WIRELESS MEASURING CONTACT LENS

 

Monitoring IOP is a useful method to obtain a continuous record of the glaucoma patient’s response to medications. In this regard smart contact lenses have been developed which monitor IOP constantly. However, these lenses have been found to be sensitive to environmental conditions, especially temperature fluctuations. Xiao and co-workers have developed an intelligent wireless measuring contact lens (WMCL) incorporating a dual inductor−capacitor−resistor (LCR) resonant system to achieve temperature self-compensation for quantitative IOP monitoring in different application environments.

The researchers designed two miniature spiral circuits, each with a unique natural vibration pattern that alters when stretched by minute amounts, such as with changes to an eye’s pressure and diameter. They sandwiched these tiny circuits between layers of polydimethylsiloxane, a commonly used contact lens material, to create pressure-detecting contact lenses. The two circuits enable the integration of low-frequency and high-frequency resonators within a single layer of a sensing circuit without causing visual impairment.  

Fluctuations in IOP can induce changes in the curvature of the contact lens. These changes lead to variations in the shape or position of the coil, subsequently causing changes in inductance and resulting in shifts in resonance frequency. Inductive IOP sensors integrate the sensor with the internal antenna, simplifying circuit design and reducing fabrication complexity and costs. The vibration patterns are sent wirelessly to a computer which monitors the IOP. The lens was found to be more sensitive in monitoring changes compared to other smart contact lenses.

The lenses have been tested in animal eyes and found to be effective in temperatures ranging from 12- to 50-Fahrenheit. According to the researchers, the linear combination of the dual resonators can eliminate the impact of temperature variations on measurement accuracy. The lenses were effective even when the internal temperature variations exceeded 10-degree centigrade.

The researchers claim that the WMCL has immense potential as the next generation of all-weather IOP monitoring devices.

REFERENCE:

Li X, Chen W, Li H, Shen B, He J, Gao H, Bin F, Li H, Xiao D. Temperature Self-Compensating Intelligent Wireless Measuring Contact Lens for Quantitative Intraocular Pressure Monitoring. ACS Appl Mater Interfaces. 2024 May 1;16(17):22522-22531. doi: 10.1021/acsami.4c02289. Epub 2024 Apr 23. PMID: 38651323.

IMMUNOLOGICAL BASIS OF GLAUCOMA

 

Experimental and clinical studies suggest a role of auto-immunity in the pathogenesis of glaucoma. A wide range of serum auto-antibodies especially against heat shock proteins (HSPs) and deposits of immunoglobins have been detected in glaucoma patients, as well as, animal models of glaucoma, pointing to an immunological mechanism for the causation of glaucoma.

It has been found that even transient intraocular pressure (IOP) elevation is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ganglion cell (RGC) degeneration that persists after IOP returns to a normal level.

A study found that inoculation of rats with human HSP27 and HSP60 induced an optic neuropathy that resembles glaucomatous neural damage, and elevated IOP has been reported to induce expression of HSPs in the retina, particularly in the RGCs. [1]

Therefore, an association of elevated IOP, HSP upregulation, and induction of anti-HSP autoimmune responses in glaucoma has been suggested.

A critical question is how autoimmune responses, such as those against HSPs, are induced in glaucoma? As HSPs are among the most highly conserved proteins from bacteria to mice to humans (up to 60% identity), a possibility is that the anti-HSP immune responses are induced originally by commensal bacterial HSPs, and are reactivated by host HSPs during glaucoma.

The fact that glaucoma patients exhibit increased titers of antibodies against Helicobacter pylori and that immunization with HSPs in rats induces glaucomatous neural damage are in line with this possibility. 

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Both bacterial and human HSPs are target antigens of T cells; retina-infiltrating T cells cross-react with human and bacterial HSPs. HSP-specific CD4+ T-cell responses and glaucomatous neurodegeneration are both abolished in mice raised in the absence of commensal microbial flora (germ-free (GF) mice), supporting a mechanism of commensal microflora sensitized T-cell responses underlying the pathogenesis of glaucoma.

Chen et al, have hypothesized that mice harbor memory T cells to bacterial HSPs that can be activated by host HSPs through molecular mimicry when the blood-retinal barrier is compromised by elevated IOP. Their study indicates a need for prior exposure to commensal microbial flora in the induction of both HSP-specific T-cell responses as well as RGC and axon loss following IOP elevation. [1]

HSP-specific T-cell responses probably contribute to normal-tension glaucoma (NTG) as HSP immunization elicits glaucomatous RGC loss in rats. Elevation of IOP upregulates membrane-bound and extracellular HSPs in the ganglion cell layer of the retina, subsequently leading to immune-mediated neural damage through activating HSP-specific CD4+ T cells, which are originally induced by microbial HSPs.

REFERENCE:

[1] Chen H, Cho KS, Vu THK, Shen CH, Kaur M, Chen G, Mathew R, McHam ML, Fazelat A, Lashkari K, Au NPB, Tse JKY, Li Y, Yu H, Yang L, Stein-Streilein J, Ma CHE, Woolf CJ, Whary MT, Jager MJ, Fox JG, Chen J, Chen DF. Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma. Nat Commun. 2018 Aug 10;9(1):3209. doi: 10.1038/s41467-018-05681-9. Erratum in: Nat Commun. 2018 Sep 20;9(1):3914. PMID: 30097565; PMCID: PMC6086830.

IOP rise in consensual eye after glaucoma surgery

 

A significant increase in IOP in the fellow eye (FE) after glaucoma surgery in the index eye (IE) has been noted by some researchers. Although, there are also reports of reduction in IOP in the FE after surgery in the IE.

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In a study performed on 187 consecutive glaucoma patients, who underwent either trabeculectomy or Ahmed Glaucoma Valve (AGV) implantation, it was found that nearly a third of them required medical or surgical management of IOP in the FE following surgery of the IE. [1]

In the study, 87.7% patients underwent trabeculectomy and 12.3% underwent AGV implantation.

Incidentally, in 84% of the patients the FE was already glaucomatous and 22 eyes had undergone trabeculectomy.

The mean IOP rise in FE among all patients (trabeculectomy and AGV), was as follows:

Pre-operative IOP in IE	17.6± 6.9 (n-187)
Pre-operative IOP in FE	14.48± 3.4 (n‑187)
IOP in FE: Post-op 1 day	14.54 ± 4.9 (p‑ 0.694)
Post-op 1 week	15.8 ± 5.5 (p‑0.005)
Post-op 1 month	15.62 ± 5.7 (p‑0.007)
Post-op 3 months	15.09 ± 5.0 (n‑135, p‑0.279)

 

Among patients with AGV shunt surgery (n=23), the mean fellow eye IOP was higher than baseline at all‑time points, with maximum rise on day 1 (15.91 ± 6.3, baseline 13.78 ± 2.7; n‑ 23, p‑0.066).

Pre‑operative acetazolamide (n=43) strongly predicted a statistically significant increase in FE mean IOP.

Among all patients, 15% required additional intervention to control IOP in the FE in the first 30 days and 33% in the first 90 days after glaucoma surgery in the IE.

In the trabeculectomy group, 35% patients required an increase in the anti-glaucoma medications or surgery in the FE, within 90 days of surgery in the IE.

In the AGV group, 18% patients required additional intervention in the FE within 90 days of surgery in the IE.

Among all patients, 14.4% eyes required surgical intervention in the FE.

Other studies have also noted a significant increase in IOP in the FE after glaucoma surgery. Meshksar reported maximum IOP rise 1 week after surgery [2], while Kaushik noted it at 6 weeks following surgery [3].

Incidentally, Kaushik did not report any significant association with acetazolamide.

A number of explanations have been surmised for this phenomenon. It is assumed that patients stop the anti-glaucoma medications in FE after surgery in one eye. 

Another potential explanation for the rise in IOP would be the sequelae of under-perfusion of the scleral meshwork due to preferential flow through the sclerostomy site. Under-perfusion results in meshwork densification, activation of endothelial cells and increase in extracellular matrix both in the ipsilateral and contralateral eye offering resistance to aqueous outflow and in turn contributing to the rise in consensual eye IOP. 

It has also been postulated that the scleral spur consists of special cells that play an important role in the afferent pathway of the reflex that controls bilateral ciliary body and meshwork contractile tone. Surgery in one eye could affect the other eye through these cells.

These studies indicate that close monitoring is required for the consensual eye after glaucoma surgery in one eye.

REFERENCE:

[1] Rajsrinivas D, Dubey S, Pegu J, Majumdar A. Consensual eye intra-ocular pressure rise following unilateral glaucoma surgery. Indian J Ophthalmol. 2023 Mar;71(3):873-879. doi: 10.4103/ijo.IJO_1909_22. PMID: 36872698; PMCID: PMC10230001.

[2] Meshksar A, Hajizadeh M, Sharifipour F, Yazdani S, Pakravan M, Kheiri B. Intraocular pressure changes in the contralateral eye after glaucoma surgery. J Glaucoma 2021;30:1074‑81.

[3] Kaushik S, Agarwal A, Kaur S, Lomi N, Raj S, Pandav SS. Change in intraocular pressure in the fellow eye after glaucoma surgery in 1 eye. J Glaucoma 2016;25:324–9.

SALIVA-BASED GENETIC TEST FOR GLAUCOMA

 

Researchers in Australia have devised a novel glaucoma polygenic risk score (PRS) that identifies those at high risk of losing their sight and prioritizes their treatment. The test performed on blood or saliva can detect the risk of glaucoma in 15-times more people, compared to other tests.

The lead researcher of the study, Associate Professor Owen Siggs, from the Flinders University, was quoted as saying that “Early diagnosis of glaucoma can lead to vision-saving treatment, and genetic information can potentially give us an edge in making early diagnoses, and better treatment decisions”. This can make genetic testing for glaucoma easier, and more commonly available early in the course of the disease.

The test is based on the premise that genetic variation is an increasingly powerful indicator in disease risk stratification. The study was performed to compare the polygenic and monogenic variants in risk of glaucoma.

The study involved 2507 individuals from the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) and 411337 individuals in cross-sectional cohort studies including individuals of European ancestry in the UK Biobank.

The study reported that monogenic and high polygenic risk were each associated with a more than 2.5-fold increased odds of developing glaucoma and an equivalent mean age at glaucoma diagnosis, with high polygenic risk more than 15-times more common in the general population.

The saliva-based test will change the current one-size-fits-all approach to one of a more personalized approach where high-risk patients are managed with specialist input, while those at a low- and intermediate-risk level can be managed safely and less frequently in optometric primary care.

REFERENCE:

Siggs OM, Han X, Qassim A, Souzeau E, Kuruvilla S, Marshall HN, Mullany S, Mackey DA, Hewitt AW, Gharahkhani P, MacGregor S, Craig JE. Association of Monogenic and Polygenic Risk With the Prevalence of Open-Angle Glaucoma. JAMA Ophthalmol. 2021 Sep 1;139(9):1023-1028. doi: 10.1001/jamaophthalmol.2021.2440.