LIGHT-ACTIVATED LIPOSOMES FOR GLAUCOMA

 

Biomedical researchers at Binghamton University in the USA, have developed a mechanism for drug-carrying liposomes that can be activated in the eye using near-infrared light.

The remotely triggered on-demand liposomal delivery system has been studied to treat glaucomatous neurodegeneration in mice.

The researchers overcame some difficulties in their drug delivery mechanism. “The first problem we found is that most pharmacological compounds are hydrophobic, which means they have low water solubility,” Wang said. “The second problem is using a thermal effect to trigger the release — how do we do that without affecting a patient’s comfort or having side effects?”

The scientists utilized the localized surface plasmon resonance (LSPR) effect of gold nanorods (AuNRs) under near-infrared (NIR) light (808 nm) to control the release of cyclodextrin-encapsulated melatonin from thermally responsive liposomal nanocarriers in the vitreous humor.

The liposomes—which are small, spherical, artificial vesicles that can deliver drugs and other molecules to specific sites in the body—have the gold nanorods embedded on their fatty surface. The gold heats up under a specific near-infrared wavelength and breaks down the membrane to release the needed medication, which is mixed with cyclodextrin to aid its absorption into the eye.

Due to the transparency of the eye's cornea, NIR light can penetrate deep tissues, enabling on-demand drug delivery to the retina.

By enhancing the drug's solubility and stability through cyclodextrin encapsulation, this remotely activated melatonin/HPβCD AuNRs liposomes delivery system can decrease intraocular pressure (IOP) elevation by (24 ± 7)%, enhance the survival rate of RGCs by (77 ± 6)%, and decrease glial fibrillary acidic protein (GFAP) activation by (75 ± 6)% at depth in an acute experimental glaucoma model.

This NIR-triggered drug delivery system presents the potential of a promising minimally photo-triggered therapeutic option for glaucoma treatment.

The scientists call it a minimally-invasive procedure, as they claim that the patient will need only a one-time injection that will be sufficient to lower the IOP.

REFERENCE:
Matuwana D, Hong E, Huang S, Xu X, Jang G, Xiao R, Rao S, Wang Q. Near-infrared activated liposomes for neuroprotection in glaucoma. J Mater Chem B. 2024 Oct 30;12(42):10902-10914. doi: 10.1039/d4tb00745j. PMID: 39355895.

IBN AL-NAFIS

 

ʿAlāʾ al-Dīn Abū al-Ḥasan ʿAlī ibn Abī Ḥazm al-Qarashī, better known as Ibn al-Nafīs, is regarded as: 

• the "father of circulatory physiology"
• the “greatest physician of his time”
• the “greatest physiologist of the Middle Ages”
• the “author of the largest encyclopedia by a single person”
• mentioned by some historians as the “second Ibn Sina”

He was the first person to challenge the long-held contention of the Galen School that blood could pass through the cardiac interventricular septum, and in keeping with this he believed that all the blood that reached the left ventricle passed through the lung. He also stated that there must be small communications or pores (manafidh in Arabic) between the pulmonary artery and vein, a prediction that preceded by 400 years the discovery of the pulmonary capillaries by Marcello Malpighi. 

He was one of the many Arab polymaths, that is scholars who worked in a large number of different areas. It is presumed that Al-Nafis wrote more than 110 volumes of medical textbooks.

Ibn al-Nafis was born around 1210-1213 in Karashia, a village near Damascus. He studied theology, philosophy, and literature. At the age of 16, he went to Nuri Hospital in Damascus and studied medicine there for 10 years. At the age of 23, he was invited to Egypt by the Ayyubid Sultan Al-Kamil. There, he was appointed as the chief physician at al-Naseri Hospital. He also taught jurisprudence at Al-Masruriyya Madarsa. He passed away in Cairo on 17th December 1288.

Among the various treatises written by Ibn al-Nafis, the most voluminous is the Al-Shamil fi Al-Tibb (The Comprehensive Book on Medicine). It was planned as a 300-volume encyclopedia, however, only 80 volumes could be completed by Ibn al-Nafis. It is one of the largest medical encyclopedias ever written by one person, and it gave a complete summary of the medical knowledge in the Islamic world at the time. His most famous treatise is regarded as the Sharh Tashrih al-Qanun ("Commentary on Anatomy in Books I and II of Ibn Sina's Kitab al-Qanun"), which he wrote at the age of 29 years.

The opening page of a book on medicine by Ibn al-Nafis

He also wrote a book on ophthalmology titled “al-Muhaḏḏab fī al-Kuhl” (“Polished Book on ophthalmology”); an original book on ophthalmology. Ibn al-Nafis wrote this book to polish and build on the concepts of ophthalmology originally made by Masawaiyh and Ibn Ishaq.

REFERENCES:

• West JB. Ibn al-Nafis, the pulmonary circulation, and the Islamic Golden Age. J Appl Physiol (1985). 2008 Dec;105(6):1877-80. doi: 10.1152/japplphysiol.91171.2008. Epub 2008 Oct 9. PMID: 18845773; PMCID: PMC2612469.

• Light From the East: How the Science of Medieval Islam Helped to Shape the Western World, John Freely.
• Galileo Goes to Jail and Other Myths about Science and Religion, Edited by Ronald L. Numbers.
• Feucht, Cynthia; Greydanus, Donald E.; Merrick, Joav; Patel, Dilip R.; Omar, Hatim A. (2012). Pharmacotherapeutics in Medical Disorders. Walter de Gruyter. p. 2. ISBN 978-3-11-027636-7.
• Moore, Lisa Jean; Casper, Monica J. (2014). The Body: Social and Cultural Dissections. Routledge. p. 124. ISBN 978-1-136-77172-9.

BIO-INTERVENTIONAL CYCLODIALYSIS AND SCLERAL REINFORCEMENT

 

Iantrek, a company based in the USA, has developed a bio-interventional cyclodialysis and scleral reinforcement procedure. It is being used in open-angle glaucoma (OAG) patients undergoing cataract surgery. 

CYCLO-PEN

SCAFFOLD IMPLANTATION

An ab-interno approach is used to create a sectoral cyclodialysis in OAG patients. Subsequently, visco-cycloplasty with scleral reinforcement using a homologous minimally modified allograft scaffold is performed to maintain the patency of the cyclodialysis reservoir and increase uveoscleral outflow.

From a mechanistic standpoint, cyclodialysis has a dual mechanism of IOP lowering, through increased uveoscleral outflow as well as reduction in aqueous production from the detached ciliary body.

Bio-reinforced cyclodialysis technique uses adjunct allogeneic scleral tissue scaffolding as reinforcement to prevent the premature closure of the cyclodialysis intervention by maintaining a permanent uveoscleral conduit for aqueous outflow. An internal uveoscleral filtration reservoir is thus supported by the allogeneic bio-scaffold, which acts as a biologic non-absorbable spacer between the ciliary body and the adjacent scleral wall.

The CREST clinical study is a real-world evidence registry in which patients are followed prospectively through 24 months after undergoing cyclodialysis intervention. The results of a multi-center study involving 12 surgeons from the CREST US and OUS clinical studies have been published recently.

As per the results of the study, successful cyclodialysis and allograft bio-scaffold reinforcement was achieved in 117 eyes.

At baseline, mean BCVA was 0.48 (95% CI: 0.42‒0.54; 20/40 Snellen), and mean ± SD medicated IOP was 20.2 ± 6.0 mmHg on 1.4 ± 1.3 IOP-lowering medications.

At 12 months, there was a 27.1% reduction from baseline mean medicated IOP. In eyes with medicated baseline IOP > 21 mmHg (n = 45), there was a 39.7% paired IOP reduction at 12 months with a concurrent reduction in the mean number of IOP lowering medications to 0.8 ± 0.9 which was statistically significant (p < 0.01).

81.9% of eyes achieved a medicated IOP ≤ 18 mmHg with no increase in medications at 12 months.

Complications included minimal blood reflux from the cyclodialysis cleft, which was not associated with any significant postoperative hyphema, transient hypotony occurred in one eye, three patients who underwent concurrent phaco surgery developed cystoid macular edema,

Secondary glaucoma surgery such as Selective Laser Trabeculoplasty (SLT), Ahmed Valve or Xen-gel implantation, and cyclophotocoagulation was performed in 3.2% of the cases.

REFERENCE:

Ianchulev T, Weinreb RN, Calvo EA, Lewis J, Kamthan G, Sheybani A, Rhee DJ, Ahmed IK. Bio-Interventional Cyclodialysis and Allograft Scleral Reinforcement for Uveoscleral Outflow Enhancement in Open-Angle Glaucoma Patients: One-Year Clinical Outcomes. Clin Ophthalmol. 2024;18:3605-3614. https://doi.org/10.2147/OPTH.S496631.

FOR COMPANY DETAILS PLEASE CLICK THE LINK BELOW:

https://iantrekmed.com/

 

ROLE OF ETHNICITY IN GLAUCOMA

 

Glaucoma is globally more prevalent among the Black population, compared with white patients, develops 10 years earlier on average, and is 15 times more likely to cause visual impairment. The outcomes of medical and surgical treatment for glaucoma are worse for black than white populations.

An observational study was performed in the UK to assess whether patients from minority ethnic groups have different perceptions about the quality-of-life (QOL) outcomes that matter most to them.

The study involved 511 patients diagnosed with primary open-angle glaucoma and ocular hypertension.

The self-reported priorities for health outcomes among the responders was divided into:

(1) vision, (2) drop freedom, (3) intraocular pressure (IOP), and (4) one-time treatment.

For White patients, the priority for QOL was good vision.

However, for Black/Black British patients the priority was drop freedom, followed by control of IOP and finally the possibility of one-time treatment.  

For Asian/Asian British patients, the priority was control of IOP. This was almost the same as the priority for vision.

Other ethnic minority groups also had higher odds ratios (ORs) for prioritizing health outcomes other than vision alone: 4.50 (1.03 to 19.63, p=0.045) for drop freedom and 5.37 (1.47 to 19.60, p=0.011) for IOP.

The study showed that ethnicity is strongly associated with differing perceptions regarding health outcomes and QOL priority. Therefore, an individualized and ethnically inclusive approach is needed when selecting and evaluating treatments in clinical and research settings.

Certain important implications from this study include the fact that the patient’s priority for care may not be the same as the treating physician. A large number of patients in this study regarded freedom from drops as the most important priority. This implies that minimally-invasive glaucoma surgeries (MIGS) and laser procedures such as selective laser trabeculoplasty (SLT) could be a useful approach in making the patient drop-free. Therefore, non-white patients could be more perceptive for such procedures.

It also shows that black patients may not use their eye drops regularly, causing detrimental outcomes.

Furthermore, QoL outcomes from studies which predominantly recruit certain ethnic groups may not be generalizable to other ethnic groups. This requires a tailored-approach to perform QOL studies.

In conclusion, ethnicity plays a major role in the occurrence of glaucoma, the management profile, and the perceptions of patients across various ethnicities.

REFERENCE:

Safitri A, Konstantakopoulou E, Gazzard G, et al. Priorities for health outcomes in glaucoma in an ethnically diverse UK cohort: an observational study. BMJ Open 2024;14:e081998. doi:10.1136/ bmjopen-2023-081998

A 1938 ARTICLE ON PATHOGENESIS OF GLAUCOMA

 

A wonderfully elaborate article was published in 1938 by Elwyn regarding the pathogenesis of chronic simple glaucoma (primary open-angle glaucoma).

According to him, intraocular pressure (IOP) depends on the tension exerted on the sclera by the intraocular structures. These structures include the sclera, the iridocorneal angle, the ciliary body, the vitreous, and the choroid.

The theories regarding the causation of glaucoma can be classified as follows:

1. Retention theories, based on a hindrance to the elimination of the aqueous
2. Theory based on an increase in the production of aqueous
3. Theory based on an increase in the volume of one or more of the intraocular structures

RETENTION THEORIES:

Retention due to a change in the sclera:

According to this theory, the sclera loses its elasticity and shrinks, and that affects the normal outflow of the aqueous out of the eye. The loss of elasticity is either due to a senile change or to the sequence of inflammatory changes.

Retention of aqueous in the eye due to block at the iridocorneal angle:

1. This can happen due to pressure of the iris against the angle. It can occur from inflammatory changes in the anterior segment of the eye followed by adhesions between the iris and the cornea;
2. It can also occur from deposits of pigment in the pectinate ligament
3. Or due to primary sclerosis of the pectinate ligament

Retention can also occur due to blocking of the aqueous outflow in the iris as a result of a deposit of pigment or from degenerative changes.

THEORY BASED ON AN INCREASE IN THE PRODUCTION OF AQUEOUS:

An increase in the production of aqueous has been assumed to be due to disturbances in innervation and to inflammatory and degenerative causes.

THEORY BASED ON AN INCREASE IN THE VOLUME OF THE INTRA-OCULAR STRUCTURES:

Vitreous:

The vitreous, behaves as a colloid, and swells when it is turned acidic. It is presumed in glaucoma the vitreous changes towards the acidic side. That causes it to swell and increases IOP.

Some investigations have shown that normally the pH of the vitreous is around 7.5 to 7.6. A change in the reaction toward the acidic side causes a diminution in the volume of the vitreous until the isoelectric point, which is 4.2, is reached. The contrary has been assumed by others, that is, that the vitreous becomes more alkaline and swells.

Under normal conditions the vitreous in the living eye is at its maximum turgescence.

Choroid:

The choroid is a highly vascular membrane that can easily change its thickness by varying its blood content. Obstruction of the vortex veins occurs owing to kinking of the veins at the sinus or due to endophlebitic or sclerotic processes in the veins. Relaxation of the vasomotor mechanism causes a relaxation of the uveal vessels and an increase in the blood content of the eye.

Several local and general factors play a role in the etiology of glaucoma, including disturbances in the regulation of the intraocular vascular apparatus which cause changes in the circulation and the exchange of fluid between blood and tissues.

A close study of these theories brings the conviction that they are insufficient to explain the pathogenesis of glaucoma.

Some authors, like Thiel, hint at a disturbance in regulation, at a multiplicity of factors, and at a relation to the endocrine and sympathetic nervous systems in a vague sort of way. However, no definite theory which is based on a disturbance in regulation has so far been advanced.

ASSOCIATION OF RHEUMATOID ARTHRITIS WITH GLAUCOMA

 

Rheumatoid arthritis (RA) is a progressive, inflammatory, autoimmune disease. Several factors, including autoantibodies, immune complexes, T cell-mediated antigen-specific responses, and T cell-independent cytokine networks, are involved in the pathogenesis of RA.

There is evidence of immunological mechanisms in the development and progression of primary open-angle glaucoma (POAG). Autoantibodies and CD4+ T cells involved in the pathogenesis of RA are also observed in patients with POAG. Similarly, there is enhanced expression of Heat-Shock protein (HSP) in glaucoma patients. Another indirect evidence comes from the use of etanercept, a tumor necrosis factor–α inhibitor used to control RA progression, reduced retinal ganglion cell (RGC) loss by approximately 50% in a rat glaucoma model.

However, there is limited evidence connecting RA, the most common autoimmune disease, with the risk of developing POAG.

Kim and colleagues conducted a nationwide propensity-matched cohort study using data from the Korean National Health Insurance Service-Senior cohort from 2002 to 2013. Data analysis was performed from November 2020 to July 2021.

A total of 2049 patients with incident seropositive RA and 8196 time-dependent, propensity score–matched, risk-set controls were included.

The cumulative incidence of POAG was higher in the RA cohort than in the matched cohort during the entire follow-up period. The 2-year cumulative incidence risk of POAG was 2.36% in the RA cohort and 1.28% in the matched-control cohort; the 4-year cumulative incidence risk was 4.29% in the RA cohort and 2.64% in the matched control cohort.

POAG developed in 86 of 2049 patients with RA and 254 of 8196 matched controls.

In the RA cohort, the incidence rate of POAG was 981.8 cases per 100 000 person years (95% CI, 794.3-1213.7 cases per 100 000 person years), whereas in the matched controls, the incidence rate was 679.5 cases per 100 000 person years (95% CI, 600.8- 768.3 cases per 100 000 person years).

Patients with RA were more likely to develop POAG than the matched controls (hazard ratio [HR], 1.44; 95% CI, 1.13-1.84). Increased POAG risk in the RA cohort was predominantly observed 2 years into the follow-up period (HR, 1.83; 95% CI, 1.28-2.61) and in those aged 75 years or older (HR, 2.12; 95% CI, 1.34-3.35).

These findings suggest that RA is associated with a higher risk of developing POAG, especially within 2 years after diagnosis or among patients aged 75 years or older.

When considered collectively, it is reasonable to suspect that RA and POAG share common pathogenic pathways, including autoimmune components.

REFERENCE:

Kim SH, Jeong SH, Kim H, Park EC, Jang SY. Development of Open-Angle Glaucoma in Adults With Seropositive Rheumatoid Arthritis in Korea. JAMA Netw Open. 2022 Mar 1;5(3):e223345. doi: 10.1001/jamanetworkopen.2022.3345.

GENES ASSOCIATED WITH GLAUCOMA

 

DEUBIQUITINATING ENZYME INHIBITORS AND NEUROPROTECTION

 

Deubiquitinating enzyme (DUB) inhibitors are promising pharmacological interventions for neurodegenerative disorders.

A study by Hu et al has demonstrated that the pan-DUB inhibitor PR-619 has a neuroprotective effect on retinal ganglion cells (RGCs).

PR-619 exerts various biological functions including, induction of autophagy, anti-apoptotic effects, and antitumor properties.

In the experimental glaucoma model of the study, impaired mitophagy was seen in the RGCs.

Parkin is an intricately multifunctional member of the E3 ubiquitin ligase family. It mediates the selective elimination of impaired mitochondria through mitophagy. When mitochondria lose membrane potential, indicating dysfunction or damage, parkin activation and accumulation facilitate mitophagy.

Parkin exerts its ubiquitin-tagging effect upon several proteins present within the mitochondrial outer membrane. These ubiquitinated proteins, bearing Parkin's molecular insignia, serve as beacons of recognition for a host of autophagy receptors and adaptors, among which optineurin emerges as a prominent player.

Evidence shows activated parkin-mediated mitophagy reduces neuronal apoptosis in Parkinson’s and Alzheimer’s diseases.

Dysfunctional mitophagy plays a role in glaucoma pathogenesis.

In vivo, PR-619 increased RGC survival in glaucomatous rats. In vitro, protected RGCs against excitotoxicity and reduced ubiquitin-specific protease (USP) 15 expression.

Additionally, PR-619 upregulated parkin expression, increased LC3-II/LC3-I ratios, and elevated LAMP1 levels, indicating enhanced mitophagy in vivo and in vitro.

Moreover, numbers of mitophagosomes were increased in the optic nerves of PR-619-treated ocular hypertensive rats in vivo.

Prior investigations have substantiated that PR-619 confers neuroprotection to RGCs challenged with glutamate excitotoxicity by augmenting parkin-dependent mitophagy.

Therefore, PR-619 could be a useful strategy for saving RGCs in glaucoma patients.

REFERENCE:

Hu X, Zhang J, Ma H, Lian W, Song W, Du C, Chen S, Wang D, Wei J, Lu Q. The broad-spectrum deubiquitinating enzyme inhibitor PR-619 protects retinal ganglion cell and augments parkin-mediated mitophagy in experimental glaucoma. Sci Rep. 2024;14:24654.

Sirt6; ANTI-AGING; GLAUCOMA

Glaucoma is characterized by progressive loss of retinal ganglion cells (RGCs).

The loss of RGCs also occurs as an age-dependent process.

Several regulatory factors, that could impact glaucoma and aging, have been studied in animal models.

Sirtuins (Sirts) belong to a widely preserved protein family.

They resemble the yeast Sir2 protein, which operates as a NAD-dependent histone deacetylase, prolonging the yeast’s lifespan.

The anti-aging protein, Sirt6, is highly expressed in RGCs.

It is essential in protecting RGCs from the effects of aging and glaucoma.

In mouse models of high-tension glaucoma, the Sirt6 level was decreased after IOP elevation.

Deleting Sirt6 globally or specifically in RGCs led to progressive RGC loss and optic nerve degeneration during aging, despite normal intraocular pressure (IOP), resembling a phenotype of normal-tension glaucoma.

Genetic overexpression of Sirt6 globally or specifically in RGCs significantly attenuated high tension-induced degeneration of RGCs and their axons.

The study shows the critical role of Sirt6 in preventing RGC and optic nerve degeneration during aging and glaucoma.

Wenbo Zhang, a co-author and Professor of Ophthalmology at the University of Texas, was quoted as saying "Therapeutically targeting Sirt6 offers a promising new avenue for glaucoma treatment, especially for cases that do not respond to traditional treatments aimed at reducing eye pressure". He added, "This could be a game-changer in how we approach this disease." 

REFERENCE:

Xia F, Shi S, Palacios E, Liu W, Buscho SE, Li J, Huang S, Vizzeri G, Dong XC, Motamedi M, Zhang W, Liu H. Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma. Mol Ther. 2024 Jun 5;32(6):1760-1778. doi: 10.1016/j.ymthe.2024.04.030. Epub 2024 Apr 24. PMID: 38659223; PMCID: PMC11184404.

GLAUCOMA FOLLOWING INFANTILE CATARACT SURGERY

 

Cataract surgery, especially infantile cataract surgery, is associated with a higher incidence of glaucoma post-operatively.

Choe et al have identified the risk factors for incisional glaucoma surgery following infantile cataract (IC) surgery.

The population-based cohort study was conducted using the Korean National Health claims database, among Korean children born between 2002 and 2018.

650 patients had undergone IC surgery with a mean (standard deviation [SD]) follow-up period of 6.2 (3.2) years.

92 (14.2%) were diagnosed with glaucoma following infantile cataract surgery (GFICS).

Among them, 21 patients (22.8%) underwent incisional glaucoma surgery after a mean (SD) follow-up duration of 5.4 (2.8) years from the diagnosis of GFICS.

Of the 21 GFICS patients who underwent incisional glaucoma surgery, the median (IQR) age at incisional glaucoma surgery was 4 years. Among them, 10 patients underwent trabeculectomy (TLE), 10 underwent glaucoma drainage implant (GDI) surgery, and one underwent both TLE and GDI surgery.

The risk factors for developing GFICS include young age at IC surgery, microphthalmia, aphakia, and usage of trypan blue during surgery.

However, the Infant Aphakia Treatment Study (IATS) randomized clinical trial (RCT) identified similar risks of GFICS in both aphakia and pseudophakia groups.

In the multivariable analysis, genetic, metabolic, infectious comorbidities, and ophthalmic anomalies were not associated with the risk of undergoing incisional glaucoma surgery.

Likewise, factors associated with IC (i.e., age at IC diagnosis, age at IC surgery, type of IC surgery, and location of IC surgery institution) also were not associated with the risk of incisional glaucoma surgery.

However, younger age at diagnosis of GFICS was the only risk factor associated with subsequent incisional glaucoma surgery (P = 0.03).

REFERENCE:

Choe, S., Kim, Y.K. & Ha, A. Nationwide incidence of and risk factors for undergoing incisional glaucoma surgery following infantile cataract surgery. Sci Rep 14, 16286 (2024).

 

RISK FACTORS FOR UNDIAGNOSED GLAUCOMA

 

Undiagnosed glaucoma is a hidden, significant public health problem. Surveys have shown that almost 50%-90% of glaucoma cases are undiagnosed in a population.

Some risk factors associated with undiagnosed glaucomas include:

• Lower education levels
• Not consulting an ophthalmologist in the year prior to the diagnosis
• Being seen by an optometrist rather than an ophthalmologist

Features associated with undiagnosed glaucoma are:

• A smaller vertical cup-to-disc ratio (CDR)
• Negative family history of glaucoma
• Lower mean baseline intraocular pressure (IOP)
• Baseline hyperopia

In a study by Wong, the odds of having visual field defects among those with diagnosed glaucoma were lower than those with undiagnosed glaucoma (odds ratio [OR], 0.06; 95% confidence interval [95% CI], 0.01–0.69; P=0.02). In addition, the odds of undiagnosed glaucoma were 14 times higher (OR, 14.10; 95% CI, 2.83–7.08; P<0.0001) in participants with visual field defects compared with those without glaucoma. [1]

A study was performed by Chan et al, to examine the associations with previously undiagnosed primary open-angle glaucoma (POAG) in the European Prospective Investigation of Cancer (EPIC)-Norfolk Eye Study. [2]

30445 men and women aged 40–79 years were recruited in the baseline survey from the databases of 35 general practices. The predominant ethnicity of the cohort was white. Among the 314 POAG subjects, 160 of them had HTG and 154 had NTG; 207 (65.9%) were known cases, diagnosed before the start of the study and 107 (34.1%) were previously undiagnosed.

The study reported two factors associated with undiagnosed POAG:

• Lower IOP levels (OR 0.71/mm Hg, 95%CI 0.63 to 0.80, p<0.0001)
• Participants not reporting vision problems (OR 0.03, 95%CI 0.01 to 0.69, p<0.0001)

The first points to an over-reliance on the IOP level to exclude glaucoma in the community, leading to patients with lower IOP being missed.

This study demonstrates that it is easy for eye care providers to be reassured by an IOP level <24mmHg while other features of glaucoma are missed. It must be stressed therefore that among patients with non-elevated IOP, care should be taken to examine the optic disc carefully and with supportive disc imaging and visual field testing to improve the chances of identifying suspicious disc features.

In this study, other features of the severity of glaucoma such as vertical CDR and visual field mean deviation were not associated with missed OAG cases. It could be because CDR does not adequately capture features of a glaucomatous disc, and visual fields may not be done routinely at the optician. Even with advanced field defects, many patients with glaucoma are asymptomatic, so field defects will not necessarily provide a reason to visit the optician.

In conclusion, the most important healthcare implication from this analysis is to avoid being falsely reassured by a lower level of IOP in glaucoma case finding.

REFERENCES:

Wong EY, Keeffe JE, Rait JL, Vu HT, Le A, McCarty PhD C, Taylor HR. Detection of undiagnosed glaucoma by eye health professionals. Ophthalmology. 2004 Aug;111(8):1508-14. doi: 10.1016/j.ophtha.2004.01.029. PMID: 15288980.

Chan MPY, Khawaja AP, Broadway DC, Yip J, Luben R, Hayat S, Peto T, Khaw KT, Foster PJ. Risk factors for previously undiagnosed primary open-angle glaucoma: the EPIC-Norfolk Eye Study. Br J Ophthalmol. 2022 Dec;106(12):1684-1688. doi: 10.1136/bjophthalmol-2020-317718. Epub 2021 Jun 25. PMID: 34172506; PMCID: PMC9685696.

COMPLICATIONS OF GLAUCOMA DRAINAGE DEVICES (GDDs)

 

EARLY COMPLICATIONS

• EXCESSIVE HYPOTONIA
•  Induced by over-drainage of aqueous humor.
• Can lead to anterior chamber (AC) flattening with possible contact between endothelium and the silicone tube, choroidal effusion with detachment, hypotonic maculopathy, or supra-choroidal hemorrhage.
• Valved devices have less frequent early postop hypotonia.

• CHOROIDAL EFFUSION SYNDROME
• Choroidal detachment occurs in 10% to 20% of cases with classic GDDs.
• This can be avoided by implanting the GDD in the eye without inserting the tube in the AC. This allows a connective tissue capsule to develop around the plate in 6-8 weeks. In the second step, the tube is inserted into the AC.
• Alternatively, the tube is blocked by a non-absorbable or absorbable suture.
• However, slits in the silicone tube must be made to achieve some immediate filtration.
• In the case of pars plana implants temporary occlusion of the tube can be done by gas tamponade in the vitreous.

• SUPRA-CHOROIDAL HEMORRHAGE
• Incidence of supra-choroidal hemorrhage after GDD implantation varies from 0 % to 6 %.
• Implants with an IOP-regulation mechanism or a drainage tube ligature have a better prognosis.
• Predisposing factors are hypotony, angle closure glaucoma, and multiple previous surgical events.
• Choroidal hemorrhage represents the greatest risk of reduced vision postoperatively.

• ENDOTHELIUM AND LENS
• Early postop-hypotonia causes shallowing/flattening of AC with a risk of the iris/lens touching the corneal endothelium.
• Consequently, the tube can touch the cornea or iris and get obstructed.

• MOTILITY DISORDERS
• Large implants and a large filtration bleb can affect the motility of the adjacent extraocular muscles.
• Adhesions between the capsule and muscle probably play a role.
• Diplopia can occur.
• In a prospective study, motility disturbances were noticed in 46% of patients after implantation of a double-plate Molteno GDD.
• The study also reported restriction of the superior rectus, Pseudo-Brown syndrome, and paralysis of the superior oblique. However, the diplopia usually regressed within one year.
• With 350-mm² and 500-mm² Baerveldt implants, 7 to 27% of patients had motility disorders, especially with the larger size implants.
• For smaller implants, such as the Ahmed Valve, the incidence is lesser, in the range of 2-3%.

• TRANSIENT HYPERTENSION
• Temporary hypertensive phase can occur in 80% of patients in the first three postop months.
• Occurs from an inflammatory response and fibrovascular scarring surrounding the GDD plate.
• This is a critical phase with the need for inflammatory agents and reduction in IOP since this stage is critical in long-term results.
• GDD implantation can be performed with Mitomycin-C to achieve better long-term results. However, some authors found higher rates of post-op hypotonia with it.

LATE COMPLICATIONS

• ENDOTHELIUM/CATARACT
• Iris, lens or the tube touching the corneal endothelium can cause endothelial loss. Therefore, there is a risk of corneal decompensation.
• Tube implantation through pars plana into the vitreous can be beneficial in post-keratoplasty patients, those with iridial angle anomalies or neovascularization of the iris, and phakic patients with shallow AC.
• Pars plana implantation requires total vitrectomy to prevent vitreous blocking the tube.
• Disadvantages of this method are the risk of retinal complications, the impossibility of visual examination of the tube in case of an apparent obstruction, and a higher risk of hypotonia.
• Induction or progression of cataracts is reported in 8% to 34% of phakic patients. However, the rates are comparable for trabeculectomy and classical glaucoma surgeries.

• EROSION OF THE CONJUNCTIVA
• The conjunctiva at the site of entrance of the tube into the AC, near the limbus is occasionally eroded, causing exposure of the tube.
• The tube should be covered with pericardium, scleral patch, dura, fascia lata, or implanted through a scleral tunnel.
• The risk of exposure of the tube or plate is reported to be between 1%-3%.
• This is a risk factor for endophthalmitis.

• DISLOCATION OF THE TUBE
• In 2-3% of patients tube may displace, causing insufficient filtration.
• Usually occurs from incorrect tube implantation.
• The end of the tube in the AC should be cut diagonally with the bevel facing the endothelium to prevent occlusion by the iris and subsequent displacement.

REFERENCE:

Hille K, Moustafa B, Hille A, Ruprecht KW. Drainage devices in glaucoma surgery. Klin Oczna. 2004;106(4-5):670-81. PMID: 15646493.

HISTORY OF MEDIEVAL OPHTHALMOLOGY

CREDIT TO THE ORIGINAL AUTHORS