COLLOIDAL DRUG AGGREGATES IN GLAUCOMA

Hollow nanoparticle and core-shell nanoparticle eye drops improve ocular retention and sustain release of drugs for up to 7 days. These strategies use either non-biodegradable materials, which can accumulate, or degradable materials with acidic degradation products that can trigger an inflammatory response.

Colloidal drug aggregates (CDAs) are self-assembled, amorphous, drug-rich nanoparticles.

CDAs can achieve high-loading (typically >70%) drug formulations by stabilizing them with small amounts of excipients, such as polymers, proteins, lipids,indocyanine dyes or other small-molecule aggregators. This contrasts with the typical <10% drug loading in nanoparticle formulations. Although CDAs have been studied for oral and intravenous administration, their use in local delivery had not been investigated until this study.

Incorporating timolol CDAs into a new hyaluronan (HA)-oxime hydrogel prior to ocular injection achieves adequate local delivery and mitigates the leakage and rapid drug release seen with nanoparticles.

Since topical application of timolol maleate reduces intraocular pressure (IOP) in healthy rodents, this model was used to test the IOP-lowering effects of the slow release timolol palmitate CDAs in rats over 56 days following a single subconjunctival injection versus those of free timolol.

Timolol palmitate CDAs have a critical aggregate concentration of 2.72µM and sustained in vitro release over 28 days. Timolol palmitate CDAs are dispersed throughout in situ gelling hyaluronan-oxime hydrogel and injected into the subconjunctival space of rat eyes. The IOP is significantly reduced for at least 49 days with a single subconjunctival injection of timolol-palmitate CDAs compared to 6 hours for conventional timolol maleate. 

The systemic blood concentrations of timolol are significantly lower, even after 6 hours, for timolol palmitate CDA-loaded hydrogel versus free timolol maleate, thereby potentially reducing the risk of systemic side effects. This innovative approach redefines the role of CDAs and provides a framework for long-acting ocular therapeutics, shifting their perception from a drug screening challenge to a powerful tool for sustained local drug delivery.

REFERENCE:

Dang M, Slaughter KV, Cui H, Jiang C, Zhou L, Matthew DJ, Sivak JM, Shoichet MS. Colloid-Forming Prodrug-Hydrogel Composite Prolongs Lower Intraocular Pressure in Rodent Eyes after Subconjunctival Injection. Adv Mater. 2025 Feb;37(8):e2419306. 

doi: 10.1002/adma.202419306. 

UKEGS Consensus on MIGS

 

Minimally invasive glaucoma surgery (MIGS) offers safer, less invasive alternatives to traditional surgical procedures. Advantages include faster recovery, shorter operations and reduced medication burden via trabecular-bypass or suprachoroidal routes. There is increasing evidence of efficacy justifying adoption and integration into modern glaucoma care, yet considerable inconsistency in practice remains, emphasising the need for guidelines.

Members of UK and Eire Glaucoma Society (UKEGS) have performed a nationwide survey to assess variations in practice and gaps in current policies on MIGS.

The survey found that there was a firm belief among the respondents that MIGS procedures have an important role in glaucoma management and that they can slow vision loss (95%, n = 76), reduce the need for further pressure-lowering incisional glaucoma surgery (94%, n = 75) and lower the burden of medical therapy (98%, n = 78). 

There were some differences in opinion about whether MIGS might divert resources from more critical areas, with 57% (n = 45) expressing this concern, whilst 44% (n = 35) disagreed: highlighting the need for robust cost-effectiveness data to guide resource allocation.

When asked who should be offered MIGS procedures, responses varied: 33% (n = 26) favoured offering MIGS to a minority of carefully selected patients, 55% (n = 44) supported use for all patients taking intraocular pressure-lowering medications, 16% (n = 13) advocated offering MIGS to all glaucoma patients and 5% (n = 4) selected none of these options. 

These findings emphasise the need to establish clear guidelines for standardising patient selection, ensuring that the treating surgeon possesses a comprehensive understanding of glaucoma progression, risk assessment, and alternative treatments options. Such expertise is typically limited to those trained in the subspecialty. 

When asked whether MIGS procedures should be confined to glaucoma specialists, 88% (n = 70) agreed, 85% (n = 67) believed MIGS should not be carried out by surgeons whose primary focus is cataract surgery. This is a valid concern: while carrying out MIGS may be technically feasible, selecting the correct procedure is more complex. The growing range of devices and techniques—often lacking RCT evidence—means balancing immediate risks against long-term benefits demands a detailed understanding of prognosis as well as surgical expertise.

Areas of concern:

The survey raised concerns about independent sector treatment centres (ISTCs) performing MIGS or cataract surgery in glaucoma patients. ISTCs may not be best placed to provide the specialised expertise for the complexities of selecting appropriate MIGS and still less so the careful provision of long-term follow-up patients require.

A major concern is the lack of counselling about MIGS during surgical consultations for glaucoma patients. Not discussing these procedures risks missed opportunities to optimise intraocular pressure control, reduce medication burden, and enhance quality of life. Standardising this discussion could help reduce disparities in access and ensure equitable, comprehensive care.

Future outlook:

Most respondents (61%, n = 48) deemed the process of introducing these new procedures achievable, with 30% (n = 23) describing it as straightforward. However, 10% (n = 8) identified the process as challenging, reflecting mixed institutional readiness. Looking ahead, 78% (n = 62) anticipated an increase in the use of MIGS at their respective hospitals, signalling growing confidence in its clinical benefits and integration into glaucoma management.

Based on these findings, the UKEGS recommends the following guidelines:

1. The decision to perform MIGS should be made by the clinician overseeing a patient’s long-term glaucoma care, with the procedure only being performed by surgeons with specialist training and experience in managing the condition over time
2. Ensure all glaucoma patients undergoing cataract surgery are offered MIGS and made aware of the potential benefits.
3. Develop standardised materials to educate patients on MIGS and the evidence to help decision-making.
4. Limit MIGS use in independent sector treatment centres (ISTCs) to surgeons with glaucoma fellowship training.

REFERENCE:

Abdus Samad Ansari et al. Building consensus on MIGS: insights from a UKEGS survey. Eye volume 39, pages2107–2109.

COMPARISON OF DRI-OCT WITH HRT3

Glaucomatous optic neuropathy involves characteristic optic disc as well as retinal nerve fiber layer (RNFL) structural damage and related functional defects.

Tests of structural integrity include the Heidelberg Retinal Tomograph 3 (HRT3, Heidelberg Engineering GmbH, Heidelberg, Germany) and the continuously evolving technology of optical coherence tomography (OCT).

The HRT3 is a confocal scanning laser tomography (CSLO) device that uses a diode laser (670 nm) to scan the retinal surface at multiple consecutive parallel focal planes and produces repeatable and reproducible three-dimensional (3D) topographical images of the ONH and peripapillary RNFL. After image acquisition, the margins of the optic nerve head (ONH) need to be outlined by a manually drawn contour line to calculate ONH stereometric parameters. HRT3 also provides two different algorithms for ONH anatomy classification: the Moorfields regression analysis (MRA) that requires a contour line to be placed, and the newer contour-line independent Glaucoma Probability Score (GPS). The quantitative and objective measures of these structures are consequently classified as within normal limits (WNL), borderline, or outside normal limits (ONL) by automatic comparison with an ethnic-selectable normative database of eyes.

Deep range imaging OCT (DRI-OCT, Triton, Topcon, Tokyo, Japan) is a recently introduced swept-source OCT (SS-OCT) that uses a center wavelength of 1,050 nm and a bandwidth of approximately 100 nm compared to the fixed 850 nm wavelength of spectral-domain OCT (SD-OCT). The instrument achieves a high scan speed (100,000 A-scans/second) that allows for the acquisition of high-quality wide-field images containing both the ONH and the macula in a 12 mm × 9 mm single scan. SS-OCT, similar to SD-OCT, also provides separate standard macula and optic disc scan modes. Both thickness measurement values and normative comparisons are provided for all SS-OCT measurements.

DRI-OCT Triton: 3D wide(H) glaucoma report. A 75-year-old female with primary open-angle glaucoma in her left eye.
(A) Conventional color photography of the ONH. (B, C) macular GC analysis*. (D) Color-coded RNFL thickness map that corresponds to numeric RNFL thickness measurements. (E) SuperPixel-200 map. The uncolored pixels indicate the normal range, whereas the yellow- and red-colored pixels indicate abnormality at P = 1-5% and P < 1% of the normal level, respectively. (F) cpRNFL analysis*. (G) Numeric measurements of five ONH parameters

Kourkoutas and colleagues from Greece, have performed a study to determine the diagnostic performance of the ONH, macular, and circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements of wide-field maps (12 × 9 mm) using SS-OCT compared to measurements of the ONH and RNFL parameters measured by HRT3. 

They also evaluated the diagnostic ability of wide-field DRI-OCT thickness measurements (optic disc, RNFL, and macular) to differentiate glaucomatous from healthy eyes and compared them with the six main ONH stereometric parameters as well as with the GPS and MRA classification algorithms of the HRT3.

The authors found the highest sensitivities were achieved by the DRI-OCT categorical parameters of Superpixel-200 map and cpRNFL (12 sectors) thickness analysis. The best performing HRT3 continuous parameter was rim volume (AUC = 0.829, 95% confidence interval (CI) = 0.735-0.922), and the best continuous parameter for DRI-OCT wide-field was vertical CDR (AUC = 0.883, 95% CI = 0.805-0.951), followed by total cpRNFL thickness (AUC = 0.862, 95% CI = 0.774-0.951). Area under the curve (AUC) for disc area, rim area, linear CDR, and RNFL thickness were not significantly different between the two technologies. Using either the most or the least specific criteria, SuperPixel-200 map always showed the highest sensitivity among the categorical parameters of both technologies (82.1% and 89.7%, respectively). The highest sensitivity among HRT3 classification parameters was shown by MRA and GPS classification algorithms.

The study concluded that both wide-field DRI-OCT maps and HRT3 have good diagnostic performance in discriminating glaucoma from healthy eyes. However, DRI-OCT thickness values and normative diagnostic classification report the best performance.

REFERENCE:

Kourkoutas D, Triantafyllopoulos G, Georgiou I, Karamaounas A, Karamaounas N, Sotiropulos K, Kapralos D. Comparison of Diagnostic Ability Between Wide-Field Swept-Source Optical Coherence Tomography Imaging Maps and Heidelberg Retina Tomograph 3 Optic Nerve Head Assessment to Discriminate Glaucomatous and Non-glaucomatous Eyes. Cureus. 2022 Aug 19;14(8):e28188. doi: 10.7759/cureus.28188. PMID: 36158420; PMCID: PMC9482818.

24-HOUR FLUCTUATIONS IN IOP FOLLOWING TREATMENT

 

Glaucoma patients are assessed in the clinic during the office hours and their IOP checked in the sitting position. 

However, supine positioning during sleeping hours is associated with decreased blood pressure and increased IOP, which results in decreased perfusion to the eye, including the optic nerve. It has been theorized that this reduced ocular perfusion pressure (OPP) may increase optic nerve damage and associated vision loss.

Fluctuation in IOP over a 24-hour period is attributed to autonomic or humoral control, changes in vascular tone, and bodily postural changes. 

A pilot study to evaluate and compare the 24-hour habitual fluctuations in IOP and OPP in glaucoma patients treated with medical therapy, selective laser trabeculoplasty (SLT) or trabeculectomy was performed by Ruparelia and colleagues from the Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, NS, Canada.

Recruited patients were admitted to the sleep lab for 24-hour serial habitual IOP and blood pressure measurements. IOP and OPP fluctuation among the 3 treatment groups were compared.

The IOP measurements were obtained using Goldmann applanation tonometry and with the patient in upright position. Nocturnal (8 pm, 12 am, 4 am) IOP measurements were obtained via Perkins applanation tonometry and with the patient in the supine position for at least 30 minutes prior to measurement. Brachial blood pressure (BP) was measured using an automated sphygmomanometer. 

Thirty three (33) eyes from 33 patients were recruited in this study, including 11 patients in the medical therapy group, 11 patients in the SLT group, and 11 patients in the trabeculectomy group. 

The medical therapy group was found to have significantly higher 24-hour IOP fluctuation (8.3 ± 1.6 mmHg) than the SLT (3.5 ± 1.9 mmHg) and trabeculectomy (4.3 ± 1.3 mmHg) groups (P < 0.001). 

Mean 24-hour OPP fluctuation was also significantly higher in the medical therapy group (18.5 ± 4.0 mmHg) than the SLT (11.9 ± 7.3 mmHg) and trabeculectomy (14.1 ± 3.9 mmHg) groups (P < 0.05). 

No difference in IOP or OPP fluctuation was found between SLT and trabeculectomy groups (P > 0.05).

Therefore, both SLT and trabeculectomy may be more effective in reducing 24-hour IOP and OPP fluctuation than medical therapy alone. IOP and OPP fluctuation was comparable between SLT and trabeculectomy cohorts. 

REFERENCE:

Ruparelia S, Bonatti R, Murphy JA, Nicolela MT, Eadie BD, Chauhan BC, Dyachok OM, Shuba LM. Twenty four-hour intraocular pressure fluctuation in treated glaucoma patients: a pilot study. Can J Ophthalmol. 2025 Aug;60(4):216-221. doi: 10.1016/j.jcjo.2024.11.010. Epub 2025 Jan 14. PMID: 39719016.

HEAD ELEVATION AND GLAUCOMA

Several nighttime events including increased IOP, decreased ocular perfusion pressure (OPP), and possibly obstructive sleep apnea (OSA) contribute to the development and progression of glaucomatous optic neuropathy. These events may explain the occurrence and progression of glaucomatous disease in the setting of seemingly controlled office-measured IOP. [1]

A study by Buys et al., has shown the 30-degree head-up sleeping position lowers IOP compared with the flat position. Although this effect varies between individual patients, mean IOP was 20% lower in one third of patients in this series.[2]

Several studies have shown that raising the bed head by 30-degrees significantly lowers IOP compared to the supine position. However, the method applied to elevate the head plays a significant role in IOP reduction. For example, while bed head elevation (BHE) is useful, resting on multiple pillows (MP) does not appear to offer the same IOP reduction in glaucoma patients.[3]

Some researchers studied the effect of sleeping in a head-up position using a wedge pillow in glaucoma patients, and healthy subjects. They have demonstrated reduction of mean IOP by 1.5–3.2 mm Hg in the head-up position compared with the flat position.[3]

Lazzaro et al also studied the effect of sleeping in a 20° head-up position in 15 glaucoma patients and 15 non-glaucoma patients. They demonstrated lower nocturnal IOPs (−1.5 mm Hg) with head-up position as compared with the head-flat position in patients with and without glaucoma.[4]

However, Natasha G reported that lying down increases IOP but also improves ocular blood flow. This could affect progression of glaucomatous optic nerve degeneration.[5]

REFERENCES:

1. Aref AA. What happens to glaucoma patients during sleep? Curr Opin Ophthalmol. 2013 Mar;24(2):162-6.
2. Buys YM, Alasbali T, Jin YP, Smith M, Gouws P, Geffen N, Flanagan JG, Shapiro CM, Trope GE. Effect of sleeping in a head-up position on intraocular pressure in patients with glaucoma. Ophthalmology. 2010 Jul;117(7):1348-51.
3. Yeon DY, Yoo C, Lee TE, Park JH, Kim YY. Effects of head elevation on intraocular pressure in healthy subjects: raising bed head vs using multiple pillows. Eye (Lond). 2014 Nov;28(11):1328-33. 
4. Lazzaro EC, Mallick A, Singh M, Reich I, Elmann S, Stefanov DG, et al. The effect of positional changes on intraocular pressure during sleep in patients with and without glaucoma. J Glaucoma. 2014;23:282–287.
5. https://www.medscape.com/viewarticle/night-shift-should-patients-glaucoma-sleep-their-head-raised-2025a10005rn

Seeing the bigger picture in glaucoma care

 

In some cases, systemic causes can be associated with glaucoma. 

Occasionally, it becomes difficult to understand the mechanism of glaucoma in patients. In such cases systemic evaluation might prove to be a useful approach. 

touchOPHTALMOLOGY recently conducted this interview to have a view about this issue.

The complete interview is available at this link:

https://touchophthalmology.com/insight/seeing-the-bigger-picture-in-glaucoma-care/

RETINITIS PIGMENTOSA AND GLAUCOMA

Retinitis pigmentosa (RP) is a rare inherited retinal disorder, characterized by night-blindness and ultimately loss of vision due to involvement of the macula and optic nerve. The worldwide prevalence of RP is about 1 in 4000 for a total of more than 1 million patients affected.

A few studies have been done to analyse the association of RP with glaucoma, especially angle closure glaucoma (ACG). Tao et al have performed a meta-analysis to study the incidence and association between the two conditions. [1]

The meta-analysis involved 8 observational studies (n=31,501 patients; 456 events), 3 of which were of comparative design. Of this pooled population, there were 29,363 patients with RP (238 events). Across all studies, the pooled incidence of ACG with RP was 1.30% [95% CI (0.71–2.36), I2: 97%]. In the comparative analysis, patients with RP had a significantly higher risk of developing ACG [RR: 2.02, 95% CI (1.61–2.55), I2: 0%] compared with patients without RP.

Pradhan et al, studied 618 patients of RP. In their study, the prevalence of primary angle-closure suspects was 2.9%, primary angle closure was 0.65%, and primary angle-closure glaucoma (PACG) was 2.27%. In contrast, the prevalence of primary open-angle glaucoma was 1.29%. The prevalence of PACG in those older than 40 years was 3.8% (95% confidence interval: 1.6–6.0). The study found that the prevalence of PACG in RP patients over 40 years was higher than that found in the general population of a similar age (3.8% vs. 0.8%). [2]

Hung et al, used the Taiwan National Health Insurance Research Database, to compare risk and association between RP and PACG. They enrolled 6223 subjects with RP and 24892 subjects for comparison. The mean age of the cohort was 49.0 ± 18.1 years. The RP group had significantly higher percentages of diabetes mellitus, hypertension, and hyperlipidaemia. The cumulative incidence of PACG in patients with RP was 1.61%, which was significantly higher than that in the comparison group (0.81%, p < 0.0001). According to the univariate Cox regression analysis, the hazard of PACG development was significantly greater in the RP group, with an unadjusted HR of 2.09 (95% confidence interval [CI], 1.64–2.65). The increased risk persisted after adjusting for confounders (adjusted HR = 2.18; 95% CI, 1.76–2.72).

This nationwide population-based cohort study showed that people with RP are at a significantly greater risk of developing PACG than individuals without RP. [3]

These studies and meta-analysis have shown that there is a significantly higher association between RP and PACG across all age groups, but especially for those above 40 years of age. Monitoring and assessment of these higher risk individuals should be standardized in order to provide optimum care.

REFERENCES:

1. Tao BK, Wong M, Shunmugam M, et al. Incidence and Association of Angle Closure Glaucoma in Retinitis Pigmentosa: A Meta-Analysis. Journal of Glaucoma 34:549-554;2025. | DOI: 10.1097/IJG.0000000000002570.
2. Pradhan, Zia S; Shroff, Sujani; Bansod, Apurva; et al. Prevalence of primary angle-closure disease in retinitis pigmentosa. Indian Journal of Ophthalmology 70:2449-2451;2022. | DOI: 10.4103/ijo.IJO_3189_21.
3. Hung MC, Chen YY. Association between retinitis pigmentosa and an increased risk of primary angle closure glaucoma: A population-based cohort study. PLoS One. 2022 Sep 9;17(9):e0274066. doi: 10.1371/journal.pone.0274066. PMID: 36083972; PMCID: PMC9462784.

Altris AI GLAUCOMA MODULE

 

Altris AI is an artificial intelligence platform for OCT analysis, apparently capable of detecting more than 70 retinal pathologies and biomarkers, the highest among such technologies worldwide.

Altris AI has recently launched an advanced glaucoma "Optic Disc Analysis module" for OCT scans.

Traditionally, OCT results are dependent on normative databases pre-loaded in the machine. These databases can be insufficient or skewed for populations not usually seen in the region. For example, the machine can have more caucasian datasets, even though the population being evaluated is Asian or African. 

The new module evaluates optic disc parameters using OCT, providing personalized assessments by accounting for individual disc sizes and angle of rim absence. This tailored approach eliminates reliance on normative databases, making evaluations more accurate and patient-specific.

Key parameters evaluated by Altris AI’s Optic Disc Analysis include:

1. Disc area
2. Cup area
3. Cup volume
4. Minimal Cup depth
5. Maximum Cup depth
6. Cup/Disc area ratio
7. Rim Absence angle
8. Disc-Damage Likelihood Scale (DDLS)

Altris AI’s platform assigns a severity score for optic disc damage on a scale from 1 to 10, offering valuable insights into glaucomatous changes. Furthermore, it enables cross-evaluation across different OCT systems, allowing practitioners to analyze both macula and optic disc pathology, even when data originates from multiple OCT devices.

By combining GCC Asymmetry (a program developed by Altris AI previously, designed to detect early risk of glaucoma), and Advanced Optic Disc analysis for glaucoma, this technology enables eye-care practitioners to make faster evaluations and explore a wider range of treatment options. This streamlined approach empowers users with timely, actionable data, ultimately improving patient outcomes and care.

This innovation not only reduces false positive referrals but also enhances early detection and treatment planning—ensuring better outcomes for patients and optimizing healthcare resources.

REFERENCE:

https://aiineyecare.com/altris-ai-introduces-advanced-optic-disc-analysis-for-glaucoma/#

PreserFlo Microshunt occlusion

Bonatti et al have presented the successful resolution of early fibrin occlusion of PreserFlo MicroShunt with Nd:YAG laser treatment. It is regarded as the first reported case of such a nature.

The PreserFlo microshunt device is indicated in patients with moderate or advanced open-angle glaucoma who require further intraocular pressure (IOP) reduction to prevent disease progression. 

The 70-mm lumen implant redirects aqueous fluid from the anterior chamber to the subtenon space. The microshunt works immediately after its implantation, significantly reducing the IOP, typically in the single digits on the initial post-operative period.

Obstruction of the implant lumen can reduce the aqueous flow through the shunt and prevent this pressure reduction.

The authors performed a PreserFlo MicroShunt implant with phacoemulsification and acrylic intraocular lens implantation on the left eye of a 64-year-old male patient with primary open-angle glaucoma (POAG).

On the first postoperative day, he presented with an uncomfortable left eye with best corrected visual acuity (BCVA) of 6/15, mild corneal edema, and a centered intraocular lens. No filtering bleb was observed and IOP in that eye was 39 mmHg. The intracameral portion of the PreserFlo MicroShunt was in a good position in the anterior chamber, but fibrin strands were observed in the AC going toward the internal ostium of the shunt.

Apparently, the fibrin deposition was limiting drainage through the shunt. The authors used neodymium-doped yttrium aluminum garnet (Nd:YAG) laser to clear the obstructing material. 

The material was lysed under direct visualization using 10 single shots with a power of 1.1 mJ. 

Upon breaking the material, the authors immediately observed a fibrin strand being aspirated into the shunt lumen, indicating patency of the implant. However, 10 minutes after the procedure, the filtering bleb remained flat, and the IOP was 38 mmHg, without any evidence of fibrin in the anterior chamber.

It was suspected that the previously noted fibrin strand was trapped inside the shunt lumen and the patient underwent another laser procedure. 

With the aid of a Ritchie lens, the authors lasered the midsection of the shunt's lumen under the conjunctiva. Two single shots were given with a power of 1.0 mJ until gas bubbles were observed inside the lumen. After 15 minutes, the patient was symptomatically comfortable, an elevated filtering bleb was observed, and the IOP was 12 mmHg. 

At the 1-week postoperative visit, there was no evidence of fibrin in the AC, BCVA was 6/6 and IOP was 4 mmHg. 

At his last visit, 12 months after surgery, his IOP was 15 mmHg with brimonidine-timolol combination twice daily.

REFERENCE:

Bonatti R, Hodgson K, Nicolela M. Successful resolution of early fibrin occlusion of PreserFlo MicroShunt with Nd:YAG laser treatment. Can J Ophthalmol. 2025 Jun;60(3):e482-e485. doi: 10.1016/j.jcjo.2025.01.003. Epub 2025 Feb 6. PMID: 39870357.

PROSTAGLANDINS & RISK OF UVEITIS

Prostaglandin Analogues (PGAs) have often been regarded as pro-inflammatory and contraindicated in situations where there is risk of inflammation, such as neovascular glaucoma (NVG).

Chauhan et al have published a study to evaluate the risk of uveitis among patients starting on topical glaucoma therapy.

The retrospective study utilized the Sight Outcomes Research Collaborative (SOURCE) Ophthalmology Data Repository data from 10 health systems contributing to the SOURCE data repository. 

Adult glaucoma patients who were recently started on topical glaucoma therapy were included in the study. The anti-glaucoma medications included prostaglandin analogs [PGAs], beta-blockers [BBs], alpha agonists [AAs], and carbonic anhydrase inhibitors [CAIs].

Patients with pre-existing documentation of uveitis were excluded.

The main outcome measure was the incidence of uveitis within 3 months of initiating therapy with different topical glaucoma medications.

The study included 67517 patients who were newly prescribed a topical glaucoma medication. 

A total of 567 patients (0.87%) developed uveitis within 3 months of initiating the therapy. 

The incidence of uveitis was 1.95%, 1.68%, 1.63%, and 0.32% for users of BBs, CAIs, AAs, and PGAs, respectively.

After adjusting for sociodemographic factors, individuals using topical BBs, AAs, and CAIs had significantly higher odds of developing uveitis versus those using PGAs (P < 0.001 for all comparisons).

The study concluded that the use of PGAs was not associated with higher odds of developing uveitis compared with other classes of topical glaucoma medications.

REFERENCE:

Chauhan MZ, Elhusseiny AM, Marwah S, Sallam AB, Stein JD, Kishor KS; SOURCE Consortium. Incidence of Uveitis Following Initiation of Prostaglandin Analogs versus Other Glaucoma Medications: A Study from the Sight Outcomes Research Collaborative Repository. Ophthalmol Glaucoma.2025;8:126-132.

REMYELINATION BY THERAPEUTICALLY ENHANCED OLIGODENDROGENESIS

 

Myelin, made by oligodendrocytes enwrapping axons with lipid-rich membranes, is essential for proper central nervous system (CNS) function. Loss of oligodendrocytes and myelin, known as demyelination, induces severe delay and failure of action potential propagation, leaves neurons and their axons vulnerable to degeneration, and causes motor, sensory, and cognitive impairment.

Demyelination is typically followed by a period of heightened new myelin formation known as remyelination, which can restore action potential propagation and prevent neurodegeneration. Remyelination is carried out primarily by newly formed oligodendrocytes.

However, the endogenous remyelination response is often incomplete, resulting in chronic demyelination and limited functional recovery.

Myelin loss, including in visual gray matter, is a common feature of several neurodegenerative diseases and injury conditions, and is present in normal aging. In addition, myelin is malformed or present in insufficient levels in several neurodevelopmental and neuropsychiatric disorders. By promoting the formation of new oligodendrocytes and myelin, remyelination therapies may be clinically important for numerous neurological conditions.

Researchers have shown that endogenous remyelination is driven by recent oligodendrocyte loss and is highly efficacious following mild demyelination, but fails to restore the oligodendrocyte population when high rates of oligodendrocyte loss occur quickly.

Treatment with a high dose of LL-341070 substantially increased regenerative oligodendrogenesis during remyelination. Thus, incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function.

The authors concluded that oligodendrocyte gain rate during remyelination is driven by recent oligodendrocyte loss, rather than a drive to reestablish oligodendrocyte numbers, indicating that acute signaling around the time of the loss of myelinating oligodendrocytes induces new oligodendrocyte formation. However, the exact source of the signal is unknown, and it is unclear if it involves direct signaling from damaged oligodendrocytes or is mediated by other cell types.

REFERENCE:

Della-Flora Nunes, G., Osso, L.A., Haynes, J.A. et al. Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function. Nat Commun 16, 732 (2025). https://doi.org/10.1038/s41467-025-56092-6.

 

ANTIBODY-MEDIATED TREATMENT OF GLAUCOMA

 

Early-onset familial glaucoma is attributed to nonsynonymous mutations in the gene encoding myocilin. The protein myocilin is secreted at relatively high levels in the trabecular meshwork (TM) extracellular matrix. Mutant myocilin aggregates intracellularly in the endoplasmic reticulum (ER). Subsequent ER stress causes cytotoxicity that hastens dysregulation of intraocular pressure, the primary risk factor for most forms of glaucoma.

Recombinant antibodies represent an emerging class of versatile and powerful therapeutics to treat protein conformational and misfolding associated with neurodegenerative diseases. Glaucoma management has entered a new phase with the development of antibodies targeting the aggregation-prone β-propeller olfactomedin (OLF) domain of myocilin, variants of which comprise the strongest genetic link to glaucoma.

These new antibodies target the domain of myocilin that misfolds in the ER and causes pathogenic cytotoxicity. These antibodies degrade aggregating mutant myocilin in situ by rerouting mutant myocilin for lysosomal degradation.

Clearance of OLF-resident myocilin mutants is hindered by aberrant interactions with molecular chaperones such as glucose-regulated protein 94 (Grp94), leading to the accumulation of misfolded proteins, ER stress, and subsequent TM cell death.

Multi-centric research by Ma and colleagues has discovered two recombinant antibodies: anti-OLF1 recognizes a linear epitope, while anti-OLF2 is selective for natively folded OLF and inhibits aggregation in vitro. By binding OLF, these antibodies engage autophagy/lysosomal degradation to promote degradation of two pathogenic mutant myocilins.

The interaction between Grp94 and mutant myocilin can be abrogated with selective small molecules targeting Grp94 or by downregulation of Grp94 with siRNA.

Treatment with Grp94-targeted small molecules or siRNA leads to the clearance of mutant myocilin by autophagy, similar to what is observed with anti-OLF1 and anti-OLF2.

This research shows the promise of antibodies in the treatment of familial open-angle glaucoma associated with myocilin.

REFERENCE:

Ma MT, Qerqez AN, Hill KR, Azouz LR, Youngblood HA, Hill SE, Ku Y, Peters DM, Maynard JA, Lieberman RL. Antibody-mediated clearance of an ER-resident aggregate that causes glaucoma. PNAS Nexus. 2024 Dec 10;4(1):pgae556. doi: 10.1093/pnasnexus/pgae556. PMID: 39726989; PMCID: PMC11670252.

VASCULAR DENSITY AND PERFUSION IN GLAUCOMA

 

Optical coherence tomography angiography (OCTA) is a fast, noninvasive imaging technique that offers quantitative and volumetric evaluations of both the structural and vascular features of the retina and optic nerve. The changes observed in OCTA correlate topographically with the functional alterations identified through visual field assessments and the structural modifications noted on OCT.

There have been a couple of studies to analyze the radial peripapillary capillary vessel density (RPC VD) in glaucoma.

Joseph et al. have studied the peripapillary and macular perfusion densities in 20 eyes of POAG patients, 20 of NTG, and 15 of NTG, and compared them with normal eyes by OCTA analysis.  

All POAG, PACG, and NTG patients showed a lesser peripapillary perfusion density (PD) compared to normal subjects in all quadrants, which was statistically significant (P < 0.002).

Also, all POAG, PACG, and NTG patients showed a lesser superficial perifoveal plexus PD compared to normal subjects in all zones, which was statistically significant (P < 0.004).

In NTG, the peripapillary PD of the superior quadrant showed the least PD (P < 0.001), and in PACG, the inferior, nasal, and temporal quadrants showed the least PD, which was statistically significant (P < 0.002).

The mean peripapillary flux index of the outer zone was lowest in the PACG group, which was statistically significant (P < 0.001).

All forms of glaucoma (POAG, PACG, and NTG) were associated with decreased blood supply to the ONH and the perifoveal zone.

Apart from the mechanical damage to the optic nerve head, PACG is associated with significant retinal microvascular impairment.

Significant microvascular impairment in the perifoveal area in NTG is characterized by decreased PD in the outer and full zones.

Ashour et al have shown that RPC VD is reduced in eyes with glaucomatous cupping, and not in those with physiological cupping or in normal eyes. The study included 98 eyes from 98 patients, divided into 3 groups. Group 1 included 30 eyes with primary open-angle glaucoma, group 2 included 28 normal eyes with physiological cupping (normal OCT and no evidence of glaucoma), and group 3 included 40 age-matched normal eyes (vertical cup/disc ratio ≤0.5).

The study found significantly lower RPC VD across all retinal quadrants, compared to the other groups (P<0.001) in Group 1. But no significant differences were found between Groups 2 and 3 (P=0.559). Therefore, OCTA can be used to differentiate between glaucomatous and physiological cupping.

REFERENCES:

Joseph, Rachel; Apoorva, N.; Nayak, Lakshmi D.. Comparison of vascular parameters in primary open-angle glaucoma, primary angle closure glaucoma, and normal tension glaucoma with healthy subjects using optical coherence tomography angiography. The Pan-American Journal of Ophthalmology 7(1):143, April 2025. | DOI: 10.4103/pajo.pajo_23_25

Ashour DM, Madkour NS, Ebeid WM, Mahmoud RA. Peripapillary Vascular Density Differentiates Glaucomatous Cupping From Physiological Cupping Using Optical Coherence Tomography Angiography. J Glaucoma. 2025 May 1;34(5):415-420. doi: 10.1097/IJG.0000000000002530. Epub 2024 Dec 16. PMID: 39670861.

OPTIC DISC-RNFL IN PEDIATRIC POPULATION

Optic disc and retinal nerve fiber layer (RNFL) measurements by optical coherence tomography (OCT) are important investigations in detecting glaucoma. However, the results of the OCT measurements are influenced by a normative database with which the measurements are compared. 

The results of the OCT findings in adults are reliable because of the large and stable database. However, in children below 18 years of age, the database is usually not robust, and so the OCT results are not clear.

There have been a few studies of OCT in children, and the results of those studies are being presented here.

Adem et al. reported the average peri-papillary RNFL thickness in children between 6 to 16 years of age was 106.45 9.41 μm; the average macular thickness was 326.44 14.17 μm; and the average macular volume was 0.257 0.011 mm³. The aforementioned OCT measurements were not significantly correlated with age, SE, or AL values (P > .05 for all). [Turk A, Ceylan OM, Arici C, Keskin S, Erdurman C, Durukan AH, Mutlu FM, Altinsoy HI. Evaluation of the nerve fiber layer and macula in the eyes of healthy children using spectral-domain optical coherence tomography. Am J Ophthalmol. 2012 Mar;153(3):552-559.e1.]

Patel et al. have reported the average retinal nerve fiber layer (RNFL) thickness measured with spectral-domain (SD) OCT in children between 5 and 18 years of age to be 102 to 113μm. [Patel A, Purohit R, Lee H, Sheth V, Maconachie G, Papageorgiou E, McLean RJ, Gottlob I, Proudlock FA. Optic Nerve Head Development in Healthy Infants and Children Using Handheld Spectral-Domain Optical Coherence Tomography. Ophthalmology. 2016 Oct;123(10):2147-57.] Susan et al. found the mean peripapillary RNFL thickness in children aged 5 to 15 years to be 107.6 ± 1.2 μm. [Yanni SE, Wang J, Cheng CS, Locke KI, Wen Y, Birch DG, Birch EE. Normative reference ranges for the retinal nerve fiber layer, macula, and retinal layer thicknesses in children. Am J Ophthalmol. 2013 Feb;155(2):354-360.e1.] In a study by Raffa regarding the normative OCT reference ranges in healthy Saudi children, the mean values for RNFL thickness, disc area, rim area, and cup volume were 93.9 μm, 2 mm², 1.6 mm², and 0.3 mm³, respectively. The vertical ratio of cup to disc was 0.4. [Raffa L, AlSwealh SS. Normative optical coherence tomography reference ranges of the optic nerve head, nerve fiber layer, and macula in healthy Saudi children. Saudi Med J. 2023 Nov 28;44(12):1269-1276.] An OCT study of 113 healthy children aged 6 to 17 years with no ocular abnormality except refractive error showed the mean RNFL thickness was 95.6+/-8.7 μm. [Al-Haddad C, Barikian A, Jaroudi M, Massoud V, Tamim H, Noureddin B. Spectral domain optical coherence tomography in children: normative data and biometric correlations. BMC Ophthalmol. 2014 Apr 22;14:53.] A multi-center Spanish study in normal children reported the following data: The mean global RNFL thickness was 97.40 ± 9.0 μm (range, 77-121.7 μm). [Barrio-Barrio J, Noval S, Galdós M, Ruiz-Canela M, Bonet E, Capote M, Lopez M. Multicenter Spanish study of spectral-domain optical coherence tomography in normal children. Acta Ophthalmol. 2013 Feb;91(1):e56-63.]

This study is by Hassan et al. from Iran, 9051 eyes of 4784 children were analyzed.

Vertical cup-to-disc ratio	0.45±0.15(0.45–0.46) mm
Average cup-to-disc ratio	0.43±0.14 (0.42–0.43) mm
Rim area	1.46±0.25 (1.45–1.47) mm2
Disc area	1.92±0.35 (1.91–1.93) mm2
Cup volume	0.14±0.14 (0.14–0.15) mm3

The mean±SD and 95% confidence intervals (in parentheses)

Hashemi, Hassan; Khabazkhoob, Mehdi; Heydarian, Samira; Emamian, Mohammad Hassan; Fotouhi, Akbar. Optic Disc Measurements in Children by Optical Coherence Tomography. Journal of Glaucoma 32(5):p 361-368, May 2023.

ALCOHOL AND OPEN-ANGLE GLAUCOMA

 

A study by Leo et al, based on the National Institutes of Health All of Us (AoU) Research Program, has reported a significant association between the frequency of consumption of alcoholic drinks and primary open-angle glaucoma (POAG).

The retrospective study utilized the diverse All of Us Research Program. A randomized 1:4 case/control ratio was utilized for POAG patients and randomly selected control patients. χ², bivariable, and multivariable regression were utilized to examine the associations between alcohol use and POAG.

Of the 3876 POAG patients, 2015 (52%) were female, 1943 (50%) were White, 1152 (30%) were Black, 117 (3%) were Asian, and 584 (15%) were Hispanic.

Alcohol use of 4 or more drinks per week was significantly higher in the glaucoma cohort relative to controls (15% vs. 12%, P<0.001). On bivariate analysis, diagnosed alcohol misuse was associated with higher odds of POAG [odds ratio (OR): 1.20, 95% CI: 1.17–1.23, P<0.001].

In multivariable regression, more frequent alcohol use was associated with higher odds of glaucoma; alcohol use with a frequency of 4 or more drinks per week was significantly associated with increased odds of glaucoma (OR: 1.22, 95% CI: 1.03–1.44, P=0.023).

This dose-response relationship was also observed and more pronounced for female participants, where alcohol use frequency of monthly or less was already associated with increased odds of glaucoma (OR: 1.21, 95% CI: 1.002–1.46, P=0.048).

RESULT:

According to this study, there was a dose-response relationship between alcohol consumption and POAG risk, which was more pronounced in female participants. Overall, a higher frequency of alcohol consumption was associated with an increased risk of POAG; 4 or more drinks per week was significantly associated with a higher risk of glaucoma.

REFERENCE:

Meller LLT, Saseendrakumar BR, Mahmoudinezhad G, Tavakoli K, Wu JH, Parikh A, Bhanvadia S, Moghimi S, Zangwill L, Weinreb RN, Baxter SL. Association Between Alcohol Use and Primary Open Angle Glaucoma. J Glaucoma. 2025 Feb 1;34(2):69-76. doi: 10.1097/IJG.0000000000002529. Epub 2024 Dec 16. PMID: 39670849.

 

LEOS (LASER ENDOSCOPY OPHTHALMIC SYSTEM)

 

BVI Medical, a leading global ophthalmic device company, has received 510(k) clearance from the U.S. Food and Drug Administration (FDA) for its innovative glaucoma surgical system, Leos™ (Laser Endoscopy Ophthalmic System).

Leos™ introduces a novel, more intuitive laser endoscopic cyclophotocoagulation (ECP) procedure that integrates seamlessly into the surgical workflow.

This laser system lowers intraocular pressure by addressing aqueous humor production in a minimally invasive ab interno procedure.

It incorporates unique endoscopic capabilities to provide superior visualization of the eye anatomy in a way not seen in the past, or with the latest imaging systems.

https://www.bvimedical.com/bvi-medical-announces-approval-of-breakthrough-technology-fda-510k-clearance-of-its-laser-endoscopy-ophthalmic-system-leos/

DIRECT SELECTIVE LASER TRABECULOPLASTY (DSLT)

Selective Laser Trabeculoplasty (SLT) is an effective first-line treatment option for patients with open-angle glaucoma and normal-tension glaucoma.

Alcon has improved the delivery system of SLT machines with the development of the Voyager Direct Selective Laser Trabeculoplasty (DSLT) system.

Voyager™ DSLT is designed to automatically deliver 120 laser pulses directly through the limbus to the trabecular meshwork, thereby improving aqueous outflow and reducing intraocular pressure.

The GLAUrious Study comparing DSLT and SLT did not find inferiority of the DSLT procedure at 6 and 12 months of follow-up.

The study demonstrated that DSLT with the Eagle device is effective in providing a clinically meaningful reduction in IOP at 6 months that is sustained out to 12 months.

The protocol included DSLT: 120 shots, 3 ns, 400 µm spot size, energy 1.4–1.8 mJ delivered at the limbus over 2 s. SLT: approximately 100 shots, 3 ns, 400 µm spot size administered 360 degrees at the limbus using any gonioscopy lens, energy 0.3–2.6 mJ.

According to the authors, a sample size of 164 is sufficient to detect a non- inferiority margin of 1.95 mm Hg for change from baseline IOP.

REFERENCE:

Congdon N, Azuara-Blanco A, Solberg Y, Traverso CE, Iester M, Cutolo CA, Bagnis A, Aung T, Fudemberg SJ, Lindstrom R, Samuelson T, Singh K, Blumenthal EZ, Gazzard G; GLAUrious study group. Direct selective laser trabeculoplasty in open angle glaucoma study design: a multicentre, randomised, controlled, investigator-masked trial (GLAUrious). Br J Ophthalmol. 2023 Jan;107(1):62-65. doi: 10.1136/bjophthalmol-2021-319379. Epub 2021 Aug 25. PMID: 34433548; PMCID: PMC9763163.