EYEDROP AIDS

 

Glaucoma is usually seen in elderly individuals. Due to age, other comorbidities, and lack of social support, glaucoma patients have difficulties in instilling the eyedrops prescribed for their disease. Lack of compliance is a significant factor in poor control of intraocular pressure (IOP).

In order to overcome the difficulty in drop instillation, eye drops aids have been devised. Eye drop aids are small, reusable tools that attach to standard medication bottles to ensure accurate alignment, prevent blinking, and make squeezing easier. They reduce drop waste and minimize the risk of touching the eye's surface with the bottle tip.

A few types of eyedrop aids are presented here:

AUTODROP:

Autodrop is a mechanical device designed to facilitate precise eye drop delivery. It attaches to standard eye drop bottles and rests on the cheek bone, ensuring proper alignment and minimizing spillage outside the eye.

Advantages:

• User friendly
• Offers improved accuracy in eye drop delivery
• Ease of use
• Decreased risk of bottle tip contamination
• Decreased risk of injury to the eye surface from the bottle tip

Disadvantages:

• The inconvenience of an additional step.
• May increase the number of drops used for some patients.

AUTOSQUEEZE:

Autosqueeze & Opticare Arthro: These are lever-based attachments designed to increase gripping leverage, making it much easier to squeeze bottles if you have arthritis or grip issues. Autosqueeze is a mechanical device designed to eliminate the difficulty of squeezing the eyedrop bottle. It has a central holder that attaches to standard eye drop bottles and a wing on either side. Squeezing the wings will cause the grooves on the inside of the wing to apply pressure to the eye drop bottle so that one eye drop is released.

Advantages:

• Ergonomic grip
• Helps overcome mobility difficulties
• Can be used in combination with the Autodrop

Disadvantages:

• Inconvenience of an additional step.

NANODROPPER:

Nanodropper is a portable attachment that reduces the size of eye drop droplets, allowing for more efficient dosing and reduced wastage. It attaches to standard eye drop bottles and dispenses smaller, more precise drops, maximizing the number of doses per bottle.

Advantages:

• Precision dosing
• Improved adherence to the medication schedule
• Cost efficiency
• Decreased side effects
• Decreased waste
• Improved accuracy

Disadvantages:

• Learning curve to using the device
• Inconvenience of an additional step
• Extending the bottle life span may increase the risk for contamination
• Its compatibility with different bottle designs may vary.

GENTLEDROP:

GentleDrop is a nose point pivot device, where the eye drop bottle is inserted into a sleeve. That sleeve is then rested on the bridge of the nose, ensuring proper alignment.

Advantages:

• Improved aim
• Minimizing waste
• Reduced risk of bottle tip contamination

Disadvantages:

• Incompatible with some eye drop bottles
• Inconvenience of an additional step
• May be difficult to use for patients with limited dexterity.

EYE DROP GUIDE:

The Eyedrop Guide ensures precise application of eye drops, making it easier for both seniors and children to use. This eyedrop guide aid is compact making it convenient to carry in a bag or pocket for on the go use.

This eyedrop bottle dispenser avoids waste caused by incorrect and extra instillation of drops. This eye dropper aid tool is made of abs material, making it easy to clean and reusable.

All these devices ensure proper application of eyedrops and decrease the efforts required for eyedrop delivery, ensuring maximal compliance.

THERMORESPONSIVE GELS

 

Thermoresponsive gels are typically composed of polymers that exhibit a lower critical solution temperature (LCST). Below this temperature, the polymer exists as a liquid (sol), allowing for easy administration. Upon exposure to physiological temperatures (approximately 37°C), the polymer undergoes a phase transition to form a gel, which can act as a reservoir for sustained drug release.

Mechanism of Action: Sol-Gel Transition:

The sol-gel transition in thermoresponsive gels is driven by changes in the polymer's hydrophilic-hydrophobic balance as the temperature increases. Below the LCST, the polymer chains are hydrated and remain in solution. As the temperature rises above the LCST, the polymer undergoes dehydration, leading to chain collapse and gel formation. This gelation process is reversible, meaning that the gel can return to a sol state if the temperature drops below the LCST. However, in the context of ocular drug delivery, the temperature remains relatively constant, ensuring that the gel remains in place for an extended period.

Advantages in Overcoming Ocular Barriers:

The eye's anatomy presents several barriers to effective drug delivery, including the corneal epithelium, tear film, and conjunctival clearance mechanisms. Thermoresponsive in situ gels offer several advantages in overcoming these barriers:

1. Enhanced Corneal Penetration: The prolonged contact time provided by the gel allows for greater drug absorption across the cornea, increasing the bioavailability of the drug.
2. Reduction of Precorneal Drug Elimination: The gel's viscosity helps to retain the drug on the ocular surface, reducing the rate of drug elimination by tear turnover and blinking.
3. Improved Retention in the Conjunctival Sac: The gel formation in the conjunctival sac prevents rapid drainage of the drug, ensuring that it remains in contact with the ocular surface for a longer period.

These advantages make thermoresponsive in situ gels an attractive option for delivering drugs to the eye, particularly for conditions like glaucoma, where sustained drug delivery is critical for maintaining IOP control.

Applications of Thermoresponsive In Situ Gels in Glaucoma Treatment:

The utilization of thermoresponsive in situ gels for glaucoma treatment offers promising opportunities to address the challenges of sustained drug delivery, improved patient compliance, and enhanced therapeutic efficacy.

Anti-Glaucoma Drugs Formulated in Thermoresponsive Gels:

Several anti-glaucoma drugs have been incorporated into thermoresponsive in situ gel formulations to improve their efficacy and patient adherence. These drugs are primarily aimed at lowering IOP, which is a key modifiable risk factor in glaucoma management. The most commonly used drugs in such formulations include: Prostaglandin analogs, beta blockers, alpha agonists, carbonic anhydrase inhibitors and combination therapies.

Clinical Benefits of Thermoresponsive Gels in Glaucoma:

Thermoresponsive in situ gels offer several clinical benefits in the treatment of glaucoma, especially in terms of improving therapeutic outcomes, patient compliance, and minimizing adverse effects:

1. Sustained IOP Control: One of the primary advantages of thermoresponsive gels is their ability to maintain therapeutic drug levels over extended periods. This sustained release results in more consistent IOP control, reducing fluctuations that can occur with traditional eye drop therapies.
2. Reduced Dosing Frequency: By prolonging the retention time of drugs on the ocular surface, thermoresponsive gels decrease the frequency of administration. Patients who previously required daily or multiple daily doses of medication can potentially achieve adequate IOP control with weekly or biweekly applications. This reduction in dosing frequency is particularly beneficial for elderly patients or those with cognitive or physical limitations.
3. Improved Bioavailability: The gel's ability to remain on the ocular surface for an extended period enhances the penetration of the drug through the cornea, improving its bioavailability and efficacy. This is especially important for drugs that have poor corneal penetration in conventional formulations.
4. Minimized Systemic Absorption: The increased retention of the drug in the eye reduces the risk of systemic absorption and associated side effects, such as cardiovascular or respiratory effects seen with beta-blockers or other medications.
5. Enhanced Patient Compliance: The ease of administration and reduced dosing frequency contribute to better patient compliance, which is critical in managing a chronic disease like glaucoma. Studies have shown that patients are more likely to adhere to simpler treatment regimens, which can ultimately improve clinical outcomes.

REFERENCE:

Maroof M, Pandey AA. Thermo-responsive in-situ gel for ocular glaucoma: A comprehensive review. International Journal of All Research Education and Scientific Methods (IJARESM), ISSN: 2455-6211, Volume 12, Issue 8, August-2024.

DANDELION AND GLAUCOMA

 

Erigeron breviscapus (EB), also known as Dandelion Flower, is the dried whole herb of the Asteraceae plant.

Studies have shown that EB has the effects of dilating blood vessels, improving microcirculation, increasing blood flow, expanding the visual field, and protecting retinal ganglion cell damage in rats caused by elevated intraocular pressure.

A study was conducted using "Network Pharmacology" to elucidate the mechanism of action of EB in the treatment of glaucoma.

Network pharmacology is a branch of science that, based on the theoretical foundations of systems biology and multidirectional pharmacology, utilizes biomolecular network analysis methods to examine the effective components and their synergistic effects in Traditional Chinese Medicine (TCM)  prescriptions or single compounds from both molecular and systemic perspectives.

It scientifically elucidates the pharmacological mechanisms of TCM. Built on the interaction network of “disease-gene-target-drug,” it emphasizes analyzing the molecular correlation patterns between drugs and their therapeutic targets from a systemic and holistic approach.

EB screening in the study identified 12 active ingredients and 161 gene targets for glaucoma treatment.

EB was found to have pharmacological effects such as vasodilation, improvement of microcirculation, and enhancement of blood supply to the heart and brain; regulation of blood lipids, reduction of blood viscosity, and improvement of blood rheology; inhibition of platelet and red blood cell aggregation, promotion of fibrinolytic activity; scavenging of oxygen free radicals, combating lipid peroxidation, and ischemia-reperfusion injury.

The main chemical components of EB have been gradually revealed and elucidated. 

This study identified 50 active components through Traditional Chinese Medicine Systems Pharmacology screening, including quinic acid, ethyl caffeate, and methyl caffeate, all of which are caffeoyl ester compounds. Among the 12 effective active components, most are flavonoids, such as luteolin, quercetin, kaempferol, naringenin, 6-hydroxykaempferol, and baicalein.

Based on network pharmacology, the researchers identified the action targets of 12 active components and the disease targets of glaucoma, and then found the intersection, resulting in a total of 161 targets for EB in the treatment of glaucoma. 

By constructing the drug-active ingredient-target-disease network diagram, it can be seen that EB exhibits a multi-component, multi-target action mode in the treatment of glaucoma.

EB may protect or restore optic nerve function in the treatment of glaucoma by promoting cell proliferation, inhibiting apoptosis.

Therefore, EB treatment of glaucoma is a complex process involving multiple components, multiple target actions, and multi-pathway coordination.

REFERENCE:

Yang E, Zhu Y, Chen X, Xie X, Ma Z. Exploring the potential mechanisms of Erigeron breviscapus in the treatment of glaucoma based on network pharmacology and molecular docking. Medicine (Baltimore). 2025 Aug 15;104(33):e43970. doi: 10.1097/MD.0000000000043970. PMID: 40826712; PMCID: PMC12366968.

BRINZOLAMIDE

 

Brinzolamide is a carbonic anhydrase inhibitor (CAI) used to lower intraocular pressure (IOP) in patients with open-angle glaucoma (POAG) or ocular hypertension (OH).

Brinzolamide is commonly available as a 1% suspension. It can be used in patients unresponsive to beta-blockers or in whom beta-blockers are contraindicated.

Pharmacodynamics:

Pharmacologically, brinzolamide is a highly specific, non-competitive, reversible, and effective inhibitor of carbonic anhydrase II (CA-II). It is able to suppress the formation of aqueous humor in the eye presumably by reducing the rate of formation of bicarbonate ions with subsequent reduction in sodium and fluid transport; and thus, decrease IOP.

Brinzolamide can be added to beta-blockers and prostaglandins. In the latter combination, prostaglandin derivatives improve the uveoscleral outflow but also increase the activity of CA in ciliary epithelium which may lead to a secondary increase in aqueous humor secretion. This may slightly reduce the efficacy of prostaglandin analogues. Topical CAIs inhibit CA-II, thus overcoming the increased ciliary body activity of prostaglandin analogues, and indirectly improving prostaglandin efficacy. 

Brinzolamide could have a secondary possible effect on ocular flow too. Some clinical studies have shown a mild improvement of ocular blood flow.

Pharmacokinetics:

The recommended frequency for topical application is two to three times per day. As monotherapy in patients with POAG or OH, brinzolamide 1% demonstrated IOP-lowering efficacy that was significantly greater than placebo, equivalent to three-times-daily dorzolamide 2% but significantly lower than twice-daily timolol 0.5%. 

Phase III trials have reported that brinzolamide 1% twice- and thrice-daily produced statistically significant IOP reductions from baseline, and that both treatments were clinically equivalent to one another.

Both regimens produce diurnal mean IOP reductions from baseline in the range of 13.2-21.8%.

Side effects:

In clinical trials, brinzolamide 1% was well tolerated causing only non-serious adverse effects that were generally local, transient and mild to moderate in severity. The incidence of the most common adverse events associated with the use of brinzolamide 1% was either similar to (blurred vision and abnormal taste) or significantly lower than (ocular discomfort) with dorzolamide 2%.

Common, but mild side effects: blurred vision; bitter, sour, or unusual taste; itching, pain, watering, or dryness of the eyes; feeling that something is in the eye; headache; runny nose

Rare, but serious: fast or irregular heartbeat; fainting; skin rash, hives, or itching; severe eye irritation, redness, or swelling; swelling in the face, lips, or throat; wheezing or trouble breathing

Precautions:

• Hypersensitivity to other sulfonamides
• Acute angle-closure glaucoma
• Concomitant administration of oral carbonic anhydrase inhibitors
• Moderate-to-severe chronic kidney disease or liver disease.

Corneal decompensation:

In the corneal endothelium, CA-II plays a role in the pumping mechanism, which helps to maintain the relatively dehydrated state of the corneal stroma. Inhibition of this mechanism can cause corneal decompensation and edema, which leads to impaired vision. 

In a randomized, double-blind clinical trial, 372 glaucomatous and OH patients received brinzolamide 1% or timolol 0.5%. After 18 months of treatment, no significant change was found in corneal thickness and corneal endothelium cell density. However, in this study only subjects with healthy corneas were included. Some concern remained in patients with compromised corneas, because in 2 published case reports corneal decompensation has been described in patients with keratopathy after treatment with dorzolamide. 

ALSO SEE= "FIXED DRUG COMBINATIONS": 

https://ourgsc.blogspot.com/2019/10/fixed-drug-combinations-in-glaucoma.html

PREVALENCE OF GLAUCOMA IN EUROPE AND PROJECTIONS TO 2050

 

Stuart et al have performed a “Two-stage, individual participant data meta-analysis” to provide updated glaucoma prevalence estimates and to quantify the current and future burden of disease in Europe.

The analysis is based on population-based European Eye Epidemiology Consortium studies with glaucoma prevalence data based on direct participant examination.

The analysis included 55415 adults ≥40 years of age (mean age, 65.6 years; 53.9% women) from 14 population-based studies (1991-2020).

The European Eye Epidemiology Consortium is a collaborative initiative of >50 European eye studies, including >180 000 participants, with the aim of promoting and facilitating epidemiologic research into common eye diseases.

The results of this analysis are as follows:

• Among the 55415 individuals included in the study, 2021 participants (3.65%) were found to have glaucoma with an age-standardized European prevalence of 2.99%.
• Older age and male sex were associated with higher prevalence.
• Despite regional and diagnostic differences in prevalence estimates, no temporal trend was identified. However, studies based on specialist opinion yielded the highest glaucoma prevalence estimate and those based on modified ISGEO criteria yielded the lowest.
• This is perhaps unsurprising given that ISGEO criteria rely on statistical cutoffs of vertical cup-to-disc ratio and cup-to-disc ratio asymmetry to define structural damage, potentially excluding cases of early disease or other characteristic features of glaucomatous optic neuropathy that may have been considered diagnostic in other studies.
• Primary open-angle glaucoma (POAG) accounted for 79.9% of all cases of glaucoma. Among other subtypes, primary angle-closure glaucoma (PACG) (9.1% of all cases) and secondary glaucoma (11.0% of all cases) were also found. 
• The prevalence for all types of glaucoma showed an increasing trend with age. However, a decline in PACG prevalence was observed after 80 years of age (PACG was most common between 60-74 years of age).
• More than half (56.4%) of cases were undiagnosed previously (new cases), with a higher proportion of undetected disease in younger participants, including >80% in those <55 years of age.
• Based on the analysis, in 2024 the burden of cases was estimated to be of 12.3 million individuals with glaucoma in Europe, including 6.9 million individuals with undiagnosed disease.
• Significant differences were found across geographic regions, with the lowest prevalence observed in Western Europe and the highest in Eastern Europe.
• Despite projections of an overall decline in total population (~11.8%) over the next 26 years, the number of glaucoma cases is projected to increase to 13.52 million (þ10.3%) by 2050. Thus, the burden of glaucoma patients is projected to grow by >1 million people by 2050 because of changing population age structure, with a preponderance of primary open-angle glaucoma.
• The annual rate of change is expected to slow, however, with a peak of 13.63 million cases reached by 2045, before a decline in total case numbers is seen.

The study concluded that:

The burden of glaucoma may be significantly underestimated if estimates are based solely on published summary statistics, rather than individual-level data, and this may have broader implications for other age-related conditions.

REFERENCE:

Stuart KV, de Vries VA, Schuster AK, Yu Y, van der Heide FCT, Delcourt C, Cougnard-Grégoire A, Schweitzer C, Brandl C, Zimmermann ME, Heid IM, Farinha C, Coimbra R, Luben RN, Hayat S, Khaw KT, Stingl JV, Pfeiffer N, Berendschot TTJM; Maastricht Study Consortium; Arnould L, Creuzot-Garcher C, Hogg R, Wright DM, Azuara-Blanco A, Vergroesen JE, Klaver CCW, Ramdas WD, Topouzis F, Giannoulis DA, Bikbov MM, Kazakbaeva GM, Jonas JB, Jansonius NM, Bourne RRA, Quigley HA, Foster PJ, Khawaja AP; European Eye Epidemiology Consortium. Prevalence of Glaucoma in Europe and Projections to 2050: Findings from the European Eye Epidemiology Consortium. Ophthalmology. 2025 Oct;132(10):1114-1124. doi: 10.1016/j.ophtha.2025.06.002. Epub 2025 Jun 9. PMID: 40499787.

MICRO INTERVENTIONAL DYNAMIC OUTFLOW CURVE (imDOC)

Micro-interventional dynamic outflow curve (miDOC) is a revolutionary technology developed by Professor Sean Ianchulev, from the New York Eye and Ear Infirmary (NYEE), USA.

While performing glaucoma procedures without miDOC, surgeons have no way of checking a patient’s exact ocular flow and pressure, a critical variable in the operating room. They can only check intraocular pressure before and after the procedure, which occasionally leaves unpredictable outcomes.

This has affected the precision of glaucoma surgery. Some surveys have reported more than 50 percent of the patients undergoing trabeculectomy and drainage device implants unable to achieve complete postoperative success and medication independence. In some cases, it is not until the follow-up appointment that ophthalmologists discover the procedure may not have worked and/or has possible complications.

miDOC allows eye surgeons to measure and respond to critical fluid dynamics inside the eye in real time – an advance that may significantly improve precision and outcomes in glaucoma and other ophthalmic procedures.

During surgery, miDOC enables continuous measurement of key parameters including:

1. Pressure
2. Flow
3. Outflow facility
4. Ocular rigidity/Compliance

These measurements provide new insight into how surgical interventions affect the eye in real time.

By providing real-time biometric feedback, miDOC has the potential to elevate glaucoma surgery to a new era of digital-guided precision.

NYEE is the only eye center in the US to use this technology and conduct the first-in-human clinical study. Surgeons started using it in patients in July 2025 and have completed the first 20 cases. According to investigators, all procedures were successfully completed with intra-operative biometric guidance.

Investigators at NYEE plan to further refine the technology and pursue regulatory pathways for broader clinical use. 

Slow-Coagulation Continuous-Wave Cyclophotocoagulation

 

Slow coagulation continuous wave trans-scleral cyclophotocoagulation (CW-TSCPC) is an emerging relatively noninvasive intervention that can be used in different patient populations. The procedure uses the traditional G-probe and continuous wave (CW) laser, with a modified balance of power and duration for enhanced safety compared to the conventional protocol.

Slow coagulation CW-TSCPC delivers photocoagulative laser energy to the ciliary body using a fixed lower power of energy over a longer duration, thereby theoretically decreasing the risk of collateral damage surrounding the ciliary body and severe inflammation from necrotic high energy disruption of the ciliary body.

The greater pressure-lowering effect observed with Slow coagulation CW-TSCPC may be attributed to more substantial structural changes in the ciliary body, whereas the micropulse (MP) technique does not appear to produce significant histologic changes.

The standardized technique involves the following parameters: 1250 mW, 4 s/spot, 20 spots, delivering a total energy of 100 J.

The recently described variation—the Double-Arc Slow-Coagulation protocol—employs a dual-row application strategy, divided in upper (ciliary body shadow) and lower (1.5 mm behind) arcs. Initial results with this technique have demonstrated favorable IOP control and a low rate of complications in the management of refractory glaucomas.

The most frequent complications reported in a study comparing Slow coagulation CW-TSCPC with MP-LT are clinically significant visual acuity loss (20.0% in the Slow coagulation CW-TSCPC group and 26.7% in the MP-LT group), transient anterior segment inflammation (30.0% vs. 23.3%), and transient corneal edema (13.3% vs. 20.0%). 

Pupillary abnormalities, cystoid macular edema, iris synechiae, and iris neovascularization occur with varying frequencies. Hypotony has been reported in 6% patients following Slow coagulation CW-TSCPC.

Pupillary abnormalities are often linked to a more anterior application of the laser, closer to the iris root.

A two-center, randomized, clinical trial in a population of patients with refractory glaucoma, Slow coagulation CW-TSCPC demonstrated superior IOP control, with fewer IOP-lowering medications and a lower rate of surgical failure compared to MP-LT over an 18-month follow-up. Fewer reapplications and additional surgeries were required in the Slow coagulation CW-TSCPC group.

Another study of pseudophakic glaucoma reported lowering of IOP from 27.5±9.8 mm Hg preoperatively to 16.1±6.3 mm Hg postoperatively with a mean percentage reduction of IOP of 42.1% and 75.7% of eyes having ≥20% decrease in their baseline IOP.

Another study in virgin eyes reported that 52.2% of the treated eyes had ≥20% reduction of IOP from baseline. Interestingly, the IOP reduction was noted to more in patients with higher baseline IOP (>21 mm Hg). Slow coagulation TSCPC treatment resulted in a significant decrease of glaucoma medications from 3.8±1.0 to 2.8±1.4 at baseline and last visit, respectively. 

These findings highlight Slow coagulation CW-TSCPC as a reliable technique for managing different types of patients with glaucoma. 

RHEUMATOID DISEASES AND GLAUCOMA RISK

Glaucoma is characterized by retinal ganglion cell (RGC) neurodegeneration. Elevated intraocular pressure (IOP) is a major risk factor for the development of glaucomatous optic neuropathy and RGC loss. However, pressure-independent mechanisms also play a role in RGC damage. 

Both antibodies and CD4 T–cells as well as microbiota take part in the pathogenesis of both glaucoma and rheumatoid arthritis (RA).

Heat shock proteins (HSPs) which originate in bacteria cross-react with RGC epitopes and were detected in a rat model of retinal injury. Enhanced expression of HSPs in the retina was associated with glaucoma-like neuropathology and previous studies have also suggested a pathogenic role for HSPs in RA. 

Since autoimmunity and inflammation, the main characteristics of rheumatic diseases, are related to glaucoma, it was suggested that glaucoma should be included in the spectrum of autoimmune disorders.

A few studies related to the association of rheumatoid diseases and glaucoma are presented here:

1. A Mendelian randomization (MR) analysis was performed by Meng et al, to investigate the causal effects of six common rheumatic diseases on glaucoma. MR is an established approach for making causal inferences in epidemiology.

Six rheumatic diseases were included: ankylosing spondylitis (AS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sicca syndrome/Sjögren’s sydrome (SS), dermatomyositis (DM), and gout.

Using two-sample MR, the authors found that AS is associated with a higher risk of both POAG and PACG.

Considering the high incidence of AS in the general population (0.1%–0.5%), it is necessary to further explore the relationship between AS and glaucoma in future studies.

Two-sample MR suggests that AS is related to a higher risk of both POAG [odds ratio (OR): 1.28, 95% confidence interval (CI) 1.13–1.44; p = 1.1 × 10−4] and PACG (OR: 1.55, 95% CI: 1.09–2.09, p = 1.4 × 10−2). 

Multivariable MR shows a similar trend of the effect of AS on POAG (OR: 1.52, 95% CI: 1.22–1.90, p = 1.9 × 10−4) and PACG (OR: 2.05, 95% CI: 1.06–3.95, p = 3.2 × 10−2). 

However, no significant association was observed between the other five rheumatic diseases and glaucoma.

Therefore, AS is related to an increased risk of POAG and PACG, and the importance of glaucoma screening in these patients cannot be stressed enough.

Meng Y, Tan Z, Su Y, Li L, Chen C. Causal association between common rheumatic diseases and glaucoma: a Mendelian randomization study. Front Immunol. 2023 Sep 19;14:1227138. doi: 10.3389/fimmu.2023.1227138. PMID: 37799717; PMCID: PMC10550209.

2. However, Kim et al, conducted a cohort study of 10245 older Korean adults risk-set matched using propensity score, and reported patients with RA were more likely than matched controls to subsequently develop POAG, with hazard ratios ranging from 1.44 to 2.12.

These findings suggest that RA is associated with subsequent development of glaucoma. The role of an immune-mediated common pathophysiological pathway warrants further investigation.

Kim SH, Jeong SH, Kim H, Park E, Jang S. Development of Open-Angle Glaucoma in Adults With Seropositive Rheumatoid Arthritis in Korea. JAMA Netw Open. 2022;5(3):e223345. doi:10.1001/jamanetworkopen.2022.3345.

3. Teng used a two-sample Mendelian MR analysis to investigate the causal associations between RA, cataract and glaucoma in European and East Asian populations. Results revealed that RA had an increased risk of cataract (OR = 1.041, 95% CI = 1.019–1.064; P = 2.08×10−4) and glaucoma (OR = 1.029, 95% CI = 1.003–1.057; P = 2.94×10−2).

The authors concluded that oxidative stress and local inflammation are responsible for these causal associations.

Teng M, Wang J, Su X, Tian Y, Wang J, Zhang Y (2024) Causal associations between rheumatoid arthritis, cataract and glaucoma in European and East Asian populations: A bidirectional two-sample mendelian randomization study. PLoS ONE 19(3): e0299192. doi:10.1371/journal.pone.0299192.

Glaucoma and rheumatoid diseases appear to have some common pathogenetic pathways, such as inflammation and immunity. Theoretically, there is a significant association between the two conditions. However, studies have not conclusively shown the level of commonality between the two. Further research is required to reach a verdict on their association.

NANOPHTHALMOS

Nanophthalmos is a heritable condition characterized by a small, but structurally normal eye, with resultant high hyperopia (+8D to +25D). Defining features of nanophthalmos include a short axial length (less than 20-21 mm), with a proportional decrease in anterior segment dimensions, i.e., corneal diameter and anterior chamber depth. Despite a reduction in global ocular volume, the eye contains a normal sized lens.

Nanophthalmos is usually a sporadic disorder. Six major genes have been implicated in isolated nanophthalmos, including MFRP, PRSS56, BEST1, TMEM98, CRB1, and MYRF . For two of these genes (TMEM98, MYRF), the trait is inherited in an autosomal dominant manner, while the remaining genes cause recessive disease (MFRP, PRSS56, BEST1, CRB1). Additionally, several genes have been associated with nanophthalmos as part of a multisystem syndrome, including MYRF and FAM111A. 

Nanophthalmos may present as an isolated disorder or be part of a syndrome. These syndromes include: “nanophthalmos, retinitis pigmentosa, foveoschisis and optic drusen syndrome”, “oculo-dento-digital syndrome (ODD syndrome)”, “autosomal dominant vitreoretinochoroidopathy with nanophthalmos (ADVIRC)”and “Kenny-Caffey syndrome”.

Defining the genetic etiology is important for patient counseling and management since the different genetic causes are associated with varying ocular and systemic features. Glaucoma and other ocular complications secondary to nanophthalmos may be difficult to manage and genetic diagnosis can be helpful for early recognition.  

Nanophthalmos is frequently associated with ocular complications, presenting as high hyperopia with amblyopia and partially accommodative esotropia in early childhood. Given the anterior segment structure, patients are predisposed to angle closure and the resulting angle closure glaucoma, and often need cataract surgery early in life. Many cases of nanophthalmos complicate with uveal effusion with or without exudative retinal detachment. This is attributed to blockage of outflow from the vortex venous system secondary to a thickened sclera.

On distant direct ophthalmoscopic examination or indirect ophthalmoscopy without using a lens, a peculiar glow can be seen and the retinal vessels may be visible. Prominent iris convexity and impending angle closure with peripheral anterior synechiae (that may eventually form) may be observed beyond the fourth decade.

Diagnosis and monitoring for glaucoma in nanophthalmos are rather difficult due to a small disc, where even a small cup may be a sign of glaucoma. Additionally, visual field testing can be inaccurate because many patients have high plus lenses and reduced BCVA. In these cases SD OCT may detect subtle wedge-shaped loss of nerve fiber layer. HRT may assist in monitoring the deterioration of disc parameters. Stereo fundus photos can offer reliable documentation of disc morphology. These patients are also predisposed to malignant glaucoma.

Histology shows all three scleral layers have abnormal collagen fibrils that are frayed and split. The frayed fibrils contribute to scleral inelasticity which causes sequestration of extracellular fluid and consequently choroidal congestion, choroidal detachment, and/or exudative retinal detachment.

Vision loss may also result from other associated retinal findings, including foveal hypoplasia, optic disc drusen, retinoschisis and foveoschisis, retinitis pigmentosa, chorioretinal folds, or central retinal vein occlusions, or complications from ocular surgery. 

An important condition in the differential diagnosis of nanophthalmos is posterior microphthalmos. In posterior microphthalmos, anterior segment parameters are normal or slightly smaller though the axial length is small and the refraction is hyperopic. The posterior segment commonly shows reduction of capillary free zone, crowded optic disc, elevated papillomacular fold, chorioretinal folds, fine retinal folds, uveal effusion syndrome, pigmentary retinopathy and sclerochoroidal thickening on ultrasound.

Correction of the hyperopia with glasses that resemble aphakic spectacles usually results in moderate to good visual acuities. Contact lenses are a better cosmetic alternative. Strabismus surgery can be attempted, but the eyes are usually situated deep in the orbit and difficult to operate. The expansion of the orbital socket can be guided by the axial length of the eye. If the axial length is < 16 mm, the orbital growth is likely to be reduced resulting in facial asymmetries. 

Glaucoma is poorly responsive to medications. It can be managed by peripheral iridotomy or peripheral iridoplasty. However, the management of angle closure in nanophthalmos patients is primarily by lens extraction, but complications can occur in up to 40–60% of cases. Intraoperative and post-operative risks include increased rates of corneal endothelial damage, capsular rupture and vitreous loss, intraoperative aqueous misdirection, uveal effusion syndrome, and cystoid macular edema. Prophylactic scleral windows may reduce the rate of complication, owing to a thickened sclera and choroid that may predispose these conditions. 

While genetic therapies for nanophthalmos have not yet reached the clinical realm, there is some promise for gene replacement strategies for MFRP based on animal models.

UVEITIS GLAUCOMA HYPHEMA (UGH) SYNDROME

Uveitis-Glaucoma-Hyphema (UGH) Syndrome or Ellingson syndrome is a complication of intraocular lens (IOL) and MIGS implants, caused by mechanical irritation of intraocular structures.

The term UGH Syndrome was first coined by Ellingson in 1978. He noticed that certain styles of anterior chamber intraocular lenses (ACIOL) had warped footplates leading to a rocking motion of the lens and mechanical irritation of adjacent anterior chamber angle structures. 

Usually seen with ACIOLs, it is also seen with posterior chamber IOLs placed in the sulcus, causing posterior iris chafing by the loop or the optic. The syndrome occurs more commonly with planar loop design than with angulated loops. There is a report with scleral fixated lens also.

Repetitive mechanical trauma and chaffing of intraocular structures leads to a spectrum of iris transillumination defects and pigmentary dispersion to microhyphemas and hyphemas with elevated intraocular pressure (IOP).

It is characterized by chronic inflammation, cystoid macular edema (CME), secondary iris neovascularization, recurrent hyphemas, and glaucomatous optic neuropathy leading to a loss of vision. 

Inflammatory changes in the anterior chamber affect the aqueous outflow out of the eye, causing IOP to rise and cause glaucoma.

Hyphema complicates matters since blood in the anterior chamber may obstruct outflow channels and exacerbate inflammation.

The best treatment for a specific case of UGH syndrome depends on the exact underlying cause of the condition, and as such is variable.

Advances in IOL material and design as well as surgical technique have reduced the incidence of UGH syndrome from 3% to between 0.4% and 1.2%, but it remains a relevant clinical entity, particularly in eyes with a malpositioned IOL optic or haptics, zonular instability, and plateau iris configuration.

Chief complaints include intermittent blurry vision, “white out” vision, photophobia, hyperemia, and ocular pain or discomfort that may be out of proportion with examination findings.

Slitlamp examination can reveal the anterior chamber flare and cells. Usually it is mild but can occasionally lead to hypopyon formation. Slitlamp examination and gonioscopy can show microhyphema and hyphema. 

Ultrasound biomicroscopy (UBM) is the best technique for evaluation of such cases. UBM can confirm the proper location of an IOL’s haptics and optic, a tilted optic, or the haptic of a one-piece IOL improperly placed in the ciliary sulcus.

Management of UGH depends upon the situation. In mild cases pharmacological methods might be attempted. However, in most cases explantation of IOL is required.

GRANT'S SYNDROME

Grant's syndrome is a rare cause of secondary glaucoma.The syndrome was first described, and named, by Chandler and Grant in 1968. So far, only 16 primary cases have been reported. Two other cases have occurred after argon laser trabeculoplasty and intravitreal injection of bevacizumab and ranibizumab. 

The underlying mechanism for elevated intraocular pressure in these patients is apparently similar to that of other uveitic open-angle glaucomas – namely trabecular swelling, trabecular obstruction with cell/debris, and/or trabecular hyalinization.

Most of the cases have been Caucasians or blacks. Wei has reported one Asian patient with Grant's syndrome.

Patients, often >50 years old, present with high IOP (30-70 mmHg), frequently in both eyes (86% of cases). There is a female predominance in most cases (79%).

Characteristically there are yellowish trabecular meshwork (TM) precipitates with or without light anterior chamber flare and cells. Often, the TM precipitates are the only sign of inflammation. As other inflammatory signs usually were absent or minimal, it is easy to be misdiagnosed as primary open angle glaucoma (POAG).

Black arrow= PAS; White arrow= precipitates

The syndrome is diagnosed based on clinical manifestations. 

A few systemic conditions such as Sarcoidosis, rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been reported to be associated with Grant's syndrome. Scleritis, chronic uveitis and Posner-Schlossman syndrome (PSS) have also been reported to accompany Grant's syndrome. However, these diseases usually have other obvious inflammation signs, such as ciliary congestion, anterior chamber cells, and keratic precipitates.

Typical gonioscopic findings in Grant's syndrome are TM precipitates and scattered irregular peripheral anterior synechiae (PAS). Long-standing TM precipitates can prompt development of PAS. So, patients can be misdiagnosed with primary angle-closure glaucoma (PACG), especially those patients with a shallow anterior chamber. In PACG, PAS first appear superiorly and nasally, whereas inflammatory PAS are observed in areas where TM precipitates have been present and tend to distribute in all segments of the chamber angle.

Ultrasound biomicroscopy showing precipitates 

The patients typically do not respond well to anti-glaucoma treatment. However, the condition usually resolves with corticosteroid treatment.

The condition is prone to recurrence; up to 64% of cases may have recurrence of glaucoma in long-term follow-up.

Prognosis is usually good if treated promptly, the inflammation and pressure can be controlled, but regular follow-up is necessary due to the potential for recurrences.