NERVE GROWTH FACTORS FOR TREATMENT OF GLAUCOMA

 

• Neurotrophin-based therapies, such as recombinant human nerve growth factor (rhNGF), are promising candidates for non-IOP based treatments by directly targeting neuronal survival mechanisms.

• Nerve Growth Factor (NGF), is an insulin-like protein derived from its precursor proNGF through extracellular proteolytic cleavage.
• NGF exerts its biological actions via two receptors: the high-affinity receptor tropomyosin receptor kinase A (TrkA) and the low affinity p75 neurotrophic receptor (p75NTR).
• Studies show that purified NGF is a pleiotropic factor targeting a wide range of cell types in the central nervous system as well as non-neuronal cells throughout the body.
• Vecchiotti et al, have evaluated the therapeutic efficacy of intravitreal rhNGF in a spontaneous genetic model of pigmentary glaucoma.
• An improvement in visual acuity was observed in rhNGF-treated mice compared to vehicle-treated mice suggesting a protective effect of rhNGF against visual loss already noticeable in the early stages of disease and maintained in fully developed glaucoma.
• Results demonstrate that a single intravitreal rhNGF administration not only preserves retinal integrity and increases RGC survival, thus improving visual function and electrophysiological responses in glaucomatous mice, but also modulates key molecular pathways involved in oxidative stress, metabolism and neuroinflammation.
• Immunohistochemistry (IHC)-based retinal layer thickness measurements showed mice treated with rhNGF exhibited a significant increase in total retinal thickness compared to vehicle-treated mice. Specifically, rhNGF treatment prevented thinning of the RNFL/ganglion cell layer (GCL), suggesting that rhNGF could counteract RGC loss.
• Additionally, the rhNGF-treated group showed increased thickness in the inner nuclear layer (INL) and outer plexiform layer compared to vehicle-treated mice. The inner plexiform layer (IPL) was also thicker in the rhNGF group compared to controls (p = 0.054), while the outer nuclear layer and photoreceptor layer (PL) were unaffected by treatment.
• The drug-treated mice also showed an increased number of RGCs compared to vehicle-treated mice.
• rhNGF inhibited the activation of the apoptotic pathway. Western blot analysis of retinal lysates revealed that rhNGF treatment strongly downregulated pro-apoptotic JNK signaling and upregulated the expression of genes known to be associated with RGC viability.
• Treatment with the neurotrophin resulted in an upregulation of gene signatures for oxidative phosphorylation, mitochondrial respiratory chain complex assembly, and mitochondrial matrix in rhNGF-treated animals compared to controls. Conversely, key glycolytic genes such as Pfkfb2, Pgam1, and Pgk1 were downregulated in the drug-treated group, suggesting that rhNGF treatment may induce a metabolic shift towards oxidative phosphorylation (OXPHOS), indicative of improved retinal cell functionality.
• rhNGF treatment downregulated the expression of oxidative stress markers such as Nos1 and Nos3, mainly expressed in GCL and RPE layers, respectively, while mRNA levels of Nos2, associated with astrocytes and microglia, remained unaffected.
• The Nrf2 gene signature and protein levels were enriched in rhNGF-treated mice compared to controls, indicating that rhNGF-dependent activation of Nrf2 could help to maintain the health of RGCs by upregulating antioxidant defences, thus preventing cell death.
• Immunohistochemical analysis showed a strong decrease in the expression of IBA1 and GFAP, two well-known markers of reactive gliosis, in the retina of rhNGF-treated mice compared to vehicle-treated mice.
• Treated mice had decreased levels of the pro-inflammatory cytokines IL-1β, TNFα, and IL-6, and an upregulation of the anti-inflammatory cytokine IL-4.
• Notably, these protective effects are sustained over time despite a single administration, highlighting the potential of rhNGF to induce durable neuroprotective responses in the glaucomatous retina.

• These findings highlight the potential of rhNGF as a multifactorial neuroprotective therapeutic strategy for glaucoma, providing cytoprotective, antioxidant and anti-inflammatory benefits.

REFERENCE:

Vecchiotti, D., Di Vito Nolfi, M., Compagnoni, C. et al. rhNGF shows neuroprotective efficacy by counteracting oxidative stress and neuroinflammation in a glaucoma mouse model. Cell Death Discov. (2026). https://doi.org/10.1038/s41420-026-03345-y

PREMIUM IOL IMPLANTATION IN GLAUCOMA PATIENTS

 

Premium intraocular lenses (IOLs), including multifocal, extended depth-of-focus (EDOF), and light adjustable lenses (LALs) are being increasingly used to reduce spectacle dependence after cataract surgery. However, their use in glaucoma patients remains controversial due to concerns that reduced contrast sensitivity and pre-existing visual field loss limits functional benefits from these optics.

A systematic review to evaluate the use of premium IOLs in glaucoma was performed by Hong and colleagues. Twelve studies were included in the final review to analyze the post-operative outcomes.

The studies demonstrated high spectacle independence for distance and good patient satisfaction in glaucomatous eyes, with positive outcomes also in post-operative visual acuity, residual astigmatism, and contrast sensitivity.

Considerations in patient selection include anatomical and functional factors, such as the type and severity of glaucomatous visual field defects, glaucoma subtype, presence of ocular surface disease, ocular changes after glaucoma surgery, and the reliability of disease monitoring, all of which may be affected by, or influence, the outcomes of premium IOL implantation in glaucoma patients. (1)

Another recent single-center, retrospective observational study with cross-sectional survey analysis included glaucoma patients who underwent bilateral cataract surgery with implantation of multifocal, EDOF, or LAL IOLs with concurrent MIGS from 2020 to 2025.

Seventy-nine patients (Multifocal n=43, EDOF n=24, LAL n=12) were included. All groups demonstrated significant postoperative improvement in distance visual acuity and reduction in IOP and glaucoma medication burden.

Adjusted IOP trajectories and most recent IOP were similar between groups. Distance visual acuity outcomes were similar between groups after adjustment for baseline glaucoma severity. Near visual acuity favored multifocal IOLs, while LAL demonstrated the highest spectacle dependence. Dysphotopsias were more frequent with multifocal lenses and lowest in LAL.

Satisfaction was high across all groups, with predicted probabilities of being “very” or “somewhat satisfied” of 94% (multifocal), 88% (EDOF), and 87% (LAL). (2)

10-2 VISUAL FIELD CHANGES AND IOL SELECTION:

An important consideration for choosing the appropriate IOL is the 10-2 visual field analysis. A 10-2 visual field defect indicates central or paracentral glaucomatous damage, which generally makes standard multifocal IOLs (which split light and reduce contrast sensitivity) a high-risk choice.

Multifocal lenses worsen contrast sensitivity, which is already compromised when central visual field points are lost. Standard 24-2 perimetry often misses critical central damage that a 10-2 visual field assessment uncovers, making it vital for safe premium intraocular lens selection in glaucoma patients.

The 24-2 samples the central visual field with relatively widely-spaced points; the 10-2 samples the central 10 degrees with denser coverage. When both tests are performed in the same patient, the 10-2 detects abnormalities in nearly as many hemifields as the 24-2, including in eyes with normal 24-2 fields. The pattern of these defects is consistent with a model of macular damage that the 24-2 cannot adequately resolve.

The anatomical features of the macula have to be considered also, particularly it’s susceptibility in early glaucoma. Optical coherence tomography (OCT) of the retinal nerve fibre layer and ganglion cell complex demonstrates that glaucomatous damage frequently involves the macular region early in the disease, with thinning concentrated inferiorly and corresponding visual field defects close to fixation in the upper field. A 24-2 with full mean deviation does not exclude this damage.

For premium IOL candidacy, the threshold is straightforward. Published series of EDOF IOL outcomes in early glaucoma have used selection criteria that explicitly exclude fixation-threatening defects. The 10-2 is the test that confirms or refutes that criterion.

Patients are reassured by structured numbers. MD better than -3 dB sounds reassuring. It does not, by itself, exclude central involvement. A clean 10-2, not just a clean 24-2, should be part of the candidacy assessment whenever there is any suggestion that the macula may be involved. (3)

CONCLUSION:

In appropriately selected glaucoma patients undergoing cataract surgery multifocal, EDOF, and LAL IOLs provide comparable visual outcomes, excellent IOP control, and high satisfaction. Differences in spectacle dependence and dysphotopsia support individualized IOL selection. Involvement of 10-2 (central) fields indicate a preference for monofocal lenses.

REFERENCES:

1. Hong ASY, Ang BCH, Dorairaj E, Dorairaj S. Premium Intraocular Lenses in Glaucoma-A Systematic Review. Bioengineering (Basel). 2023 Aug 22;10(9):993. doi: 10.3390/bioengineering10090993. PMID: 37760095; PMCID: PMC10525961.
2. Wolsky, J., Jemiyo, C., & Greenwood, M. (2026). Clinical and Patient-Reported Outcomes of Premium Intraocular Lenses in Glaucoma Patients Undergoing Combined Cataract and Minimally Invasive Glaucoma Surgery. Clinical Ophthalmology, 20. https://doi.org/10.2147/OPTH.S628605
3. https://bluefinvision.com/knowledge-base/topics/diagnostics-testing/why-a-10-2-visual-field-matters-before-premium-lens-surgery/

BIMATOPROST VS TRAVOPROST SUSTAINED-RELEASE IMPLANTS

This review and analysis was performed to evaluate the efficacy and safety of sustained-release intracameral prostaglandin analog implants, including bimatoprost (Durysta) and travoprost (iDose TR), in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

A systematic review and pooled quantitative analysis were performed according to PRISMA guidelines. PubMed, Scopus, Embase, and Google Scholar were searched for studies published between 2020 and 2025 evaluating sustained-release intracameral prostaglandin implants. Randomized and non-randomized studies reporting intraocular pressure (IOP) and safety outcomes were included.

Six studies comprising 1,047 eyes met inclusion criteria. Bimatoprost implants (10 µg and 15 µg) achieved mean IOP reductions of 6.1–6.7 mmHg at 12 months, whereas pooled slow-eluting travoprost implant data demonstrated reductions ranging from 5.5 to 7.75 mmHg depending on study design and follow-up duration. 

Subgroup analysis demonstrated comparable efficacy between travoprost and bimatoprost implants at 3 months; however, at 12 months, travoprost efficacy was lower than the 15 µg bimatoprost implant while remaining comparable to the 10 µg implant. 

Most adverse events were mild and transient. Corneal endothelial cell loss occurred in a dose-dependent manner with repeated bimatoprost administrations, particularly with the 15 µg implant, whereas no significant endothelial cell loss was reported with travoprost implants. Both implants substantially reduced topical medication burden.

The study concluded that sustained-release intracameral prostaglandin implants provide durable IOP reduction while decreasing dependence on topical therapy. 

REFERENCE:

Chopra AL, Siringoringo C, Siu S, Francis B, Mahdavi Fard A. Sustained-Release Intracameral Prostaglandin Analog Implants for Glaucoma: Comparative Review and Meta-Analysis of Bimatoprost and Travoprost Delivery Systems. J Ocul Pharmacol Ther. 2026 Aug 3:10807683261474828. doi: 10.1177/10807683261474828. Epub ahead of print. PMID: 42544565.

DOES LATANOPROST EXACERBATE RGC LOSS?

 

INTRODUCTION:

Parvin Niknam and colleagues from the Mayo Clinic, USA, have compared diazoxide (DZ), an ATP-sensitive potassium channel opener and latanoprost free acid (LFA), the active metabolite of the prostaglandin analogue latanoprost, on IOP, retinal ganglion cell (RGC) density, retinal morphology, and glial cell activation in the DBA/2J mouse model of pigment dispersion glaucoma.

Therapeutics that open ATP-sensitive potassium (KATP) channels, such as diazoxide (7-chloro−3-methyl-4H−1,2,4-benzothiadiazine 1,1-dioxide; DZ), are an emerging strategy for IOP reduction and direct neuroprotection through multiple mechanisms.

DZ is an FDA approved agent for treating hyperinsulinism and hyperphagia in Prader-Willi Syndrome, and to treat systemic hypertension.

METHODOLOGY:

DBA/2J mice age 4 months received daily topical applications of DZ (5 mM) or LFA (0.1 mM) in one eye, while the fellow eye received the vehicle. IOP was measured prior to treatment and twice weekly throughout the 23-week treatment period. Immunofluorescence staining was used to quantify RGC density with RNA binding protein with multiple splicing (RBPMS) and glial cell activation as a measure of neuroinflammation with glial fibrillary acidic protein (GFAP). Hematoxylin and eosin staining was used to evaluate retinal morphology.

RESULTS:

The study was significant in that it found that IOP was reduced by both DZ (30%) and LFA (24%) for a portion of the experimental period. However, importantly, DZ did not alter RGC survival, reactive gliosis, or RGC morphology. Conversely, LFA treatment was associated with a significant reduction in RGCs, an increase in reactive gliosis, and altered RGC morphology characteristic of cell death.

CONCLUSION:

The study concluded that DZ lowered IOP without notable retinal side effects. In contrast, LFA reduced IOP but was associated with enhanced RGC neurodegeneration and increased neuroinflammation.

The findings suggest that prostaglandin analog therapy might carry risks of enhanced neurodegeneration in eyes with pre-existing pro-inflammatory microenvironments, though further research is needed outside the DBA/2J strain.

REFERENCE:

Parvin Niknam, Mohammed E. Omer, Kjersten J. Anderson, Tommy A. Rinkoski, Uttio Roy Chowdhury, Gavin W. Roddy. Daily topical latanoprost free acid exacerbates retinal ganglion cell degeneration in the DBA/2J mouse model of pigment dispersion glaucoma. Prostaglandins & Other Lipid Mediators, Volume 186, 2026, 107101, ISSN 1098-8823. https://doi.org/10.1016/j.prostaglandins.2026.107101.