TADALAFIL (CIALIS) & RISK OF GLAUCOMA

This post is based on a multinational cohort study, to assess the risk of glaucoma among patients using tadalafil (Cialis) for lower urinary tract symptoms.

Introduction:

Tadalafil (commonly known by the brand name Cialis) is a prescription medicine used to treat erectile dysfunction (ED), benign prostatic hyperplasia (BPH) or enlarged prostate, and pulmonary arterial hypertension. 

A multinational, retrospective cohort study was conducted using the TriNetX database by Hsia et al, and recently the results were reported in the British Journal of Ophthalmology.

The aim of the study was conducted to evaluate the association between tadalafil use for lower urinary tract symptoms (LUTS) and the risk of developing glaucoma.

Men aged ≥40 years with a history of LUTS were enrolled between 2012 and 2022. Individuals with a history of glaucoma prior to cohort entry were excluded. Participants were categorised into the tadalafil group and the non-phosphodiesterase type 5 inhibitor (non-PDE5i) group. Propensity score matching (1:1) was conducted to balance age, race, comorbidities, renal function and concomitant medications. Hazard ratios (HRs) were estimated for incident glaucoma of different subtypes and initiation of glaucoma treatment.

Results:

The cohort included 36927 tadalafil users and 36927 matched non-PDE5i users. 

Up to 5 years, tadalafil use was associated with an increased risk of glaucoma compared with non-PDE5i use (HR 1.22; 95% CI 1.12 to 1.33). Elevated risks were observed for ocular hypertension (HR 1.32; 95% CI 1.06 to 1.65), primary open-angle glaucoma (HR 1.33; 95% CI 1.05 to 1.67) and initiation of glaucoma treatment (HR 1.33; 95% CI 1.20 to 1.47). No significant associations were found for low-tension or primary angle-closure glaucoma. Tadalafil users had a higher 5-year cumulative incidence than non-users (3.93% vs 3.16%; p<0.001), with consistent risk in men >50 years, white population and across comorbidities, remaining robust to 1-, 3- and 6-month lag times.

Conclusions:

Tadalafil was associated with increased risk of glaucoma compared with non-PDE5i users in males with LUTS. Ophthalmic evaluation and follow-up may be considered, particularly in patients with risk factors for glaucoma.

REFERENCE:

Hsia Y, Tsai CY, Hung SC, Chen JP, Pan SY, Lin HJ, Wang IJ, Weng CH, Nam MH, Chou CC. Risk of glaucoma among patients using tadalafil for lower urinary tract symptoms: a multinational cohort study. Br J Ophthalmol. 2026 Aug 4:bjo-2026-329957. doi: 10.1136/bjo-2026-329957. Epub ahead of print. PMID: 42552102.

BIMATOPROST GRENOD NCX 470

INTRODUCTION:

A unique glaucoma medication, containing a proprietary nitric oxide (NO) donating platform and Bimatoprost is under FDA review. This dual action investigational drug is called NCX 470, also known as bimatoprost grenod.

The U.S. regulatory review process was started in July 2026 after Kowa (Japan) submitted a New Drug Application (NDA) for NCX 470 to the U.S. FDA.

MECHANISM OF ACTION:

The agent is unique in that it combines two pharmacological approaches in a single molecule:

• Bimatoprost — a prostaglandin-analogue that promotes uveoscleral outflow.
• Nitric oxide (NO) — a signaling molecule that enhances aqueous humor outflow through the conventional trabecular pathway.

The novel drug lowers IOP by acting on both major aqueous outflow pathways. By targeting these pathways simultaneously, researchers hope to achieve substantial IOP reduction.

TRIALS:

NCX 470 has been studied in a Phase 2 trial, Dolomites and in a Phase 3b trial, Whistler, and a separate Phase 3 program is ongoing in Japan. Exploratory nonclinical studies in a well-defined model with optic nerve head and retina damage (ET-1-induced ischemia/reperfusion) investigated the NCX 470 effects beyond its IOP lowering properties. The results suggest that NCX 470 improves ocular perfusion and restores retinal function in damaged eyes compared to vehicle and to Bimatoprost and may therefore have protective properties for the retina. Beneficial effects of NCX 470 have additionally been demonstrated in an in vivo model of retinal cell damage.

NCX 470 has completed two major Phase 3 studies:MONT BLANC and DENALI.

In the MONT BLANC study, 661 participants were analyzed. NCX 470 0.1% produced IOP reductions of approximately 8.0–9.7 mmHg across the evaluated time points and showed greater mean IOP reductions than latanoprost at all six measured time points, reaching statistical significance at four of them. 

The DENALI Phase 3 program also met its primary non-inferiority objective compared with latanoprost, supporting the subsequent U.S. NDA submission. 

SIDE-EFFECTS:

Clinical trials have reported a few ocular adverse events, with conjunctival/ocular hyperemia among the most common in the MONT BLANC study. 

REFERENCES:

1. Impagnatiello F, Toris CB, Batugo M, Prasanna G, Borghi V, Bastia E, Ongini E, Krauss AH. Intraocular Pressure-Lowering Activity of NCX 470, a Novel Nitric Oxide-Donating Bimatoprost in Preclinical Models. Invest Ophthalmol Vis Sci. 2015 Oct;56(11):6558-64. doi: 10.1167/iovs.15-17190. PMID: 26457541.
2. Fechtner R, Mansberger S, Branch J, Mulaney J, Ziebell S, Lopez K, Hubatsch D. A Randomized, Controlled Comparison of NCX 470, a Nitric Oxide-Donating Bimatoprost, and Latanoprost in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The MONT BLANC Study. Am J Ophthalmol. 2024 Aug;264:66-74. doi: 10.1016/j.ajo.2024.03.002. Epub 2024 Mar 16. PMID: 38499140.
3. Elena Bastia, Nicoletta Almirante, Michael V W Bergamini, Tomas Navratil, Marlene Woodruff Modi, Francesco Impagnatiello; Nonclinical development of NCX 470, a novel nitric oxide (NO)-donating,IOP lowering prostaglandin analog for glaucoma and ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3806.
4. https://www.medchemexpress.com/bimatoprost-grenod.html?srsltid=AfmBOoqkr0sgp5DyMOu0TSKUe5sxKE2dgM0ZfAJ8cMNEvT1SnmcggQ9l

SYSTEMIC COMORBIDITIES & POAG

 

It is often assumed that systemic co-morbidities, such as diabetes mellitus (DM) and hypertension (HT), are associated with a higher prevalence of glaucoma. However, there is also a suspicion that the number of patients with systemic disorders are diagnosed with glaucoma simply because of the increased approach of these patients to medical facilities and frequent eye checkups compared to normal, healthy populations, leading to higher rates of diagnosis. However, many landmark studies have definitely reported a significantly increased association of co-morbid systemic disorders and glaucoma.

A 5-year cohort study was performed by Zhou et al, to analyze the association between systemic comorbidity burden and glaucoma progression. [1] The comorbidity burden was measured by the age-adjusted Charlson Comorbidity Index (age-CCI) among patients attending the Cole Eye Institute in the USA. The Charlson Comorbidity Index (CCI) is a widely used assessment tool designed to predict long-term mortality. The objective of the study was to investigate whether higher CCI scores are associated with worse glaucoma outcomes, specifically progression to a more advanced stage of disease.

The retrospective cohort study included 11,863 patients aged 18 years of age or older diagnosed with primary open angle glaucoma, pre-glaucoma, or ocular hypertension between 2018 and 2024 with at least 5 years of follow-up.

The authors found that each one-point increase in the age-CCI score was associated with a 6% increase in the odds of progression from early-stage to moderate-stage glaucoma over the 5-year follow-up period (OR = 1.06, 95% CI: 1.04–1.09, P = 1.05×10−7). The odds of progression to moderate-stage glaucoma were higher in males compared with females (OR = 1.32, 95% CI: 1.17–1.49, P = 4.15×10−6). Compared with white patients, the odds of progression were higher for the black (OR = 2.09, 95% CI: 1.81–2.40, P < 2×10−16) and “other race” (OR = 1.81, 95% CI: 1.47–2.23, P = 1.52×10−8) cohorts. Patients with private insurance had lower odds of progression than those with public insurance (OR = 0.75, 95% CI: 0.65–0.86, P = 2.89×10−5), whereas patients with no listed insurance had no significant difference compared with those with public insurance. Patients with a history of one or more ophthalmic procedures or age related macular degeneration (AMD) diagnosis had higher odds of progression from early-stage to moderate- stage glaucoma than those without (OR = 1.33, 95% CI: 1.17–1.51, P = 1.84×10−5; OR = 1.34, 95% CI: 1.05–1.71, P = 0.017). Finally, each increase in prescribed glaucoma medication was associated with 88% increased odds of progression (95% CI: 1.80–1.97, P < 2×10−16).

The study also analyzed the progression from early-stage to severe-stage glaucoma. The odds of progression were higher for black (OR = 2.01, 95% CI: 1.61–2.49, P = 3.91×10−10) and “other race” (OR = 1.66, 95% CI: 1.17–2.31, P = 0.003) patients compared with white patients. Patients with private insurance had lower odds of progression than those with public insurance (OR = 0.68, 95% CI: 0.55–0.85, P = 0.001), while patients with no listed insurance had no significant difference compared with those with public insurance. Patients with a history of one or more ophthalmic procedures had higher odds than those without (OR = 1.81, 95% CI: 1.49–2.19, P = 1.54×10−9). AMD and RD diagnosis were associated with increased odds of progression from early-stage to severe-stage glaucoma (OR = 1.62, 95% CI: 1.13–2.26, P = 0.006; OR = 2.50, 95% CI: 1.57–3.85, P = 6.19×10−5). Finally, each additional prescribed glaucoma medication was associated with 90% increased odds of progression (OR = 1.90, 95% CI: 1.80–2.00, P < 2×10−16).

Another study was performed by Lin & colleagues, to compare the comorbid conditions between open-angle glaucoma patients and a control cohort. [2] The study group comprised of 76673 POAG patients, while the comparison group comprised of 230019 subjects matched to the study cohort. The data were collected retrospectively from the Taiwan National Health Insurance Research Database. In total, 31 medical comorbidities were selected based mainly on the Elixhauser Comorbidity Index.

More than half (50.5%) of the OAG patients had HT, and more than 30% had hyperlipidemia or DM (30.5% and 30.2%, respectively). The prevalence of 28 of 31 comorbidities were significantly higher for OAG patients than subjects without glaucoma after adjusting for age, gender, urbanization level, and monthly income. The adjusted odds ratio was more than 1.50 for hypertension, hyperlipidemia, systemic lupus erythematosus, diabetes, hypothyroidism, fluid and electrolyte disorders, depression, and psychosis.

However, a study by Motsko et al, did not find any association between glaucoma and hypothyroidism. [3]

A cross-sectional study of all glaucoma patients attending King AbdulAziz Medical City in Saudi Arabia was performed by Talaat et al, to identify the comorbidities in the patients.[4] A total of 283 patients met the inclusion criteria. 61% of their sample had hypertension, which was much higher than other reported studies from the region. Two mechanisms are postulated to explain the relationship between hypertension and open-angle glaucoma. The first is that increased arterial pressure will cause hardening and atherosclerotic changes in the retinal vasculature with subsequent arteriolar narrowing and elevated resistance, which eventually compromises the adequacy of perfusion to the optic disc. The other mechanism is related to the use of medications to lower blood pressure that might trigger episodes of systemic hypotension, which results in transient reductions in ocular blood supply.

58% individuals had DM. The mechanism by which DM is linked to glaucoma is believed to arise from impaired autoregulation of retinal and elevated predilection of retinal ganglion cells to programmed cell death.

Dyslipidemia was seen in approximately 33.6% of the sample. This finding is similar to other global studies but higher than local reports. there are reports of increased risk of glaucoma in patients taking high doses of statin medications.

Diabetes mellitus is not a well understood risk factor and its association to IOP or POAG is still controversial.[5] The epidemiological studies remain inconclusive, but some experimental studies have attempted to explain the biochemical mechanisms that link both the diseases. Neurodegenerative mechanisms cause an additional ganglion cell loss in glaucoma patients with DM. Therefore, the already vulnerable ganglion cells in glaucoma eyes come under additional stress in hyperglycemic conditions.

Large population studies, such as the Beaver Dam study, Rotterdam study and the Blue Mountains Eye study have shown an association between DM and higher IOP or development of POAG. Similarly, Amstrong’s analysis of the incidence of glaucoma in diabetes mellitus and a comparison with the incidence of glaucoma in the general population showed two to three times higher incidence of elevated IOP and POAG incidence in diabetes patients.[6] A recent meta-analysis of 47 studies by Zhao and colleagues reported a pooled relative risk of glaucoma of 1.48 in patients with diabetes compared to those without diabetes. [7]

The relationship between blood pressure (BP) and the incidence of glaucoma is still being debated. Some studies report that there is no correlation between systemic BP with IOP and the incidence of glaucoma. Even several other studies reported that in younger patients, HTN gave a protective effect by increasing the ocular perfusion pressure. However, some epidemiological studies have reported that an increase in systemic BP is associated with a slight increase in IOP. This is because the increase in BP increases episcleral venous pressure so that the aqueous outflow will decrease, causing a proportional increase in IOP.

A meta-analysis showed that individuals with systemic HTN had a significantly 1.71-fold risk of developing glaucoma compared with non-hypertensive individuals (1.71 (95% CI 1.58 to 1.85)). [8]

High BP can increase IOP through two mechanisms. First, an increase in the production of aqueous humor, which is caused by an increase in capillary pressure in the ciliary body, thereby increasing the intravascular pressure and IOP gradient; second, decreasing the outflow of aqueous humor due to an increase in episcleral venous pressure.

In conclusion, most systemic co-morbidities increase the risk for POAG and such patients should be monitored closely for the development/progression of glaucoma.

REFERENCES:

[1] Zhou, M. Y., Reed, H., Singh, R. P., Talcott, K. E., & Li, A. (2026). Association Between Systemic Comorbidity Burden and Glaucoma Progression: A 5-Year Cohort Study. Journal of Glaucoma, 35(6), 386–392.

[2] Lin HC, Chien CW, Hu CC, Ho JD. Comparison of comorbid conditions between open-angle glaucoma patients and a control cohort: a case-control study. Ophthalmology. 2010 Nov;117(11):2088-95.

[3] Motsko SP, Jones JK. Is there an association between hypothyroidism and open-angle glaucoma in an elderly population? An epidemiologic study. Ophthalmology. 2008 Sep;115(9):1581-4.

[4] Talaat K, Fathi OT, Alamoudi SM, Alzahrani MG, Mukhtar RM, Khan MA. Types of Glaucoma and Associated Comorbidities Among Patients at King Abdulaziz Medical City, Jeddah. Cureus. 2021 Jun 10;13(6):e15574.

[5] Costa L, Cunha JP, Amado D, Pinto LA, Ferreira J. Diabetes Mellitus as a Risk Factor in Glaucoma's Physiopathology and Surgical Survival Time: A Literature Review. J Curr Glaucoma Pract. 2015 Sep-Dec;9(3):81-5.

[6] Armstrong JR, Daily RK, Dobson HL, Girard LJ. The incidence of glaucoma in diabetes mellitus. A comparison with the incidence of glaucoma in the general population. Am J Ophthalmol 1960 Jul;50:55-63.

[7] Zhao D, Cho J, Kim MH, et al. Diabetes, fasting glucose, and the risk of glaucoma: a meta-analysis. Ophthalmology. 2015; 122:72–8.

[8] Nislawati R, Taufik Fadillah Zainal A, Ismail A, et al. Role of hypertension as a risk factor for open-angle glaucoma:a systematic review and meta-analysis. BMJ Open Ophthalmology 2021;6:e000798. doi:10.1136/bmjophth-2021-000798.

HIGH MYOPIA AND POAG (By DR. NEHA YADAV)

GUEST AUTHOR

DR. NEHA YADAV

ALIGARH

INDIA

Dr. Neha Yadav is a Consultant Ophthalmologist at Shree Bhagwandas Hospital, with a keen interest in glaucoma and comprehensive eye care. She is committed to early diagnosis, appropriate management, and patient education to help prevent avoidable vision loss.

This article is from a recent talk presented by Dr. Neha at the Myopia Conclave of the Aligarh Ophthalmological Society.

GINSENG EXOSOMES FOR GLAUCOMA

Chronic neuroinflammation is being recognized as a key etiopathological factor in the development of IOP-independent degeneration of retinal ganglion cells (RGCs) in glaucoma. Recent studies have highlighted neuroinflammation as a central pathological process driving RGC damage and disease progression.

Chronic low-grade retinal inflammation in glaucoma activates microglia, recruits peripheral immune cells and induces sustained release of pro-inflammatory cytokines, forming a vicious cycle of inflammation-oxidative stress-cell death that exacerbates neuronal injury.

As resident immune cells in the retina, microglia play a dual role in maintaining retinal homeostasis and responding to stress. Their dynamic functional state critically influences neuronal activities. Under pathological stimuli such as elevated IOP, ischemia, hypoxia or metabolic stress, microglia polarize from a resting state toward the pro- inflammatory M1 phenotype, releasing tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase and excessive reactive oxygen species (ROS), directly inducing RGC apoptosis.

Importantly, even after IOP normalization, persistently activated M1 microglia maintain an inflammatory environment, driving irreversible neurodegeneration.

Therefore, targeted modulation of microglial polarization has been considered a promising strategy for neuroprotection in glaucoma. However, safe, sustained and precise neuroprotective modulation of the retinal inflammatory microenvironment remains a significant challenge.

Plant-derived exosomes have recently emerged as natural nanovesicles with broad therapeutic potential due to their wide availability, excellent biocompatibility, relatively low production cost and capacity to carry diverse bioactive molecules, including nucleic acids, proteins, lipids and plant-specific metabolites.

Ginseng (Panax ginseng), a traditional medicinal herb, contains active compounds such as ginsenosides, polysaccharides and miRNAs known for their anti-inflammatory, antioxidative and immunomodulatory properties.

Scientists have developed an injectable fibrin gel delivery system loaded with ginseng-derived exosomes (GE-fibrin gel, GE-gel) to modulate microglial polarization, reduce retinal inflammation and promote RGC survival.

Fibrin based hygrogel delivery system of GE

In vitro, GE showed strong antioxidant and anti-apoptotic effects by getting rid of reactive oxygen species caused by oxidative stress and lowering apoptosis in R28 cells. Both GE and GE-gel stopped lipopolysaccharide from causing pro-inflammatory M1 polarization of microglia and increased anti-inflammatory M2 phenotypic change.

Intravitreal injection of GE-gel suppressed pro-inflammatory microglial activation, diminished neuroinflammation and improved the survival of RGCs in a chronic ocular hypertension rat model.

The study also showed that GE-gel could promote microglial polarization, change the immune environment in the retina and protect RGCs functionally over the long term. This approach may hopefully provide promising solutions for rapid and effective glaucoma therapy.

REFERENCE:

Zhou D, Tan D, Peng X, Fang C, Yu Y, Iqbal H, Zhang J, Fu L, Tang L, Zhou X, Zhang X, Xiao R, Zhu W, Yue L, Liang Y. Ginseng-derived exosomes loaded in fibrin gel promote retinal ganglion cell survival in glaucoma by exerting anti-inflammatory effects through modulating microglial polarization. Regen Biomater. 2026 Jul 10;13:rbag146. doi: 10.1093/rb/rbag146. PMID: 42534522; PMCID: PMC13420499. 

STEM CELL THERAPY

Stem cells are immature, uncommitted cell types that possess the abilities to:

• Self-renew indefinitely by symmetric cell division;
• Undergo asymmetric cell division also, generating another stem cell and a daughter cell capable of differentiating into multiple mature cell types.

By definition, a cell’s level of lineage commitment is inversely related to its potency. Pluripotent stem cells are capable of generating all cell types in the developing and adult body (embryonic stem [ES] and induced pluripotent stem [iPS] cells are two examples), while multipotent somatic stem cells are committed to a certain developmental lineage. During differentiation, stem cells undergo lineage commitment and lose their self-renewal capacity, thereby becoming progenitor cell that are further restricted in potency. Progenitor cells undergo limited proliferation prior to terminal differentiation to yield a mature cell type. A variety of distinct stem and progenitor cell classes exist, each with particular characteristics that make them attractive for certain potential therapeutic purposes. 

Stem cell transplantation therapy is of clinical interest because of its potential to treat degenerative conditions that are currently incurable (although in some cases manageable), such as glaucoma. 

There are at least two mechanisms by which stem cell transplantation might be applied to glaucoma. 

The most significant, prospective therapeutic power of stem cells lies in their ability to generate new cells of many types and to effect tissue regeneration. 

Thus, it is conceivable that stem cells may offer therapeutic hope for glaucoma via selective cell replacement of retinal glaucoma cells (RGCs) and optic nerve regeneration to restore function.

In addition, certain types of stem cells possess protective properties capable of alleviating disease progression and promoting survival of endogenous tissue. This is proposed to occur through a variety of mechanisms, some of which are cell or tissue specific. Ideally, RGC neuroprotection would serve as an adjunct with existing ocular hypotensive therapies to prevent progressive glaucomatous vision loss.

Transplantation of stem cells that secrete relatively high levels of neurotrophic factors (NTFs) is likely to be the most applicable short-term cell-based therapy for glaucoma.

Neural stem cells are reportedly capable of reducing CNS inflammation, thereby promoting functional recovery in a range of neurodegenerative diseases. If inflammation proves integral to glaucomatous RGC loss, then it is conceivable that the antiinflammatory properties of transplanted stem cells could confer benefit in glaucoma.

Other purported mediators of glaucomatous neurodegeneration include oxidative stress, vascular insufficiency and excitotoxicity. There is evidence that some stem cells secrete factors that could modulate these processes. 

While many stem cell transplantation studies have demonstrated histological and functional improvement in various neurodegenerative disease models, the exact mechanism(s) and pathway(s) underlying this effect remain, for the most part, elusive. It has been hypothesized that NTF secretion, anti-inflammatory modulation and many other processes play key roles, however, definitive mechanisms specific to RGC survival in glaucoma should be elucidated prior to clinical translation. This will facilitate full comprehension of a novel treatment, and may also reveal unappreciated mechanisms of RGC neuroprotection that may be amenable to manipulation via alternate intervention.

At present, it is unclear whether it may be more advantageous to transplant neural or retinal stem cells, RGC precursors (committed to an RGC fate but not yet fully differentiated) or mature RGCs for RGC replacement. 

TRADITIONAL CHINESE MEDICINE & GLAUCOMA

In Traditional Chinese Medicine (TCM), glaucoma is regarded as a systemic manifestation, classified under"Qingfeng Neizhang" (Green Wind Cataract/Glaucoma). 

TCM views glaucoma as an internal disharmony where stagnant energy (Qi) and poor blood flow fail to properly nourish the eyes, particularly affecting the Liver meridian. 

While Western medicine focuses primarily on lowering intraocular pressure (IOP), TCM serves as an adjunctive, neuroprotective therapy aimed at preserving retinal ganglion cells, improving microcirculation, and controlling oxidative stress.

TCM, as a medical system based on distinctive Chinese cultural theories and practices, has a long history of effective treatments and has been used for more than two thousand years. Glaucoma was first mentioned in the book Shennong Bencao Jing, in which it was described as "green wind glaucoma".

Since the Tang and Song Dynasty, ancient Chinese physicians have put forward unique views on glaucoma treatment. There are two main concepts regarding glaucoma: the green wind glaucoma, also known as “Lvfengneizhang” in ancient medical books, is similar to open-angle glaucoma; while the blue wind glaucoma, known as “Qingfengneizhang” is similar to angle-closure glaucoma. TCM ascribed the pathogenic factors of glaucoma to “excessive heat of liver-gallbladder (Gan Dan Shi Re)”.

Chinese medicine classifies ocular diseases as a hepatic disease, and often treats them with herbs that belong to the liver meridians. TCM generally exerts holistic effects owing to their multi-component and multi-target features, which have a unique advantage for glaucoma treatment.

TREATMENT:

Treatment of glaucoma with TCM is used as an adjunctive, supportive therapy alongside standard Western treatments to help protect the optic nerve and improve ocular blood flow, but it cannot replace conventional treatments for lowering IOP. 

Studies, including network pharmacology and clinical reviews, suggest that TCM may target mechanisms of neurodegeneration that conventional pressure-lowering therapies do not fully address.

Neuroprotection: Tonic herbs are studied for protecting Retinal Ganglion Cells (RGCs) from dying due to oxidative stress and excitotoxicity.

Microcirculation: Certain therapies help dilate blood vessels and improve blood flow to the optic nerve and retina.

Integrated Benefits: A meta-analysis published in PubMed indicated that combining standard surgery with TCM significantly improved visual field preservation and vision recovery compared to surgery alone.

HERBS FOR GLAUCOMA:

There are several specific herbs recommended in TCM for glaucoma management:

Ginkgo biloba: Widely recognized for improving ocular blood flow and providing antioxidant-driven neuroprotection.

Lycium barbarum (Goji Berry): Extensively researched for its ability to mitigate oxidative stress and protect RGCs from damage.

Erigeron breviscapus (Dandelion Flower): It supposedly expands the visual field and improves microcirculation in patients with controlled IOP.

Bujing Yishi Tablets: Used in hospital settings in China as a standard preparation to preserve visual function in patients whose IOP is already stable.

ACUPUNCTURE:

If the IOP is controlled within the target range, acupuncture treatment can be performed as an adjunct, especially for patients with obvious visual field damage. Acupuncture treatment contributes to maintain and improve vision as well as expand the field of vision.

Main points: Jingming, Chengqi point, fish waist acupuncture point, Fengchi acupoints; Matching acupoints: Temple, Baihui, Sibai, Hoku;

Main acupoints: Shangjing Ming, Retrobulbar acupoint, Tongzi Liao, Wangu; Matching acupoints: Temple, Waiguan, Ganyu, Shenyu;

Main acupoints: Xiajing Ming, Sibai, Sizhu Kong, Tianzhu; Matching acupoints: Temple, Binao, Zusan Li, Sanyin Jiao.

TCM is an ancient method of treatment and is undergoing modifications based on new knowledge and experience.

REFERENCES:

1. Yang Y, Ma QY, Yang Y, He YP, Ma CT, Li Q, Jin M, Chen W. Evidence-based practice guideline of Chinese herbal medicine for primary open-angle glaucoma (qingfeng -neizhang). Medicine (Baltimore). 2018 Mar;97(13):e0126.p doi: 10.1097/MD.0000000000010126. PMID: 29595636; PMCID: PMC5895393.
2. Qi SM, Zhang JT, Zhu HY, Wang Z, Li W. Review on potential effects of traditional Chinese medicine on glaucoma. J Ethnopharmacol. 2023 Mar 25;304:116063. doi: 10.1016/j.jep.2022.116063. Epub 2022 Dec 22. PMID: 36567037.

HyaGuard for Bleb Management

 

HyaGuard is a biodegradable, sub-conjunctival drug-delivery system designed for glaucoma filtration surgeries (such as trabeculectomies and microshunts).

It is a 3D-printed mesh structure surrounded by a hyaluronic acid hydrogel. It can be inserted into a sub-conjunctival pocket quickly during surgery. The insert is designed to fit current surgical protocols without needing additional tissue glue or sutures.

A preliminary study to assess the feasibility of the HyaGuard™ sub-conjunctival drug-delivery system in conjunction with the PRESERFLO™ MicroShunt (PFMS) was presented at the 2026 ARVO Annual Meeting, held in Denver, CO, May 3-7, 2026.

Methods : 5% w/w dexamethasone loaded HyaGuard™ units were fabricated by LEP Biomedical to create a 3D printed mesh surrounded by a hyaluronic acid hydrogel. HyaGuard™ units were freeze-dried and ethylene oxide sterilized prior to use. Commercially available PFMS were obtained from InnFocus Inc. and implanted in a sub-conjunctival pocket six female New Zealand white rabbits (3.0-3.9kg) using a standard procedure without the use of Mitomycin C. HyaGuard™ units were hydrated with balanced saline solution prior to implantation and were placed juxtaposed to the PFMS tube prior to the closure of the subconjunctival flap. Ophthalmic evaluations were performed at post operative days 1,3, 7, 14, 21 and 30. Ocular surface, bleb morphology, anterior chamber and intraocular pressures (IOP) were recorded. All procedures and time-point evaluations were conducted in accordance with the approved IACUC protocol.

Results : All six female rabbits appeared healthy throughout the study with no signs of distress, infection or intraocular inflammation. In the early post-operative period, grade I hyphema was observed (6/6) and central endothelial folds were observed (1/6) in one but resolved by week 2 without further complications. Histological analysis at 1 month confirmed the local tolerability of the HyaGuard™ units.

Despite not using Mitomycin C as an anti-fibrotic drug during the PFMS implant, blebs were observed in 2/6 rabbits (33%) after one month indicating the potential of the HyaGuard™ unit to maintain a bleb. Conjunctival swelling was minimal. ≥20% reductions in IOP were achieved up to D14 with a return to baseline by 1 month with a potential dose-response evident.

Conclusions : The HyaGuard™ implant was well tolerated in the rabbit eye in conjunction with the PFMS glaucoma drainage device for one-month showing normal bleb morphology and quiescent healing characteristics. This feasibility study showed that HyaGuard™ is likely safe to use with the PFMS and could potentially replace the use of intra-operative Mitomycin-C.

USE LINK HERE FOR THE FULL ARTICLE:

https://iovs.arvojournals.org/article.aspx?articleid=2813601

SEPETAPROST

Sepetaprost, developed by Santen and Ono Pharmaceuticals, is sold as Setaneo ophthalmic solution 0.002% as a once-daily eyedrop to reduce elevated intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). 

Sepetaprost is a novel investigative prodrug. It is a bicyclic prostaglandin derivative. The active form binds to and stimulates FP and EP3 receptors, promoting aqueous humor outflow and thereby lowering intraocular pressure (IOP). By activating both receptors, it increases the outflow of aqueous humor from the eye more effectively than traditional first-line prostaglandin analogs.

Clinical studies have shown that Sepetaprost 0.002% provides sustained IOP reduction consistently over 24-hours.

Comparisons with Timolol and Latanoprost have shown noninferior or superior efficacy of Sepetaprost. [1,2]

Conjunctival hyperemia (redness of the eye) is the most frequently reported ocular side effect. The majority of reported adverse reactions were considered mild to moderate, with no unexpected systemic safety concerns observed.

CLINICAL STUDIES 

1. The ANGEL-2 Study:

Involved 323 adult (≥18 years) participants (POAG, 68.4%; OHT, 31.6%) who were randomized 1:1 to receive either once-daily sepetaprost (n = 162) or twice-daily timolol (n = 161) in 1 eye for 3 months.

Results:

The primary endpoint, the noninferiority of sepetaprost to timolol in mean IOP reductions, was met. The upper limit of the 2-sided 95% CI for the between-group difference in mean IOP score was <1.0 mmHg at all 9 timepoints. Superiority of sepetaprost to timolol was observed at 4:00 pm in week 2, week 6, and month 3; IOP mean difference (standard error): −0.76 (0.302), –0.73 (0.328), and −0.95 (0.319), respectively (all P < 0.05). Overall, 23.6% of participants receiving sepetaprost and 21.3% receiving timolol experienced AEs. The most commonly reported ocular AE in both groups was conjunctival hyperemia (sepetaprost, 9.9%; timolol, 2.5%).

Conclusions:

Once-daily sepetaprost 0.002% was statistically noninferior to twice-daily timolol 0.5% for lowering IOP in participants with POAG or OHT. There were no unexpected safety concerns observed, and all AEs were mild or moderate in severity.

REFERENCE:

Wirta DL, El-Harazi SM, Tepedino ME, Bacharach J. Sepetaprost 0.002% Noninferiority vs. Timolol 0.5% in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: ANGEL-2. Ophthalmol Glaucoma. 2025 Jul-Aug;8(4):384-392. doi: 10.1016/j.ogla.2025.02.004. Epub 2025 Mar 4. PMID: 40043909.

2. In another study, 33 participants received treatment (sepetaprost, n = 17; latanoprost, n = 16). Mean 24-h IOP was numerically lower with sepetaprost vs. latanoprost at month 3 (- 0.88 mmHg; 95% confidence interval [CI] - 2.89, 1.14; not statistically significant at the 0.05 level [NS]). Mean change from baseline in IOP at month 3 ranged from - 5.63 to - 7.00 mmHg for sepetaprost and - 3.84 to - 6.66 mmHg for latanoprost. Lower nocturnal IOP was observed with sepetaprost vs. latanoprost at month 3 (- 1.61 mmHg difference; 95% CI - 4.05, 0.83; not statistically significant; however, the 90% CI was - 5.27, - 0.17 and therefore, nominal statistical significance was achieved at the 0.10 level). Mean difference between groups indicated similar, or numerically lower, IOP with sepetaprost at individual time points at week 6 and month 3. At 36 and 48 h following sepetaprost cessation, mean IOP was lower vs. baseline IOP at the same time points. AEs occurred in 13 (76.5%) vs. 11 (68.8%) participants treated with sepetaprost vs. latanoprost.

Conclusions: 

In participants with POAG or OHT, mean 24-h IOP and nocturnal IOP at month 3 were consistently numerically lower with sepetaprost vs. latanoprost. Safety profiles were similar between groups.

REFERENCE:

Konstas AG, Garhöfer G, Lübke J, Voykov B, Ropo A. A Study of 24-h Efficacy and Safety of Sepetaprost vs. Latanoprost in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension. Adv Ther. 2025 Aug;42(8):3810-3825. doi: 10.1007/s12325-025-03227-2. Epub 2025 Jun 10. PMID: 40493333; PMCID: PMC12313740.

CALIBREYE TGT SURGICAL SYSTEM

 

The Calibreye TGT Surgical System is intended to offer an adjustable solution to control IOP in patients with glaucoma.

The Calibreye is being evaluated as an Investigative Device Exemption (IDE) device, under the ADAPT trial. The first patient for the trial was recently enrolled by Myra Vision, the company involved in the manufacture of the device.

The ADAPT trial is a prospective, multicenter, nonrandomized open-label study that will enroll up to 70 refractory glaucoma patients with a 12-month primary effectiveness endpoint. The clinical investigation will evaluate the safety and effectiveness of the company’s titratable glaucoma therapy system, designed to optimize IOP reduction in patients undergoing glaucoma surgery. Once implanted, the Calibreye aqueous shunt is designed to enable slit lamp-based outflow adjustments as individual patient requirements evolve over time.

The Calibreye has the following specifications:

10.0 x 1.6–mm overall dimensions intended to provide posterior bleb formation to increase aqueous drainage.

Low profile (0.30 mm thick) to help maximize patient comfort and minimize erosion risk.

Suture eyelets for a secure shunt placement.

Visual indication for confirmation of channel settings.

Uses materials with well-known ophthalmic biocompatibility:

Silicone

• Hydrophobic properties help reduce protein binding to minimize cellular adhesion.
• Flexible and stable polymer with minimal biodegradation in vivo.
• Hyperemia is milder than with stainless steel
• Inflammatory response is milder than with polypropylene used in other devices.

Valve components composed of nitinol, a material with a proven history of use in ocular applications.

A multi-center international feasibility study involving Calibreye implantation, enrolled 43 patients with moderate to late-stage disease, of which 33 patients had greater than 3 months of follow-up, at four sites in three countries. 

The 3-month clinical trial results presented demonstrated:

1. 44.9% intraocular pressure (IOP) reduction compared to baseline, with an average IOP of 12.1 mmHg.
2. 88% of patients were medication-free, with 100% of patients on less than or equal to the number of meds at baseline.
3. Over 96% mean medication reduction compared to baseline, equating to a mean reduction of over 3 medications per patient.
4. No patients required bleb needling procedures.
5. 100% of devices implanted successfully, 100% of titrations completed successfully with an average of 2.2 titrations per patient.