WALKING 10,000 STEPS DAILY AND GLAUCOMA

 

In the 1960s, a Japanese company created a pedometer called ‘Manpo-kei,’ which translates to ‘10,000 steps meter.’ The number was chosen because it sounded catchy and promoted an active lifestyle. Therefore, the common 10,000 steps daily concept did not originate from any health organization guidelines. Instead, it was merely a trendy marketing idea. 

However, modern research has since validated the health benefits of walking more daily, even if 10,000 isn’t a strict requirement.

Walking 10,000 steps per day provides individuals with a specific goal. It helps people avoid a sedentary lifestyle, which is linked with health issues like heart disease, high blood pressure, high cholesterol, type 2 diabetes, certain cancers, osteoporosis, depression, and anxiety.

Studies show that increasing daily step count is associated with lower mortality risk, improved cardiovascular health, lower cardiovascular-associated mortality, a decreased cancer risk, and better metabolic function. 

Movement releases endorphins, helping to reduce stress and boost mood.

A study by Yuanbo et al, published in the recent edition of the Journal of Glaucoma, has shown that patients with primary open angle glaucoma (POAG) with average daily steps (ADS) of more than 10,000 exhibited higher papillary (optic disc) vessel density (VD) compared with those with ADS less than 10,000. This indicates that increasing daily steps, particularly exceeding 10,000 steps, may potentially enhance ocular blood flow. (1)

The study reported that papillary VD was significantly denser in the ADS >10,000 group (ADS:12782±2925) compared with that of the ADS ≤10,000 group (ADS:7418±1543).

Therefore, the 10,000 daily step routine can be a useful regimen for POAG patients to improve ocular blood flow. Vascular abnormalities have been associated with the development and progression of glaucoma. (2)

REFERENCE:

1. Liang, Yuanbo MD, PhD; Yu, Yun PhD; Wen, Xin MD; Wang, Mei MD, PhD; Lan, Yuqing MD, PhD; Pan, Xiafei MD,. Walking More Than 10,000 Steps Per Day May Be Associated With Increased Optic Disc Vessel Density in Patients With Primary Open Angle Glaucoma. Journal of Glaucoma 34(4):p 249-255, April 2025. | DOI: 10.1097/IJG.0000000000002548
2. Ahmad SS. Controversies in the vascular theory of glaucomatous optic nerve degeneration. Taiwan J Ophthalmol. 2016 Oct-Dec;6(4):182-186. doi: 10.1016/j.tjo.2016.05.009. Epub 2016 Aug 1. PMID: 29018738; PMCID: PMC5525630.

 

OPTIC NERVE STIMULATION (ONS) THERAPY

 

An innovative approach to glaucoma treatment is electrical stimulation of the retina and optic nerve.

In a study by Gall, transcutaneous electrical stimulation was applied through supra- and infra-orbital electrodes to the eyes of 82 patients diagnosed with optic neuropathies. The treated group had a significant improvement in visual field of 24% compared to baseline. This improvement persisted for at least 2 months. [1]

Another study by Ota involved five eyes of four patients suffering from POAG, who underwent transcorneal electrical stimulation. There was a significant linear relationship between changes in MD values and the number of electrical stimulation sessions, indicating partially restored visual fields (p < 0.01). [2]

However, a study by Rock in which transcorneal electrical stimulation was done the results were equivocal. Patients were randomized into three groups with no stimulation (sham), and electrical stimulation intensities below (subthreshold) or above (suprathreshold) individual phosphene thresholds. No statistically significant differences in visual fields between groups were reported. [3]

A study of optic nerve stimulation (ONS) by Erb et al involved 101 eyes in 70 patients (31 female, 39 male). The subjects included primary open-angle glaucoma (POAG, 65), normal tension glaucoma (NTG, 13), angle-closure glaucoma (ACG, 6), pseudoexfoliative glaucoma (PEX, 6), juvenile glaucoma (4), pigmentary glaucoma (4), glaucoma fere absolutum (2), and congenital glaucoma (1). [4]

The ONS treatment was conducted using the Eyetronic® device (Neuromodtronic GmbH, Potsdam, Germany) that applied electrical stimulation via goggles with embedded supraorbital and infraorbital electrodes and recorded EEG signals via an electrode cap.

The study revealed a significant change of MD by − 0.5 dB/year on average in visual field testing. MD significantly decreased from PRE 14.0 dB (median) to POST 13.4 dB (p < 0.01). 64 eyes in 49 patients showed constant or reduced MD as compared to baseline (PRE 13.4 dB vs. POST 11.2 dB). In 37 eyes of 30 patients, MD increased from PRE 14.9 dB to POST 15.6 dB.

Median MD at baseline before ONS treatment was 14 dB, more than 58% of eyes had an advanced vision loss with an MD > 12 dB, more than 80% of eyes were classified as moderate or advanced glaucoma, corresponding to an MD ≥ 6 dB.

The Eyetronic therapy involves the application of gentle electrical pulses, which stimulate the metabolism of neurons, restoring their function and stopping further cellular degeneration.

The therapy involves 10 sessions of 60 minutes each, applied over 10 consecutive days.

WEBSITE: https://eyetronic-therapie.de/en/

REFERENCES:

1. Gall C, Schmidt S, Schittkowski MP, Antal A, Ambrus GG, Paulus W, et al. Alternating current Stimulation for vision restoration after optic nerve damage: a randomized clinical trial. PLoS One. 2016;11(6):e0156134.
2. Ota Y, Ozeki N, Yuki K, Shiba D, Kimura I, Tsunoda K, et al. The efficacy of Transcorneal electrical Stimulation for the treatment of primary open angle Glaucoma: a pilot study. Keio J Med. 2018;67(3):45–53.
3. Rock T, Naycheva L, Willmann G, Wilhelm B, Peters T, Zrenner E, et al. Transcorneal electrical stimulation in primary open angle glaucoma. Ophthalmologe. 2017;114(10):922–9.
4. Erb C, Eckert S, Gindorf P, Köhler M, Köhler T, Neuhann L, Neuhann T, Salzmann N, Schmickler S, Ellrich J. Electrical neurostimulation in glaucoma with progressive vision loss. Bioelectron Med. 2022 Mar 31;8(1):6. doi: 10.1186/s42234-022-00089-9. PMID: 35361287; PMCID: PMC8969331

BREAST CANCER AND GLAUCOMA

 

PRE-PRINT:

Breast carcinoma is the most commonly occurring cancer among females. An estimated 2.3 million new cases of breast carcinoma are diagnosed annually worldwide. These patients have a potential risk of ocular complications, not only from the disease itself, but also due to side effects of medications such as corticosteroids and cytotoxic drugs used to treat breast cancers. [1] Metastases to the eye can affect almost every structure of the eye and adnexa, affecting vision and ocular motility from involvement of the extra-ocular muscles. Often, the ocular findings are the first indication of the disease involving the breast. [2]

Glaucoma can occur through diverse mechanisms in such patients. However, there are only a few case reports and studies available to understand the association between the two conditions. Glaucoma and breast carcinoma are two serious conditions affecting the morbidity and mortality of the affected patient. It would be an important exercise to assess the extent of association between these two conditions.

REFERENCES:

Łukasiewicz S, Czeczelewski M, Forma A, Baj J, Sitarz R, Stanisławek A. Breast Cancer-Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies-An Updated Review. Cancers (Basel). 2021 Aug 25;13(17):4287.

Swampillai AJ, Booth AP, Cohen VML. Ciliary body and iris metastases with anterior chamber angle infiltration: a rare complication from invasive ductal breast cancer. J Glaucoma. 2020;29:e12-e15.

CATCH OUR ARTICLE COMING SOON ON: TOUCHReviews in Ophthalmology

 

THABIT IBN QURRA

 

Thābit ibn Qurra (full name: Abū al-Ḥasan Ṯhābit ibn Qurra ibn Zahrūn al-Ḥarrānī al-Ṣābiʾ) was a scholar known for his work in mathematics, medicine, astronomy, and translation. He was born in 826 or 836 and died on February 19, 901.

Thābit was born in Harran in Upper Mesopotamia, which at the time was part of the Diyar Mudar subdivision of the al-Jazira region of the Abbasid Caliphate. He spent most of his life in Baghdad.

Thābit was a well-known physician of his time and produced several medical treatises and commentaries. His works included general reference books such as al-Dhakhira fī ilm al-tibb ("A Treasury of Medicine"), Kitāb al-Rawda fi l–tibb ("Book of the Garden of Medicine"), and al-Kunnash ("Collection").

Thabit was the first to describe occlusion therapy for treating lazy eye or amblyopia. He suggested the closure of the normal eye with a patch to strengthen the lazy eye by forcing the “visual spirit” to transfer into the lazy eye: This was a leading breakthrough in ophthalmology.

REFERENCES:

• Abudawood GA, Alshareef R, Alghamdi S. Arab and Muslim scientists and their contributions to the history of ophthalmology. Saudi J Ophthalmol 2020;34:198-201.
• https://en.wikipedia.org/wiki/Th%C4%81bit_ibn_Qurra

FIBRONECTIN for NERVE REGENERATION

 

The central nervous system (CNS) projection neurons do not regenerate after axonal injury or degeneration. 

Several intra- and extra-cellular factors have been discovered that regulate axon regeneration. However, it is still difficult to find mechanisms to bypass extracellular inhibitors associated with glial scar and myelin formation (e.g., Cspg, Mag, NogoA, OMgp, Semaphorins) and help regenerate a complete axon.

As the CNS matures, the retinal ganglion cells (RGCs) lose their ability for intrinsic axon growth. This happens with a change in the initial axonal preference for an extracellular matrix (ECM) substrate to grow, conferred by integrin α and β heterodimers. Changes in the extracellular environment compromise the function of neuronal integrin subunit expression and axonal growth following injury or other deleterious events.

Lukomska and colleagues found that an ECM substrate fibronectin (Fn) which interacts with integrins was excessively present in some RGCs that survived optic nerve crush injury. It was found that Fn promotes survival and axon regeneration of axotomized adult RGCs in culture without glial scar inhibitors.

Injury-activated macrophages/microglia upregulate Fn. These cells are recruited by axon regeneration-promoting zymosan. This increases the Fn levels in the injured area.

The researchers found that Fn’s RGD motif, which interacts with Itga5 and ItgaV promotes long-term survival and long-distance axonal regeneration of adult RGCs. Some of the axons were found to reach the optic chiasm when co-treated with rpl7a gene therapy.

In conclusion, augmenting Fn levels in the damaged CNS is a promising therapeutic neuroprotective and neuroregenerative approach.

REFERENCE:

Lukomska A, Rheaume BA, Frost MP, Theune WC, Xing J, Damania A, Trakhtenberg EF. Augmenting fibronectin levels in injured adult CNS promotes axon regeneration in vivo. Exp Neurol. 2024 Sep;379:114877. doi: 10.1016/j.expneurol.2024.114877. Epub 2024 Jun 27. PMID: 38944331; PMCID: PMC11283980.

 

KAHOOK DUAL BLADE vs iSTENT: A META-ANALYSIS

 

The Kahook Dual Blade (KDB) is a modern goniotomy device. The goal for inventing the KDB device was to find a better and more efficient method for removing a complete strip of trabecular meshwork (TM) using an ab interno approach while minimizing damage to surrounding tissues.

CHECK LINK: https://ourgsc.blogspot.com/search?q=kahook

The iStent is a minimally invasive glaucoma surgery (MIGS) device devised to bypass the obstructed TM and allow the flow of aqueous from the anterior chamber into the Schlemm’s canal.

CHECK LINK: https://ourgsc.blogspot.com/search?q=iStent

A systematic review and meta-analysis comparing the KDB with iStent implantation with phacoemulsification was done by Guedes et al.

Fourteen studies were included with a total of 1959 eyes (958 phaco-KDB, and 1000 phaco-Stent including 753 phaco-iStent and 207 phaco-iStent inject).

The combined findings showed significantly higher rates of surgical success in the phaco-KDB group versus the phaco-Stent group (odds ratio: 0.68; 95% CI: 0.50 to 0.92; P = 0.01; I2 = 40%), and greater IOP reduction in the phaco-KDB group versus the phaco-Stent group at month 6 (MD: 1.13 mm Hg; 95% CI: 0.43 to 1.83; P = 0.002; I2 = 51%).

By month 12, both groups demonstrated similar IOP reduction. Subgroup analysis at month 12 showed greater IOP reduction in the phaco-KDB group versus the phaco-iStent group (MD: 1.69 mm Hg; 95% CI: 0.44 to 2.95; P = 0.008; I2 = 74%). However, compared with the phaco iStent inject group, there was no significant difference in IOP reduction (MD: −0.72 mm Hg; 95% CI: −3.69 to 2.24; P = 0.63; I2 = 64%). Medication reduction and the incidence of adverse events were comparable between groups.

RESULT:

The study concluded that KDB goniotomy may offer better surgical success compared with Stent implantation when used in combination with phacoemulsification. KDB goniotomy demonstrated better IOP reduction at month 12 compared with iStent. However, iStent inject showed a similar IOP reduction to KDB.

REFERENCE:

Guedes J, Amaral DC, de Oliveira Caneca K, Cassins Aguiar EH, de Oliveira LN, Mora-Paez DJ, Cyrino LG, Louzada RN, Moster MR, Myers JS, Schuman JS, Shukla AG, Shalaby WS. Kahook Dual Blade Goniotomy Versus iStent Implantation Combined With Phacoemulsification: A Systematic Review and Meta-Analysis. J Glaucoma. 2025 Mar 1;34(3):232-247. doi: 10.1097/IJG.0000000000002522. Epub 2024 Dec 9. PMID: 39641580.

VisiPlate Glaucoma Shunt

 

The VisiPlate is an ultrathin, multichannel, nonfibrotic aqueous shunt, which can have significant advantages in glaucoma surgery.

It shunts aqueous humor from the anterior chamber through a network of open microchannels to the subconjunctival space.

VisiPlate’s metamaterial features a highly biocompatible alumina plate coated with Parylene C.  The device has a 400-nm aluminum oxide plate coated with a 2-µm-thick layer of Parylene C.

It is corrugated into a pattern of networked microchannels, forming a hexagonal honeycomb.

The network of highly tunable rectangular microchannels rather than a large single-lumen tube provides better stability to aqueous outflow. The VisiPlate design represents a unique approach to lowering IOP; the numerous microchannels in the device enable slow and controlled outflow and provide a multitude of pathways for redundancy.

Slow outflow can create a diffuse, low-lying bleb that avoids tension and results in greater patient comfort than an elevated bleb.

Additionally, a controlled reduction of IOP minimizes the risk of early suprachoroidal hemorrhage.

VisiPlate’s thin profile is designed to limit peri-device flow and provide greater comfort and better aesthetics for the patient, with less risk of microtraumas from eyelid movement. Additionally, the nonfibrotic nature of the device minimizes foreign body response and has the potential to be effective without antifibrotic agents.

The composite structure of the VisiPlate is flexible and allows the device to conform to the curvature of the globe.

A version of VisiPlate being evaluated in early feasibility trials is approximately 5 mm wide and 8 mm long.

The implantation of the device is simple, without the need for patch grafts and gonioscopes. A scleral tunnel is created after a peritomy and the end of the device is inserted into the anterior chamber. The device is secured to the sclera. Antifibrotic agents can be used, according to the surgeon’s preference.

In a rabbit study by Kao et al, the VisiPlate demonstrated statistically significant (p<0.05) intraocular pressure (IOP) lowering of 20-40% compared to baseline at each timepoint over three months in nine implanted eyes.

A recent human VisiPlate study, known as the VITA trial, initially enrolled 15 patients and currently has 9-month data on 6 of those patients. On average, those with VisiPlate experienced a 46% drop in IOP (from 24 mmHg at baseline to 12.3 mmHg), and a reduction in average medication use from 2.1 medications at baseline to 0.7 medications.

The multichannel design provides several potential advantages over a tubular design by minimizing the risk of postoperative hypotony, avoiding peri-device flow, and diffusing aqueous in all directions in the subconjunctival space to form and sustain a low-lying bleb.

HORSE HAIR AS GLAUCOMA IMPLANT

 

Glaucoma drainage devices (GDDs) are rapidly evolving.

There are many types of implants being used or in the pipeline for the management of intraocular pressure (IOP).

However, a look into the history of GDDs shows how the process was started by using horse hair for drainage of hypopyon (pus) initially, and later for aqueous drainage in cases of absolute glaucoma.

REFERENCES:

1. Rollett M, Moreau M. Traitement de hypopyon par le drainage capillary de la chambre anterieure. Rev Gen Ophtalmol 906;25:48–9.

2. Rollett M, Moreau M. Le drainage au crin de la chambre anterieure contre l’hypertonie et la douleur. Rev Gen Ophtalmol 907;26:289–92.

PA5108 and PA5346 IMPLANTS

 

PolyActiva, an Australian biopharma company, has developed a biodegradable latanoprost implant. The PA5108 Ocular Implant employs the proprietary Prezia™ Sustained Drug Delivery Technology to release a constant daily dose of latanoprost.

The rod-shaped implant is injected in the anterior chamber, where it sinks into the lower part of the angle, being heavier than aqueous.

The implant is made of biodegradable polymer and is mildly adhesive to the iris.

The implant leaches latanoprost with zero-order kinetics and degrades completely leaving no residue post-dissolution and minimizing adverse effects.

Phase II trial has shown:

• Statistically significant intraocular pressure (IOP) changes from baseline were observed for each mean diurnal measurement at Weeks 12, 21, 33, and 42 (p<0.0001).
• Clinically meaningful IOP reductions at 8 am over 48 weeks were observed, with mean IOP reductions between 26 and 35%.
• 94% of participants did not require additional drop therapy over the 48-week treatment period.
• Full implant biodegradation by week 40.

PolyActiva’s Phase 2 clinical trial involved 15 participants. There was more than 20% reduction in the IOP.

Studies have found the implant safe for the cornea, iris, and other intra-ocular structures. There was no inflammatory reaction to the implant.

The company also claims that latanoprost does not seep into the orbit, unlike topical drops which can cause prostaglandin analogue-induced orbitopathy. There is no ocular surface disease, dry eyes, or irritation with the implant, some common side-effects seen with drops.

The PA5346 Latanoprost FA SR Ocular Implant is a second-generation single-dose (100 ng/day) device that could function for 12 months.

3D-PRINTED BILAYER GDD

 

The proper production and drainage of aqueous humor from the eye maintains an intraocular pressure (IOP) in a normal range of 10 to 21 mmHg. Glaucoma management involves either decreasing the aqueous humor production or promoting its drainage out of the eye to achieve the required target IOP.

Glaucoma Drainage Devices (GDDs) reduce IOP by bypassing the normal aqueous humor outflow pathway and allowing the aqueous humor to drain freely through the device's drainage channels. However, some GDDs have a problem with increased flow in the early postoperative phase, causing hypotony.

In a study by Kim et al., 3D printing technology was used to improve conventional aqueous drainage devices. They fabricated a double-layered aqueous drainage tube using polycaprolactone (PCL) with different molecular weights. The high-molecular-weight PCL (for the outer layer) and low-molecular-weight PCL (for the inner layer) were used to fabricate an aqueous drainage tube with an inner diameter that could be expanded via biodegradation.

The bi-layered fabricated structure was composed of two completely distinct layers of PCL with an average outer diameter of 947.91 ± 73.31 µm and an average inner diameter of 661.15 ± 55.56 µm.

After 2 days of exposure to sodium hydroxide, the inner layer degraded with a decrease in the cross-sectional area and a corresponding increase in the average diameter.

The inner diameter expansion is possible by using low-molecular-weight PCL inside the tube. Therefore, it can drain less aqueous humor when the IOP is low during the early postoperative period, and the drainage is increased when the IOP is high during the late postoperative period.

This approach can avoid some of the complications seen with commonly used GDDs.

REFERENCE:

Kim, J.-S.; Jeong, H.-J.; Park, J.-W.; Gwak, S.-J.; Han, J.-S.; Jung, K.I.; Lee, S.-J. A 3D-Printed Aqueous Drainage Tube with an Expandable Inner Diameter to Accommodate the Intraocular Pressure (IOP) Fluctuations After Glaucoma Surgery. Polymers 2025, 17, 118. https:// doi.org/10.3390/polym17010118.

OBITUARY TO MY FATHER

The Glog has been dormant for the last week, as my father passed away on 8th of February after a brief illness. Although suffering from Alzheimer's disease for the last two years he was mobile and eating well. Suddenly, his health deteriorated and he passed away in his sleep.

He was a major influence in my life both personally and professionally. He had taught Botany at a college for almost half a decade. He was extremely conscientious, and performed his duties without any fear or favor. He was honest to the core and refused to do anything which would affect his conscience. Once I asked him to bring 2 pieces of chalk from his college. However, he refused, saying his conscience doesn't allow even that.

He was always well-dressed. His shoes shone bright, which he himself polished daily. 

When I wrote any article it was my father who acted as my editor. He would correct any grammatical mistakes and also would ask me about the research I was doing.

My family has lost a loving and caring father and grandfather.

The Glog shall always remember and pray for him.

DRUG-INDUCED GLAUCOMA

 

Almost 50 topically and systemically administered drugs have been found to cause temporary or chronic intraocular pressure (IOP) elevation, sometimes causing glaucomatous changes.

The mechanisms of IOP elevation occur through both closed-angle and open-angle patho-physiologies.

Ultrasound biomicroscopy (UBM) is occasionally required to confirm the cause and rule out conditions such as accommodative spasm and primary angle closure.

OPEN-ANGLE GLAUCOMA

Corticosteroids:

Details about steroid-induced glaucoma are presented here: 

https://ourgsc.blogspot.com/search?q=steroid

Patients have been categorized by Armaly and Becker into three categories depending on their response to topical steroids. Five percent of the population are high responders, developing an IOP increase >15 mm Hg and IOP >31 mm Hg after daily corticosteroid use for 4 to 6 weeks. Moderate responders, approximately one-third of the population, exhibit increased IOP of 6 to 15 mm Hg and have IOP between 20-31 mm Hg. Approximately two-thirds of the population are non-responders, with pressure increases of <6 mm Hg and IOP of <20 mm Hg.

Most studies have reported an increase in IOP between 3-6 weeks after topical steroid use.

Risk factors for high responders are patients with primary open-angle glaucoma and their first-degree relatives; elderly or young (<6 years) patients; and patients with type 1 diabetes or connective tissue disease (especially rheumatoid arthritis), high myopia, and angle recession glaucoma are at greater risk of steroid-induced glaucoma.

The likelihood of IOP elevation with systemic steroids seems to be less than with the topical route.

Tripathi et al found a significant relationship between IOP and the dose of corticosteroid administered (1.4 mm Hg increase in mean IOP for each 10 mg increase in the average daily prednisolone dose).

Fluorometholone, medrysone, rimexolone, and loteprednol are less potent topical corticosteroids with a lower risk of a rise in IOP.

Steroids increase the resistance to aqueous outflow through the trabecular meshwork.

The exact mechanisms are unknown but probably involve changes in the microstructure of the trabecular meshwork (cross-linked actin network formation) and cell activities causing decreased proliferation, migration, and phagocytosis of trabecular meshwork cells. These all cause progressive accumulation of extracellular debris and increased aqueous outflow resistance.

There is also increased production and deposition of glycosaminoglycan, elastin, fibronectin, laminin, and collagen type IV, coupled with decreased destruction from steroid-induced inhibition of matrix metalloproteinase inhibitors leading to increased outflow resistance.

In short, it includes discontinuation of the steroid or replacement with a non-steroidal anti-inflammatory agent and medical or occasionally surgical control of IOP.

Anecortave acetate is an angiostatic steroid synthesized from cortisol acetate. In a case series, a total of 8 eyes with medically uncontrolled intraocular pressure after steroid therapy, a periocular depot injection of anecortave acetate reduced the mean baseline intraocular pressure by 34.5% at one month. The mechanism underlying the effect seen with this agent is unclear.

Antineoplastic Agents:

Docetaxel, paclitaxel, as well as Imatinib mesylate, have been reported to increase IOP in one patient each.

Spasmolytics:

Propantheline bromide and dicyclomine have been documented to elevate the IOP in patients with open-angle glaucoma.

 CLOSED-ANGLE GLAUCOMA

Drug-induced acute angle-closure glaucoma (AACG) is seen in individuals at risk for occludable angles.  The risk factors for AACG include race (Asians, Inuit Eskimos, and Hispanics), older age, female gender, hyperopia (farsightedness, wearing plus glasses that magnify objects), narrow-angle, family history positive for angle closure, and previous angle closure in the fellow eye.

A database analysis of the FDA Adverse Event Reporting System (FAERS) by Aftab et al found the 50 most common drugs associated with angle-closure glaucoma. [SEE FIGURE] The most frequently reported drugs included topiramate (520 reports), citalopram (69 reports), levothyroxine (68 reports), escitalopram (58 reports), duloxetine (45 reports), and salbutamol (44 reports). The most frequently reported drug category was sulfonamides (642 reports), specifically topiramate. Serotonergic agents were the second-most commonly reported class of drugs at 318 reports.

Tropicamide and acetazolamide were other drugs associated with angle-closure glaucoma.

Sulfa Agents:

Sulfa drugs like topiramate, a sulfamate-substituted monosaccharide antiepileptic agent, precipitate AACG by inducing ciliary body edema, idiosyncratic lens swelling, shallowing of the anterior chamber, choroidal effusion, and retinal edema. Typically, this AACG is a bilateral non-pupillary block angle-closure glaucoma that occurs within the first several doses of the medication.

Drug-induced changes in membrane potential have been hypothesized to cause ciliary body edema, leading to relaxation of zonules and resultant lens thickening. Anterolateral rotation of the ciliary body about its attachment to the scleral spur leads to anterior displacement of the lens and iris and concomitant shallowing of anterior chamber. Associated choroidal detachment and supraciliary effusion are known to occur.

The fact that effusion occurs only in a few patients taking topiramate and, more importantly, it typically occurs on doses well within the normal therapeutic range and in patients with normal anterior chamber depth suggests an idiosyncratic etiology.

No known risk factors exist for this syndrome.

Other sulfa-based drugs known to be associated with AACG include acetazolamide, hydrochlorothiazide, cotrimoxazole, quinine and tetracycline.

Patients usually develop blurred vision from the induced myopia from the anterior lens movement. Glaucoma is reported between days 1 and 49 (average 7) after drug initiation. In 85%, the glaucoma developed within the first 2 weeks of initiation of the drug.

The condition usually resolves after discontinuation of the agent. However, one case of permanent IOP elevation after withdrawal has been reported.

Antidepressants:

Tricyclic agents, amitriptyline, and imipramine, and the non-tricyclic drugs mianserin hydrochloride, paroxetine, fluoxetine, fluvoxamine, citalopram, and escitalopram have been associated with AACG. The glaucoma arises as the result of the anticholinergic action of these medications, which produces mydriasis and blockage of the angle. Supraciliary effusion seen on UBM has also been identified as a pathogenetic mechanism.

Monoamine Oxidase Inhibitors:

These antidepressant agents have weak anti-cholinergic effects. When these agents are prescribed along with other drugs having anti-cholinergic properties, the possibility of angle-closure glaucoma increases.

Phenelzine sulfate and tranyl-cypromine sulfate have been reported to induce AACG.

Antipsychotics:

Antipsychotics have a relatively weaker anticholinergic action on the ocular smooth muscles compared with tricyclic antidepressants, and the risk of these causing glaucoma is lower.

Perphenazine, trifluoperazine, and fluphenazine have been reported to induce glaucoma.

Antihistamines:

The H1 and H2 receptor blockers also have anticholinergic activity that may induce glaucoma through pupillary mydriasis.

Promethazine has been shown to produce an idiopathic swelling of the lens that could increase the risk of pupillary block AACG. Cimetidine and ranitidine have been reported to increase IOP in a patient being treated for duodenal ulcer.

Anti-Parkinson's:

Trihexyphenidyl has been shown to precipitate AACG in susceptible individuals. The drug can also have prolonged cumulative effects causing creeping angle-closure glaucoma.

Orphenadrine also has been documented to precipitate AACG.

Sympathomimetics:

Alpha-adrenergic agents, especially those with alpha-1 agonistic activity, cause mydriasis that can precipitate AACG.

Phenylphrine eye drops for pupillary dilation and systemically for flu, anesthesia or locally for epistaxis can precipitate AACG.

Apraclonidine, an alpha-2 agonist eyedrop and dipivefrin, an antiglaucoma eyedrop, can cause acute angle-closure.

Parasympatholytics:

Nebulized ipratropium bromide and tiotropium bromide for obstructive pulmonary disease can cause acute angle-closure attack. The drug can leak through face masks and get absorbed through cornea and conjunctiva.

Scopolamine, an anti-emetic, can cause AACG in susceptible individuals.

Parasympathomimetic Agents:

Pilocarpine is an antiglaucoma medication, while acetylcholine and carbachol are used to constrict the pupil during intraocular surgery. These agents can rarely induce AACG because of anterior movement of the iris-lens diaphragm especially in eyes with zonular weakness and exfoliation syndrome.

Botulinum Toxin:

Used for blepharospasm, it can cause pupillary dilation when injected peri-ocularly. The postulated mechanism is diffusion of the drug towards the ciliary ganglion and impedance of cholinergic innervation of the pupil.

Cardiac Agents:

Disopyramide phosphate seems to have anticholinergic activity and may induce AACG.

There are mixed reports about the effect of calcium channel blockers on IOP.

Anticoagulant Therapy:

Anticoagulant therapy, in the form of heparin as well as low molecular weight heparin (enoxaparin, warfarin), can cause AACG by inducing massive vitreous, choroidal or subretinal hemorrhage.

Risk factors for the same include anticoagulants, exudative age-related macular degeneration and nanophthalmos.

Anesthetic Agents:

Succinylcholine and ketamine can elevate IOP. Usually, the IOP elevation is temporary.

Anticholinergic (atropine, scopolamine, and muscle relaxants) or adrenergic (ephedrine, epinephrine) anesthetic agents can also cause AACG.

TAKE HOME MESSAGE:

• It is important for the physician to be aware of risk factors that can precipitate AACG. A patient wearing thick glasses that magnifies objects suggests a hypermetropic error and crowding of the anterior segment.
• A quick torchlight examination by throwing light in the anterior chamber from the sides can show shallowness in predisposed eyes.
• Ophthalmological consultation is warranted in a predisposed patient before starting treatment with drugs capable of potentiating AACG.
• Any patient who has a red eye and subjective vision loss postoperatively (after anesthesia) should be examined urgently. Sometimes, the patient may not be able to convey his symptoms, such as blurred vision and pain, occurring from the elevated IOP, due to the anesthetic effect. A high index of suspicion should be kept for such cases.

REFERENCES:

1. Razeghinejad MR, Myers JS, Katz LJ. Iatrogenic glaucoma secondary to medications. Am J Med. 2011 Jan;124(1):20-5. doi: 10.1016/j.amjmed.2010.08.011. Epub 2010 Nov 17. PMID: 21092926.
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