REICHERT TONO-VERA TONOMETER

 

The Reichert^® Tono-Vera^® Tonometer features a patented ActiView™ Positioning System, providing a guided view to obtain precise intra-ocular pressure (IOP) measurements.

The positioning system guides the operator to the apex of the cornea. Using gentle rebound tonometer technology and eliminating the need for topical anesthetic, Tono-Vera automatically measures the IOP when aligned. 

The Tono-Vera^® ActiView™ Positioning System features a full color view of the eye combined with intuitive, interactive alignment prompts to guide the user precisely to the apex of the cornea. When proper alignment is achieved Tono-Vera automatically measures the IOP, providing a result in as few as three measurements. Intuitive color-coded rings indicate the reliability of the reading.

The machine can be used with no routine calibration required.

Tono-Vera is available in two models: Rechargeable or AA Battery. The Rechargeable and AA Battery Packs are interchangeable.

The included multi-purpose Tono-Vera Base has the docking part for the Tono-Vera and charger for the rechargeable model. The base is also used for storing the Ocu-Dot^® Tonometer Probes.

The machine has an innovative FlexiSoft™ Forehead Rest for easy distance control and patient comfort.

Tono-Vera is Bluetooth enabled, allowing for software updates and Electronic Health Record connectivity.

Ocu-Dot^® Tonometer Probes:

Ocu-Dot^® Tonometer Probes are specially designed for use with Tono-Vera® Tonometers. Each comes in an individual plastic vial to allow for easy loading and disposal. The probes come as 100 pieces per boxes.

WEBSITE LINK: https://www.reichert.com/en/products/tono-vera

OCTA: Non-perfused areas for diagnosis

 

Optical Coherence Tomography Angiography (OCTA) can display blood vessels by visualizing signal changes caused by moving particles, in this case erythrocytes in the blood. It is able to visualize areas of reduced capillary perfusion which occur in various diseases, including glaucoma.

Studies have usually quantified the decreased perfusion by using vessel density (VD), which is the percentage of vessel pixels in the image. However, this method may miss subtle changes which occur early during the course of the disease. Newer methods quantify the non-perfused or inter-capillary areas between the vessels. This depends on accuracy of vessel segmentation, which can be a limiting factor for reliability in certain cases.

Intercapillary areas computed from perfusion-distance measures are less sensitive to errors in the vessel segmentation since the distance to the next vessel is only slightly changed if gaps are present in the segmentation. Therefore, inter-capillary areas computed from perfusion-distance measures are less sensitive to errors.

Schottenhamml and colleagues have recently reported a new method based on features computed from the probability density function of these perfusion-distance areas. [1]

Deep learning methods (Artificial Intelligence, AI) can detect areas of reduced capillary perfusion. Therefore, these regions can act as a very good biomarker for detecting glaucoma. Unfortunately, vessel density, the commonly used parameter, is not sensitive enough to detect small changes occurring in these areas. Therefore, the authors utilized the non-perfusion or inter-capillary areas to quantify the areas between the vessels. This approach is probably more sensitive since even if only a few vessels are not visible on OCTA and VD is not much affected, the region of non-perfused areas can change appreciably.

In order to quantify the inter-capillary areas, a very accurate segmentation of the vascular network is needed, since small errors and gaps in the segmentation will affect the results significantly. The authors have found that a more robust alternative to using inter-capillary areas is to use perfusion distance. This approach computes the distance from any pixel to its next vessel pixel and is consequently not as sensitive to small errors in vessel segmentation.

REFERENCE:

[1] Schottenhamml J, Würfl T, Ploner S, Husvogt L, Lämmer R, Hohberger B, Maier A, Mardin C. Glaucoma detection using non-perfused areas in OCTA. Sci Rep. 2024 May 5;14(1):10306. doi: 10.1038/s41598-024-60839-4. PMID: 38705883; PMCID: PMC11070420.

ULTRA-PROCESSED FOOD INTAKE AND RISK OF GLAUCOMA

 

Ultra-processed foods (UPF) have become extremely popular, especially among the younger generation, and the unhealthy effects of these foods are being reported extensively.

UPF has been defined as a type of food that is made up of industrial formulations primarily consisting of food-derived substances, additives, and other artificial ingredients. These foods are designed to be convenient, long-lasting, and very tasty, but often contain high levels of salt, sugar, and fat, while providing little nutritional value, such as snacks, sweetened beverages, frozen meals, or fast food.

The Seguimiento Universidad de Navarra (SUN) Project is an ongoing study to look into the association of UPFs with a higher risk of glaucoma. The prospective study is being performed on Spanish university graduates since 1999.

As of September 2019, 22,899 individuals had joined the SUN Project. However, individuals already diagnosed with glaucoma and those who met other exclusion criteria were excluded from the analysis. Finally, 19,225 participants have been included in the study.

Dietary intake was measured at the beginning of the study using a 136-item semiquantitative food-frequency questionnaire (FFQ).

After adjusting for several covariates, participants with the highest UPF consumption (more than four servings of UPF per day) were at higher risk of glaucoma (hazard ratio (HR) = 1.83; 95% confidence interval (CI) 1.06 to 3.17) when compared to participants in the lowest category of UPF consumption (one serving per day).

Subgroup analyses showed a significant multiplicative interaction with age (p = 0.004) and omega 3:6 ratio (p = 0.040).

However, an association between UPF consumption and glaucoma was only found in older participants (aged ≥ 55 years), in men, in the most physically active group, in the group of non- or former smokers, in those with a lower omega 3:6 ratio, and in those with a lower energy intake.

Regarding the contribution of each type of UPF group, UPF coming from sweets showed a significant risky effect (HR = 1.51; CI 95% 1.07 to 2.12).

MECHANISM OF GLAUCOMA:

High UPF consumption leads to increased blood glucose levels, which along with oxidative stress and limited cell division in ocular tissues, leads to formation of advanced glycation end products. UPF itself is a major source of advanced glycation end products. This causes damage to ocular tissues.

UPF consumption is likely related to the resting metabolic rate, which is mediated through variations in the production of high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), and interleukin-1beta (IL-1β). UPF consumption has also been linked to an increase in interleukin-6 (IL-6) levels, which has been linked to the survival and degeneration of retinal ganglion cells and the development of glaucoma.

Artificial sweeteners, thickeners, emulsifiers, and preservatives may have indirect and direct effects on immune cells, contributing to metabolic dysregulation. Increased consumption of these types of foods, may increase inflammation levels, which, in turn, could increase the risk of glaucoma.

REFERENCE:

López-Gil, J.F.; FernandezMontero, A.; Bes-Rastrollo, M.; Moreno-Galarraga, L.; Kales, S.N.; Martínez-González, M.Á.; MorenoMontañés, J. Is Ultra-Processed Food Intake Associated with a Higher Risk of Glaucoma? A Prospective Cohort Study including 19,255 Participants from the SUN Project. Nutrients 2024, 16, 1053. https://doi.org/10.3390/ nu16071053

GLOBAL EXTENT OF UNDETECTED GLAUCOMA

 

GUEST AUTHOR

DR. GHUNCHA KHATOON

DEPT OF COMMUNITY MEDICINE, AJMAL KHAN TIBBIYA COLLEGE, 

AMU, ALIGARH, INDIA

Undetected glaucoma is a challenging public health problem as it increases the risk of visual impairment, even in those cases where early detection could be beneficial. The loss of vision in a large population can affect the quality-of-life and socio-economic condition of the community.

The levels of undetected glaucoma globally are not clear. Reported prevalence ranges between 33% and 98%. However, a meta-analysis has shown that nearly half of all glaucoma cases are undetected world-wide. And, this number is expected to increase in the future.

Understanding these levels can spur the development of effective public health strategies and policy-level changes (e.g., screening programs) to prevent avoidable blindness.

The meta-analysis reviewed 61 articles from 55 population-based studies (n ¼ 189 359 participants; n ¼ 6949 manifest glaucoma). [1]

Variation in Undetected Glaucoma by Geographical Region:

For manifest glaucoma, the highest proportion of previously undetected cases was observed in Africa and the least in Oceania. Africa (odds ratio [OR], 12.70; 95% confidence interval [CI], 4.91e32.86) and Asia (OR, 3.41; 95% CI, 1.63e7.16) had significantly higher odds of undetected manifest glaucoma as compared with Europe.

For POAG, the highest proportion of previously undetected cases was observed in Africa and the least in North America. Africa (OR, 8.84; 95% CI, 2.64e29.62) and Asia (OR, 4.66; 95% CI, 2.07e10.51) showed significantly higher odds of undetected POAG as compared with Europe, whereas the differences between other geographical regions and Europe were statistically insignificant.

Variation in Undetected Glaucoma by Human Development Index (HDI):

Countries with low HDI had undetected cases in the proportion of 94.56% (95% CI, 92.13e96.27), compared to 70% in countries with medium to very high HDI. Countries with medium HDI (OR, 0.20;95% CI, 0.10e0.42), high HDI (OR, 0.20; 95% CI, 0.09e0.47), and very high HDI (OR, 0.12; 95% CI, 0.06e0.24) showed significantly lower odds of undetected manifest glaucoma as compared with countries of low HDI.

Variation in Undetected Glaucoma by Ethnicity:

Africans (OR, 5.55; 95% CI, 2.41e12.78) and Asians (OR, 2.62; 95% CI, 1.26e5.48) showed significantly higher odds of undetected manifest glaucoma as compared with people of European ancestry.

Projected Number of Undetected Primary Open-Angle Glaucoma Cases:

Asia alone accounts for 58.4% of all undetected POAG cases worldwide because of its sheer population size.

The number of undetected POAG cases is projected to increase by 53.2% to affect 67.06 million (95% CI, 64.11e69.59 million) people by 2040.

The largest increase will be seen in Africa (86.3%), whereas the highest number of undetected POAG cases in 2040 will remain in Asia.

Variation in Undetected Glaucoma by Asia Sub-region:

In Asia, South Asia (OR, 2.19; 95% CI, 1.01e4.77) showed significant higher odds of undetected manifest glaucoma cases as compared with East Asia, whereas the differences between the other sub-regions and East Asia were insignificant.

Variation in Undetected Glaucoma by Other Factors:

The odds of undetected POAG were lower in urban habitations (OR, 0.52; 95% CI, 0.27e0.99) as compared with rural habitation globally.

Reasons for undetected glaucoma not only include socio-economic factors and better medical facilities, but also from a complex interplay between multiple factors that include individual, community, and policy-level short-comings.

In a study performed in USA in 2014, approximately 2.4 million persons had undetected and untreated glaucoma. Overall, prevalence of both diagnosed and undiagnosed glaucoma was much higher in minorities (African-Americans and Hispanics) and the elderly. [2]

REFERENCES:

1. Soh Z, Yu M, Betzler BK, Majithia S, Thakur S, Tham YC, Wong TY, Aung T, Friedman DS, Cheng CY. The Global Extent of Undetected Glaucoma in Adults: A Systematic Review and Meta-analysis. Ophthalmology. 2021 Oct;128(10):1393-1404. doi: 10.1016/j.ophtha.2021.04.009. Epub 2021 Apr 16. PMID: 33865875.
2. Shaikh Y, Yu F, Coleman AL. Burden of undetected and untreated glaucoma in the United States. Am J Ophthalmol. 2014 Dec;158(6):1121-1129.e1. doi: 10.1016/j.ajo.2014.08.023. Epub 2014 Aug 22. PMID: 25152501.

 

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. 

ALSO SEE THIS: https://ourgsc.blogspot.com/search?q=helicobacter

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.

See post on AMTT here: https://ourgsc.blogspot.com/search?q=AHMAD%27S

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.