Tanito, M. (2018). Microhook ab interno trabeculotomy, a novel minimally invasive glaucoma surgery. Clinical Ophthalmology, 12, 43–48. https://doi.org/10.2147/OPTH.S152406.
• Shoji T, Nishida T, Tanito M. Original vs Shoji Edition of Tanito Microhook Trabeculotomy Combined with Cataract Surgery: Comparative Clinical Outcomes. J Glaucoma. 2026 May 1;35(5):342-347. doi: 10.1097/IJG.0000000000002667. Epub 2026 Feb 9. PMID: 41662866; PMCID: PMC13105747.
• Sasidharan, Ajita; Shah, Paraali; Thulasidas, Mithun. Short-term outcomes of Tanito microhook ab interno trabeculotomy combined with phacoemulsification in primary open-angle glaucoma – A pilot study. Indian Journal of Ophthalmology 73(Suppl 2):p S250-S253, March 2025. | DOI: 10.4103/IJO.IJO_723_24 

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

PREVALENCE OF GLAUCOMA IN EUROPE AND PROJECTIONS TO 2050

 

Stuart et al have performed a “Two-stage, individual participant data meta-analysis” to provide updated glaucoma prevalence estimates and to quantify the current and future burden of disease in Europe.

The analysis is based on population-based European Eye Epidemiology Consortium studies with glaucoma prevalence data based on direct participant examination.

The analysis included 55415 adults ≥40 years of age (mean age, 65.6 years; 53.9% women) from 14 population-based studies (1991-2020).

The European Eye Epidemiology Consortium is a collaborative initiative of >50 European eye studies, including >180 000 participants, with the aim of promoting and facilitating epidemiologic research into common eye diseases.

The results of this analysis are as follows:

• Among the 55415 individuals included in the study, 2021 participants (3.65%) were found to have glaucoma with an age-standardized European prevalence of 2.99%.
• Older age and male sex were associated with higher prevalence.
• Despite regional and diagnostic differences in prevalence estimates, no temporal trend was identified. However, studies based on specialist opinion yielded the highest glaucoma prevalence estimate and those based on modified ISGEO criteria yielded the lowest.
• This is perhaps unsurprising given that ISGEO criteria rely on statistical cutoffs of vertical cup-to-disc ratio and cup-to-disc ratio asymmetry to define structural damage, potentially excluding cases of early disease or other characteristic features of glaucomatous optic neuropathy that may have been considered diagnostic in other studies.
• Primary open-angle glaucoma (POAG) accounted for 79.9% of all cases of glaucoma. Among other subtypes, primary angle-closure glaucoma (PACG) (9.1% of all cases) and secondary glaucoma (11.0% of all cases) were also found. 
• The prevalence for all types of glaucoma showed an increasing trend with age. However, a decline in PACG prevalence was observed after 80 years of age (PACG was most common between 60-74 years of age).
• More than half (56.4%) of cases were undiagnosed previously (new cases), with a higher proportion of undetected disease in younger participants, including >80% in those <55 years of age.
• Based on the analysis, in 2024 the burden of cases was estimated to be of 12.3 million individuals with glaucoma in Europe, including 6.9 million individuals with undiagnosed disease.
• Significant differences were found across geographic regions, with the lowest prevalence observed in Western Europe and the highest in Eastern Europe.
• Despite projections of an overall decline in total population (~11.8%) over the next 26 years, the number of glaucoma cases is projected to increase to 13.52 million (þ10.3%) by 2050. Thus, the burden of glaucoma patients is projected to grow by >1 million people by 2050 because of changing population age structure, with a preponderance of primary open-angle glaucoma.
• The annual rate of change is expected to slow, however, with a peak of 13.63 million cases reached by 2045, before a decline in total case numbers is seen.

The study concluded that:

The burden of glaucoma may be significantly underestimated if estimates are based solely on published summary statistics, rather than individual-level data, and this may have broader implications for other age-related conditions.

REFERENCE:

Stuart KV, de Vries VA, Schuster AK, Yu Y, van der Heide FCT, Delcourt C, Cougnard-Grégoire A, Schweitzer C, Brandl C, Zimmermann ME, Heid IM, Farinha C, Coimbra R, Luben RN, Hayat S, Khaw KT, Stingl JV, Pfeiffer N, Berendschot TTJM; Maastricht Study Consortium; Arnould L, Creuzot-Garcher C, Hogg R, Wright DM, Azuara-Blanco A, Vergroesen JE, Klaver CCW, Ramdas WD, Topouzis F, Giannoulis DA, Bikbov MM, Kazakbaeva GM, Jonas JB, Jansonius NM, Bourne RRA, Quigley HA, Foster PJ, Khawaja AP; European Eye Epidemiology Consortium. Prevalence of Glaucoma in Europe and Projections to 2050: Findings from the European Eye Epidemiology Consortium. Ophthalmology. 2025 Oct;132(10):1114-1124. doi: 10.1016/j.ophtha.2025.06.002. Epub 2025 Jun 9. PMID: 40499787.

MICRO INTERVENTIONAL DYNAMIC OUTFLOW CURVE (imDOC)

Micro-interventional dynamic outflow curve (miDOC) is a revolutionary technology developed by Professor Sean Ianchulev, from the New York Eye and Ear Infirmary (NYEE), USA.

While performing glaucoma procedures without miDOC, surgeons have no way of checking a patient’s exact ocular flow and pressure, a critical variable in the operating room. They can only check intraocular pressure before and after the procedure, which occasionally leaves unpredictable outcomes.

This has affected the precision of glaucoma surgery. Some surveys have reported more than 50 percent of the patients undergoing trabeculectomy and drainage device implants unable to achieve complete postoperative success and medication independence. In some cases, it is not until the follow-up appointment that ophthalmologists discover the procedure may not have worked and/or has possible complications.

miDOC allows eye surgeons to measure and respond to critical fluid dynamics inside the eye in real time – an advance that may significantly improve precision and outcomes in glaucoma and other ophthalmic procedures.

During surgery, miDOC enables continuous measurement of key parameters including:

1. Pressure
2. Flow
3. Outflow facility
4. Ocular rigidity/Compliance

These measurements provide new insight into how surgical interventions affect the eye in real time.

By providing real-time biometric feedback, miDOC has the potential to elevate glaucoma surgery to a new era of digital-guided precision.

NYEE is the only eye center in the US to use this technology and conduct the first-in-human clinical study. Surgeons started using it in patients in July 2025 and have completed the first 20 cases. According to investigators, all procedures were successfully completed with intra-operative biometric guidance.

Investigators at NYEE plan to further refine the technology and pursue regulatory pathways for broader clinical use. 

Slow-Coagulation Continuous-Wave Cyclophotocoagulation

 

Slow coagulation continuous wave trans-scleral cyclophotocoagulation (CW-TSCPC) is an emerging relatively noninvasive intervention that can be used in different patient populations. The procedure uses the traditional G-probe and continuous wave (CW) laser, with a modified balance of power and duration for enhanced safety compared to the conventional protocol.

Slow coagulation CW-TSCPC delivers photocoagulative laser energy to the ciliary body using a fixed lower power of energy over a longer duration, thereby theoretically decreasing the risk of collateral damage surrounding the ciliary body and severe inflammation from necrotic high energy disruption of the ciliary body.

The greater pressure-lowering effect observed with Slow coagulation CW-TSCPC may be attributed to more substantial structural changes in the ciliary body, whereas the micropulse (MP) technique does not appear to produce significant histologic changes.

The standardized technique involves the following parameters: 1250 mW, 4 s/spot, 20 spots, delivering a total energy of 100 J.

The recently described variation—the Double-Arc Slow-Coagulation protocol—employs a dual-row application strategy, divided in upper (ciliary body shadow) and lower (1.5 mm behind) arcs. Initial results with this technique have demonstrated favorable IOP control and a low rate of complications in the management of refractory glaucomas.

The most frequent complications reported in a study comparing Slow coagulation CW-TSCPC with MP-LT are clinically significant visual acuity loss (20.0% in the Slow coagulation CW-TSCPC group and 26.7% in the MP-LT group), transient anterior segment inflammation (30.0% vs. 23.3%), and transient corneal edema (13.3% vs. 20.0%). 

Pupillary abnormalities, cystoid macular edema, iris synechiae, and iris neovascularization occur with varying frequencies. Hypotony has been reported in 6% patients following Slow coagulation CW-TSCPC.

Pupillary abnormalities are often linked to a more anterior application of the laser, closer to the iris root.

A two-center, randomized, clinical trial in a population of patients with refractory glaucoma, Slow coagulation CW-TSCPC demonstrated superior IOP control, with fewer IOP-lowering medications and a lower rate of surgical failure compared to MP-LT over an 18-month follow-up. Fewer reapplications and additional surgeries were required in the Slow coagulation CW-TSCPC group.

Another study of pseudophakic glaucoma reported lowering of IOP from 27.5±9.8 mm Hg preoperatively to 16.1±6.3 mm Hg postoperatively with a mean percentage reduction of IOP of 42.1% and 75.7% of eyes having ≥20% decrease in their baseline IOP.

Another study in virgin eyes reported that 52.2% of the treated eyes had ≥20% reduction of IOP from baseline. Interestingly, the IOP reduction was noted to more in patients with higher baseline IOP (>21 mm Hg). Slow coagulation TSCPC treatment resulted in a significant decrease of glaucoma medications from 3.8±1.0 to 2.8±1.4 at baseline and last visit, respectively. 

These findings highlight Slow coagulation CW-TSCPC as a reliable technique for managing different types of patients with glaucoma.