SITAGLIPTIN

The underlying molecular mechanisms involved in retinal ganglion cell (RGC) apoptosis in glaucoma remain to be fully elucidated, but inflammation plays an important role. 

Studies have shown neuroprotective properties with Glucagon-Like Peptide (GLP-1) and GLP-1 receptor agonists (GLP-1RA).

GLP-1/GLP-1R are produced by the human retina and mRNA levels and protein content of GLP-1 were significantly lower in retinas from subjects with diabetes in comparison with normal individuals.

GLP-1 levels in the retina can be increased by two mechanisms. One, by topical administration of GLP-1, so that the agent reaches the retina. And two, by reducing the degradation of GLP-1. 

Degradation of GLP-1 occurs by catalytic activity of the enzyme dipeptidyl peptidase IV (DPP-IV). This enzyme is found in higher concentration in diabetic retinas.

Sitagliptin an inhibitor of DPP-IV, reduces the degradation of GLP-1 and thereby, increases its levels in the retina.

The main function of mature oligodendrocytes in the central nervous system is to generate myelin sheaths, which accelerate the conduction of nerve impulses and provide metabolic support for neuronal axons. In a dexamethasone induced glaucoma model, researchers found a significant loss of positive Oligo-2 cells compared to untreated controls (p < 0.05). However, Sitagliptin treatment prevented RGC and oligodendrocyte (OL) loss in the retina and optic nerve head (ONH).

In glaucomatous retina, three types of glial cells, astrocytes, microglia, and Müller cells, can become activated. Microglia and macroglia are the cell types involved in inflammatory responses within the retina. Under pathological conditions, these glial cells become reactive, lose their homeostatic functions of trophic and metabolic support, and gain neurotoxic properties that trigger inflammatory-mediated neurodegeneration. Sitagliptin is neuroprotective by reducing astroglial activation in the ONH and the retina. It also reduces microglial activation in the ONH.

Gamma-synuclein can be considered a member of the Bcl-2 apoptosis family, and its overexpression and accumulation in glaucomatous eyes has a role in the pathogenesis of glaucomatous neurodegeneration by facilitating the disintegration of neurofilament networks such as Neurofilament heavy subunit (NFH) by activating astrocyte phagocytosis in the ONH and inhibiting optic nerve regeneration. The loss and dephosphorylation of neurofilament deprives metabolic routes of essential substrates for axonal energetics, thereby increasing the susceptibility of axons to injury. 

The authors found that topical administration of sitagliptin inhibits the overexpression of both macro and microglial activation that occurs in the neuroretina and in the ONH. In glaucoma there is significant loss of NFH, which is prevented by topical administration of sitagliptin.

REFERENCE:

Bogdanov P, Duarri A, Sabater D, Canz MJ, Isla-Magrané H, Ramos H, Deàs-Just A, Simó R, Hernández C. Topical Administration of Sitagliptin Prevents Retinal Neurodegeneration in a Model of Glaucoma Induced by Dexamethasone. Int J Mol Sci. 2025 Dec 20;27(1):48. doi: 10.3390/ijms27010048. PMID: 41515932; PMCID: PMC12785737.

HYPOTONIC MACULOPATHY

Ocular hypotony may occur after ocular inflammation, trauma or surgery, especially glaucoma filtration surgery (GFS) with antifibrosis drugs. Postoperative hypotony may develop following retina, cataract, cornea and strabismus surgeries in addition to filtering surgery. 

Several definitions are used for describing ocular hypotony. A statistical or numerical definition is IOP below 6.5 mmHg, which is more than three standard deviations below the mean. An alternative clinical definition is IOP low enough to result in vision loss, although low IOP alone may not result in vision loss. Vision loss associated with low IOP is commonly caused by corneal edema, astigmatism, cystoid macular edema or maculopathy. The World Glaucoma Association considers hypotonic IOP one which causes clinical complications with a potential of visual disturbance. This is regarded as IOP ≤5 mmHg.

Hypotony maculopathy is characterized by a low IOP with associated fundus changes, including chorioretinal folds, optic nerve swelling and vascular tortuosity. The chorioretinal folds are most likely secondary to the collapse of the scleral wall. Wrinkling in the retina or thickening in the choroid may cause axial shortening of the eye, leading to hyperopia.

Disc swelling results from restricted axoplasmic flow, presumably from anterior bowing of the lamina cribrosa in the optic nerve. These findings may be less pronounced in eyes with advanced glaucoma because these eyes have fewer remaining axons that can swell. Clinically, patients may experience metamorphopsia or central vision loss, or they may be asymptomatic.

Hypotony maculopathy can occur with increased outflow of aqueous humor or, less often, with decreased aqueous production. Outflow can increase because of a wound leak, a scleral rupture, a cyclodialysis cleft, a retinal detachment or an overfiltering bleb—or, rarely, from a ciliochoroidal detachment. Decreased aqueous humor production may be secondary to uveitis, hypoperfusion of the ciliary body in ocular ischemia, or a ciliochoroidal detachment.

One of the most important risk factors for hypotony maculopathy is the use of antifibrosis drugs, especially mitomycin C, during GFS. Intraoperative use of MMC can lead to overfiltration or bleb leaks in the late postoperative period which may be associated with hypotony maculopathy. Higher concentrations and increased application times of antifibrosis agents not only may lead to excessive filtration but also may have a toxic effect on the ciliary body, thus leading to decreased aqueous humor production.

A retrospective study of other risk factors for hypotony maculopathy showed that young age, male gender and myopia increased the risk, whereas a history of diabetes and the presence of choroidal effusions decreased the risk.

Diagnosis of the condition is made by performing a Seidel's test which demonstrates aqueous leak from the bleb. Fundus examination reveals the characteristic retino-choroidal changes. Investigations such as B-scan and OCT will demonstrate other findings associated with hypotonic maculopathy such as thickening of the posterior sclera or choroid, and choroidal detachments or macular changes. Ultrasound biomicroscopy and intravenous fluorescein angiography help in identifying choroidal folds.

In treating hypotony maculopathy, the goal is to normalize IOP as soon as possible to prevent permanent retinal dysfunction and associated vision loss. However, IOP correction is not guaranteed to improved visual acuity, especially in cases of long-standing hypotony maculopathy.

Treatment of hypotonic maculopathy is aimed at the cause. Bleb leaks can be managed by scleral or bandage contact lenses, symblepheron ring, aqueous suppression, topical antibiotics like gentamicin which facilitates fibrosis and broad spectrum antibiotics to prevent infection, or suturing if conservative approach fails. Other options are autologous blood injection into the bleb, fibrin tissue glue, cyanoacrylate glue, argon laser application or direct suturing of the bleb, although these treatments seldom produce a longlasting solution. 

Late-onset bleb leaks that do not resolve spontaneously or with conservative measures often require surgical intervention. Amniotic membrane or autologous conjunctival grafts can be considered.

Hypotony maculopathy secondary to overfiltration may be managed by adding compression sutures to the elevated, overfiltering bleb. Autologous blood injection, in or around the bleb, may be helpful in some patients. During the early postop period, with an overfiltering bleb, anti-inflammatory medications may be rapidly tapered to facilitate episcleral scarring.

Preventive measures can be taken intraoperatively during GFS to reduce the risk of post-op hypotony maculopathy. There are three critical areas created during GFS that ensure smooth passage of aqueous humor. These are:

1) sclerostomy; 

2) scleral flap; and 

3) subepiscleral/subconjunctival areas. 

The above-mentioned intraoperative areas should be controlled meticulously to prevent the development of post-op hypotony. 

Multiple flap sutures should be placed, with additional sutures if aqueous flow is excessive. The conjunctiva should be closed with the use of tapered (vascular) needles to reduce suture track leaks. If possible, the conjunctival closure should incorporate Tenon’s capsule, whether by a two-layer or a one-layer method. Postoperatively, properly timed removal of releasable sutures or laser lysis of other sutures can decrease the precipitous reduction of IOP and the potential for hypotony maculopathy.

In cases of glaucoma drainage devices, intraoperative tube ligation is performed using absorbable sutures. These sutures usually absorb after 5 weeks and controlled IOP is seen. However, early absorption or opening of the suture causes over-filtration. Techniques such as blocking the tube ab interno or ligating the tube have been described.

Some authors recommend viscoelastic substance or perfluoropropane gas injection into the anterior chamber in conjunction with tube ligation. In case of failure, ab interno stent, tube shunt plate truncation and implant 

explantation are other surgical methods that can be considered.

PLURIPOTENT EPIGENETIC REGULATOR OBP-801

 

OBP-801 (also known as YM753) is a novel histone deacetylase (HDAC) inhibitor developed by Oncolys BioPharma for potential anticancer treatment, demonstrating effects like inducing cell death (apoptosis) and halting cancer cell growth in various cancers, including lung, breast, and brain tumors, often synergistically with other drugs, by interfering with HDAC enzymes crucial for cancer progression. It works by inhibiting HDACs, leading to gene expression changes that trigger cancer cell death.

OBP-801 has been studied in animal glaucoma models and found to improve the survival of filtering blebs.

Koga and colleagues have demonstrated the anti-fibrotic effect of OBP-801 (OBP) on filtering blebs in a rabbit glaucoma filtration surgery (GFS) model, as well as rabbit eyes which underwent PRESERFLO microshunt implantation surgery (PMS).

The second study involved 19 Japanese white rabbits that underwent PMS in the right eye, with those eyes divided into 3 groups: (1) intraoperative subconjunctival injection of 0.02% mitomycin-C (MMC) (n = 6), (2) postoperative instillation of 100 nM OBP eye drops (n = 7), or (3) a balanced salt solution (BSS) control (n = 6). 

Bleb morphology and IOP were monitored for 12 weeks postoperative, with the bleb tissues then undergoing evaluation of fibrosis and Western blot analysis. 

A lower postoperative IOP was maintained in the OBP-group eyes, and at 12 weeks postoperative, the IOP was significantly lower in that group than in the BSS and MMC groups (p < 0.01). 

OBP-treated eyes showed no adverse effects and reduced levels of alpha-smooth muscle actin and collagen deposition, thus suggesting that OBP is a promising candidate for improving surgical outcomes post PMS.

Yamamoto et al have also studied the effect of OBP in rabbit eyes with GFS. They found OBP treatment involving subconjunctival injection or eye drops showed no adverse effects, and reduced levels of α-SMA and collagen deposition at the surgical wound site. OBP maintained the long-lived bleb without scar formation, and IOP was lower at 30 postoperative days compared with the vehicle control group. These findings suggest that OBP is an effective and useful candidate low-molecular-weight agent for improving wound healing and surgical outcomes in a rabbit model of GFS.

REFERENCES:

1. Koga, Y., Ikushima, T., Hiramoto, N. et al. Pluripotent epigenetic regulator OBP-801 attenuates fibrosis and maintains lower intraocular pressure in a rabbit PRESERFLO MicroShunt surgery model. Sci Rep (2025). https://doi.org/10.1038/s41598-025-34244-4.
2. Yamamoto Y, Mukai A, Ikushima T, Urata Y, Kinoshita S, Hamuro J, Ueno M, Sotozono C. Pluripotent epigenetic regulator OBP-801 maintains filtering blebs in glaucoma filtration surgery model. Sci Rep. 2020 Dec 1;10(1):20936. doi: 10.1038/s41598-020-77811-7. PMID: 33262357; PMCID: PMC7708845.

ASSOCIATION OF BREAST CARCINOMA WITH GLAUCOMA

Glaucoma is a potentially blinding condition that can cause significant morbidity when vision is affected.

Breast carcinoma is the most common malignancy among females. The condition has significant mortality when associated with systemic metastases.

The two conditions, glaucoma and breast cancer, appear to have some association with each other.

However, there is a significant lack of notable studies or case reports detailing this association.

Our review, published in touchREVIEWS in Ophthalmology, is a significant addition to the current knowledge regarding association between breast cancer and glaucoma.

SEE LINK BELOW:

https://touchophthalmology.com/glaucoma/journal-articles/association-of-breast-carcinoma-with-glaucoma-a-review/

MMC INJECTION VS SPONGE

Trabeculectomy is the most common incisional surgery for glaucoma. In the early years, the post-trabeculectomy failure rate was up to 20%-90%. However, with the introduction of antimetabolites such as 5-fluorouracil (5-FU) and mitomycin C (MMC), which act by inhibiting scar formation and tissue remodeling, surgical success rates have substantially improved. Previous meta-analysis comparing 5-FU and MMC demonstrated that MMC was associated with better clinical outcomes, including lower mean IOP and higher rates of complete and qualified success.

Traditionally, MMC has been applied using sponges. However, there has been a trend in recent years towards intraoperative injection.

Some advantages of injection are no risk of accidental retention, which can lead to infection or necrosis, reduction in surgical time, and accuracy of the injected dose.

A systematic review and meta-analysis was performed to compare the efficacy and safety of intraoperative injection of mitomycin C (MMC) versus conventional MMC-soaked sponges in patients undergoing trabeculectomy. Pubmed, Cochrane, and Embase were searched for studies published until December 2023 comparing injection and sponge techniques during trabeculectomy.

The pooled analyses of 11 studies revealed that the incidence of complete surgical success was higher in the injection group (OR=1.79; 95% CI: 1.33–2.40; complete success). In 10 trials, the rate of qualified success was found to be greater in the sponge group (OR=0.61; 95% CI: 0.42–0.89; qualified success). In addition, 8 trials demonstrated no significant difference between groups in the incidence of treatment failure (OR=0.87; 95% CI: 0.60–1.26; treatment failure).

The dose of MMC varied from 0.1 to 0.4 mg/mL.

The main findings in the overall analyzed population were: (1) lower mean IOP at 6 months in the injection group; (2) no significant difference between groups in mean IOP at 12 months; (3) no significant difference between groups in the number of antiglaucoma medications at 6 months and ≥12 months; (4) higher rate of complete success in the injection group; and (5) no significant difference between the groups in the incidence of postoperative complications.

The study concluded that, intraoperative MMC injection had a greater rate of complete surgical success and reduction in the number of medications. However, there was no significant difference in mean IOP at 12 months between groups. MMC injection was as safe as sponge application in trabeculectomy.

REFERENCE:

Gaban, Natália MD*; Pelison, Gustavo MD*; Binotti, William W. MD†; Taranta, Luiz F. MD*; Krishnan, Chandrasekharan MD†. Intraoperative Injection Versus Sponge-Applied Mitomycin C During Trabeculectomy In Glaucoma: A Systematic Review and Meta-Analysis. Journal of Glaucoma 34(12):p 1003-1016, December 2025. | DOI: 10.1097/IJG.0000000000002624 

AHMED GLAUCOMA VALVE IN KPro PATIENTS

Postoperative glaucoma following keratoprosthesis (artificial cornea) implantation is a challenge, as it is often refractory to conventional management.

A retrospective chart review by Minh T Nguyen, found that eyes with a type 1 keratoprosthesis (KPro) appear to have relatively good intermediate-term glaucoma management with the Ahmed glaucoma valve (AGV), though some tube-related complications were seen.

Study Design

This was a retrospective study involving 38 patients (38 eyes) with a type 1 KPro who underwent AGV placement for IOP control between 2009–2021 at a single hospital in India. All eyes received AGV implants either at the time of or following type 1 KPro implantation, with the drainage tubes predominantly placed in the ciliary sulcus.

Outcomes

• The median follow-up duration was 30.5 months (range 6.5–30.5 months). 
• Following AGV implantation, median IOP significantly declined from 30.4 mm Hg to 13.5 mm Hg.
• The average number of glaucoma medications decreased from 3.4 to 1.7.
• BCVA remained stable. 
• Humphrey visual field analysis showed progression in 10 eyes (26.3%), with an overall decrease in mean deviation from –13.5 to –26 dB. 
• Postoperative complications occurred in 8 eyes (21%), including 7 tube-related complications that underwent successful surgical repair; there were no instances of implant extrusion or endophthalmitis.

Limitations

Similar to other retrospective chart reviews, this study lacked a control group for direct comparison. Additionally, many patients had relatively short follow-up, as brief as 6.5 months, which may not have been sufficient to assess late-onset complications such as implant extrusion or endophthalmitis. The limited follow-up duration also makes it difficult to reliably assess long-term glaucoma stability.

Clinical Significance

This study supports the integration of glaucoma drainage device implantation, particularly the AGV, in eyes with a type 1 KPro to prevent the onset or progression of glaucoma, one of the most serious vision-threatening complications associated with KPro. However, tube-related issues can still occur, highlighting the need for careful, long-term monitoring to preserve visual outcomes.