Intraocular Pressure Fluctuation Research Articles

Assessing the value of the water drinking test in glaucoma-a systematic review and meta-analysis.

This systematic review and meta-analysis examines the relationship between intraocular pressure (IOP) parameters derived from the water drinking test (WDT) and diurnal IOP monitoring, and evaluates the reproducibility of the WDT and its association with future glaucomatous visual field (VF) loss. A literature search was performed on PubMed, EMBASE, and Cochrane Library from inception to 31 March 2023. Cohort, cross-sectional and observational studies reporting WDT results in glaucoma patients were included. Meta analysis with random-effect model was performed using "metafor" package in R version 3.2.1. 641 studies were identified on initial literature search. 38 studies (2479 subjects) were included in final analysis. Meta-analytic estimates of 5 studies (310 subjects) found strong positive correlation in peak IOP between the WDT and diurnal IOP monitoring (r = 0.92, 95% CI = 0.75, 1.08, p < 0.0001). However, there was only weak positive correlation for IOP fluctuation between both methods (r = 0.26, 95% CI = 0.06,0.47, p < 0.0001). Meta-analytic estimates of 3 studies (189 subjects) suggested a trend of the diurnal peak IOP being lower than that derived from the WDT (MD = -2.37 mmHg, 95% Limit of Agreement (LOA) =-5.58,0.84, p = 0.147). Two studies found that a higher WDT peak IOP was associated with greater future VF progression. Two studies demonstrated good reproducibility in peak IOP measurements for WDTs conducted across different days. In conclusion, there was a strong positive correlation between IOP peak measurements from the WDT and diurnal IOP monitoring in glaucoma patients. The WDT peak IOP demonstrated good reproducibility and may be associated with greater future VF progression.

Intraday repeatability of macular layers measurements in glaucomatous and non-glaucomatous patients using spectral-domain optical coherence tomography.

To assess the intraday repeatability of macular architecture measurements in glaucomatous and non-glaucomatous patients using spectral-domain optical coherence tomography (SD-OCT) and to evaluate the independence from intraindividual intraocular pressure (IOP) fluctuations. In this single-center, time-point comparison study, 88 eyes with glaucoma, 53 eyes with ocular hypertension (OHT), and 253 healthy eyes underwent two standardized SD-OCT and intraocular pressure (IOP) measurements on the same day with a 5-h time gap. Bland-Altman plots, intraclass correlation coefficients (ICC), and random-effects model were used to analyze repeatability of entire retinal thickness, retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, and inner nuclear layer measurements. Intraday measurements were highly reproducible in all 3 groups. ICC were greater than 0.90, respectively. The pairwise comparisons of morphometric parameters showed a statistically significant difference (P < 0.001, respectively) between groups (glaucoma vs. control, glaucoma vs. OHT) and a significant influence of time points. No correlation was found between IOP fluctuations and morphometric parameters (P > 0.05, respectively), except for a weak positive correlation with GCL (rho = 0.109, P = 0.031). The evaluation of macular morphometric parameters of SD-OCT showed a high intraday repeatability and an excellent degree of agreement in glaucoma, ocular hypertension, and healthy groups. The fixed effects of time points were statistically significant. Except for a weak positive correlation of ganglion cell layer, variability did not appear to be affected by intraday IOP changes. Additional research is required to fully understand the impact of IOP fluctuations on macular morphometric parameters, considering the small observed IOP changes.

SURGICAL DEMONSTRATION OF PRESSURE DIFFERENTIAL THROUGH AN OPTIC DISK PIT.

To demonstrate intraoperative dynamic flow through an optic disk pit. Retrospective interventional case report. Surgical management of an optic disk pit involved standard, 25-gauge, pars plana vitrectomy, induction of posterior hyaloid separation with triamcinolone stain, temporal peripapillary laser, and SF 6 gas. Intraoperatively, a remnant of stained vitreous at the optic disk head prolapsed into the optic disk pit with higher intraocular pressure but was drawn back into the vitreous cavity as the intraocular pressure was lowered. This clearly demonstrated a pressure differential across the pit. Communication between the vitreous cavity and the perineural space of the optic nerve is described histologically. Our case demonstrated dynamic flow through the optic disk pit with intraoperative fluctuation of intraocular pressure.

Thicker Inner Nuclear Layer as a Predictor of Glaucoma Progression and the Impact of Intraocular Pressure Fluctuation.

Background: Thickening of the inner nuclear layer (INL) or microcystic macular changes has been reported to be implicated in glaucoma patients, but their potential impact on disease progression remains unclear. We investigated the relationship between baseline microcystic macular edema in the INL or INL thickness and subsequent visual field (VF) progression in glaucoma patients. Methods: This retrospective observational study included primary open-angle glaucoma with follow-up exceeding 3 years. We identified macular cystic changes through Spectralis optical coherence tomography and measured the INL thickness using automated segmentation. Glaucoma progression was determined using the Guided Progression Analysis program of the Humphrey filed analyzer, calculating the mean deviation (MD) changes (dB/year). Results: Microcystic macular changes were observed in 12 (7.5%) of 162 patients. Patients with microcystic macular change had thicker INL thickness than those without it (p = 0.010). Progressors had a higher probability of having microcystic macular changes and a thicker average INL thickness than nonprogressors (p = 0.003, p = 0.019). Thicker INL thickness was associated with faster VF progression based on MD slope (dB/year) in the multivariate regression analysis (p = 0.045). Additionally, greater intraocular pressure (IOP) fluctuation was found to be associated with both a thicker INL and the presence of microcystic changes in the multivariate regression analysis (p = 0.003, 0.028). Conclusions: Increased macular INL thickness indicative of INL changes was linked to subsequent VF progression in glaucoma patients. These findings suggest that retinal inner nuclear change could serve as an indicator of progressive glaucoma.

Association of Long-Term Intraocular Pressure Variability and Rate of Ganglion Complex Thinning in Patients With Glaucoma

To evaluate the association of mean intraocular pressure (IOP) and IOP variability (IOP fluctuation [SD of IOP] and the IOP range) with the rate of ganglion cell complex (GCC) layer thinning over time in patients with glaucoma. Prospective cohort study. Participants with at least 4 visits and 2 years of follow-up of optical coherence tomography tests were included. A linear mixed-effect model was used to investigate the association of IOP parameters with the rates of GCC thinning. Subgroup analyses were conducted for eyes with early (MD ≥ -6 dB), and moderate to advanced stage (MD < -6 dB) at baseline. The cohort consisted of 369 eyes of 249 glaucoma patients (282 early glaucoma and 87 moderate to advanced glaucoma) with mean (standard deviation [SD]) age of 68.2 (10.7) years over 5.1 years of follow-up. The mean rate of GCC change was -0.59 (95% confidence interval [CI], -0.67 to -0.52) µm per year. In multivariable models, faster annual rate of GCC thinning was associated with a higher IOP fluctuation (-0.17 [95% CI, -0.23 to -0.11] µm per 1-mmHg higher, P < .001) or higher IOP range (-0.07 [95% CI, -0.09 to -0.05] µm per 1-mmHg higher, P < .001) after adjustment for mean IOP and other confounding factors. Similar results were found for early and moderate to advanced stages of glaucoma. IOP variability showed an independent association with macular change in patients with glaucoma regardless of severity at baseline, even after adjustment for mean IOP, supporting its potential value as a therapeutic target for clinical decision-making.

Design and development of a noninvasive ocular pressure estimator.

A snapshot intraocular pressure (IOP) is ineffective in identifying the IOP peak and fluctuation, especially during sleep. Because IOP variability plays a significant role in the progression of glaucoma, monitoring the IOP, especially during sleep, is essential to capture the dynamic nature of IOP. We aimed to design an ocular pressure estimator (OPE) that can reliably and accurately measure the IOP noninvasively over closed-eyelid condition. Ocular pressure estimator works on the principle that the external pressure applied by raising the IOP of the eyeball is transmitted through a compressible septum to the pressure sensor, thus recording the IOP. A fluid-filled pouch with a pressure sensor was placed over a rubber glove mimicking the eyelid (septum), covering the cornea of enucleated goat eyeballs. A pressure-controlled setup was connected to a goat cadaver eye, which was validated by a rebound tonometer. Cannulation of eyeballs through the lower limbus had the least difference from the control setup values documented using rebound tonometer, compared with cannulation through the optic nerve. Intraocular pressures ranging from 3 to 30 mmHg was induced, and the outputs recorded using OPE were amplified and recorded for 10 minutes (n = 10 eyes). We stratified the randomization of the number of times and the induced pressures. The measurements recorded were found to be linear when measured against an IOP range of 3 to 30 mmHg. The device has excellent reliability (intraclass correlation coefficient, 0.998). The repeatability coefficient and coefficient of variations were 4.24 (3.60 to 4.87) and 8.61% (7.33 to 9.90), respectively. The overall mean difference ± SD between induced IOP and the OPE was 0.22 ± 3.50 (95% confidence interval, -0.35 to 0.79) mmHg across all IOP ranges. Ocular pressure estimator offers a promising approach for reliably and accurately measuring IOP and its fluctuation noninvasively under a condition mimicking a closed eye.

The Effect of Esophagogastroduodenoscopy on Intraocular Pressure.

Esophagogastroduodenoscopy (EGD) is an endoscopic examination of the upper gastrointestinal tract that requires insufflation with gas, leading to intra-abdominal hypertension (IAH). There is evidence suggesting that IAH positively correlates with intracranial pressure (ICP) and possibly with intraocular pressure (IOP). The aim of this study was to examine the effect of a routine screening EGD on the IOP. In this observational study, 25 patients were recruited; 15 males with a mean age of 50 ± 18 years and 10 females with a mean age of 45 ± 14 years. EGD was conducted under sedation in 21 subjects. Both eyes' IOP measurements were performed using Tonopen Avia in the sitting and left lateral decubitus positions before sedation and the start of EGD, and subsequently in the left lateral decubitus position when the endoscope reached the duodenum (D2) and at the end of the procedure. The final measurement was performed in the sitting position 10 min after the end of the procedure. The mean IOP in the sitting position was 15.16 ± 2.27 mmHg, and in the left lateral decubitus position, 15.68 ± 2.82 mmHg. When the gastroscope entered the D2, it was 21.84 ± 6.55 mmHg, at the end of the procedure, 15.80 ± 3.25 mmHg, and 10 min later, 13.12 ± 3.63 mmHg. There was a statistically significant IOP increase when the gastroscope entered the duodenum (p < 0.01). At the end of the gastroscopy, the IOP significantly decreased compared to the one registered when the gastroscope entered the D2 (p < 0.001) and it became similar to the values measured before the EGD, in the same left lateral decubitus position (p > 0.05). Significant changes in IOP were observed during the EGD. IOP fluctuations during EGD should be taken into account, especially in patients that need repeated EGDs during their life or in patients with glaucoma. Further studies are needed to better understand the short-effect and long-effect influence of an IOP increase in these patients.

Long-Term Intraocular Pressure Fluctuation and Epiretinal Membrane in Patients with Glaucoma or Glaucoma Suspect.

Background: A relationship between glaucoma and epiretinal membrane (ERM) has been suggested previously. We investigated the association between intraocular pressure (IOP) fluctuation and idiopathic ERM in patients with glaucoma or glaucoma suspect. Methods: Among patients with glaucoma or glaucoma suspect, data from 43 patients with ERM and 41 patients without ERM were reviewed and analyzed in this retrospective study. The long-term fluctuation of IOP was defined based on the standard deviation of IOP across all visits. Results: Patients with ERM were older and had a higher SD of IOP and a higher proportion of having a history of cataract surgery and greater macular thickness (p = 0.018, 0.049, 0.013, and <0.001, respectively). In multiple logistic regression analysis, the high-IOP-fluctuation group was associated with the presence of ERM (p = 0.047). Among patients with ERM, eyes with stage-3 or -4 ERM had worse visual field defects based on mean deviation than those with stage-1 or -2 ERM (p = 0.025). Conclusions: Long-term IOP fluctuation was associated with idiopathic ERM in patients with glaucoma or glaucoma suspect. Idiopathic ERM could serve as a biomarker for long-term IOP fluctuation in glaucoma patients, particularly in clinics where measuring long-term IOP fluctuation during the first visit is not feasible due to its time-consuming nature.

Continuous 24-hour intraocular pressure monitoring in normal Chinese adults using a novel contact lens sensor system

AimsTo investigate the physiological nyctohemeral intraocular pressure (IOP) rhythms of normal Chinese adults using a novel contact lens sensor system (CLS) that can output IOP in millimetres of mercury (mm...

Relationship between intraocular pressure fluctuation and visual field progression rates in the United Kingdom Glaucoma Treatment Study

To investigate whether intraocular pressure (IOP) fluctuation is independently associated with the rate of visual field (VF) progression in the United Kingdom Glaucoma Treatment Study. Randomized, double-masked, placebo-controlled multicenter trial. Participants with ≥5 VFs (213 placebo, 217 treatment). Associations between IOP metrics and the VF progression rates (mean deviation (MD) and five fastest locations) were assessed with linear mixed models. Fluctuation variables were mean ocular pulse amplitude (OPA), standard deviation (SD) of diurnal IOP (diurnal fluctuation), and SD of IOP at all visits (long-term fluctuation). Fluctuation values were normalized for mean IOP to make them independent from mean IOP. Correlated non-fluctuation IOP metrics (baseline, peak, mean, supine and peak phasing IOP) were combined with principal component analysis (PCA), and principal component 1 (PC1) was included as a covariate. Interactions between covariates and time from baseline modelled the effect of the variables on VF rates. IOP was measured with Goldmann applanation tonometry and OPA with Pascal tonometry. Analyses were conducted separately in the two treatment arms. Associations between IOP fluctuation metrics and rates of MD and five fastest test locations. In the placebo arm, only PC1 was significantly associated with the MD rate (estimate [standard error (SE)]: -0.19 [0.04] dB/year, p<0.001), while normalized IOP fluctuation metrics were not. No variable was significantly associated with MD rates in the treatment arm. For the fastest five locations in the placebo group, PC1 (estimate [SE]: -0.58 [0.16] dB/year, p<0.001), CCT (estimate [standard error (SE)]: 0.26 [0.10] dB/year for 10 μm thicker, p=0.01) and normalized OPA (estimate [SE]: -3.50 [1.04] dB/year, p=0.001) were associated with rates of progression; normalized diurnal and long-term IOP fluctuations were not. In the treatment group, only PC1 (estimate [SE]: -0.27 [0.12] dB/year, p=0.028) was associated with the rates of progression. There is no evidence to support that either diurnal or long-term IOP fluctuation, as measured in clinical practice, are independent factors for glaucoma progression; other aspects of IOP, including mean IOP and peak IOP, may be more informative. OPA may be an independent factor for faster glaucoma progression.

Оценка клинической эффективности нового способа адаптивного управления инфузией при факоэмульсификации

Reduction of the adverse effects of intraoperative intraocular pressure fluctuation referred to as post-occlusion surge on the intraocular structures is an important task for ensuring phacoemulsification safety. In this regard, the method to control infusion during phacoemulsification based on controlling the infusion and aspiration flow rates in combination with monitoring of vacuum parameters was developed. The study was aimed to provide comparative assessment of clinical and functional characteristics of the eye in patients after phacoemulsification using the new and already existing adaptive infusion control methods. A total of 38 patients aged 66.4 ± 7.8 years (15 males and 23 females) in the index group (Optimed Profi system with the use of new method) and 35 patients aged 68.7 ± 7.5 years (16 males and 19 females) in the control group (Centurion Vision System with Active Fluidics) underwent surgery due to cataract. The patients underwent comprehensive eye examination before surgery and on days 1, 7, 30, months 3, 6 after surgery. The smaller loss of corneal endothelial cells on months 3 and 6 after surgery was observed in patients of the index group with grade III and IV cataract (p &lt; 0.05). Comparison of macular microcirculation parameters revealed the reduced FAZ area by month 6 of postoperative follow-up in the index group, along with the increased total vascular density of the deep vasculature (p &lt; 0.001). A significant decrease in the total density of the superficial and deep vascular plexuses by month 6 of postoperative follow-up was observed in the control group (p &lt; 0.05). The use of new adaptive infusion control method contributes to effective phacoemulsification of cataracts of varying density with the lower percentage of the corneal endothelial cells lost in the late postoperative period.

Intraocular pressure fluctuations assessment in professional wind instrument players.

Due to the long-time that wind musicians spend playing their instruments, it is important to investigate if intraocular pressure could be affected by this activity. To assess the intraocular pressure fluctuations and fluctuations affecting factors in professional wind musicians while playing different tones. Thirty professional wind musicians (23.0 ± 3.20 years) were recruited from the Professional Music College of A Coruña. A questionnaire about environmental/demographic factors was given to participants. Intraocular pressure was measured four times by ICare IC100 tonometer: before, during low and high-pitched tones, and immediately after stopping playing the wind instrument. Pairwise comparison revealed statistical differences between measurement points (Sidak, all p ≤ 0.019), except between before playing and while playing low-pitched tones (Sidak, p = 1.000). Intraocular pressure increases during high pitch playing and decreases after stopping playing. No significant differences in intraocular pressure fluctuation were reported between physically active (>2 days/week) and non-physically active participants (Unpaired t-test, p = 0.680). All intraocular pressure values were positively correlated (Pearson's correlation, all r ≥ 0.505, p ≤ 0.004). Intraocular pressure fluctuations were negatively correlated with musical playing years (Pearson's correlation, r = - 0.396, p = 0.030). There were no significant correlations among intraocular pressure fluctuation and gender, age, weight, height, or daily time playing (Pearson's correlation, all p ≥ 0.058). Professional wind musicians suffer intraocular pressure peaks while playing high-pitched tones; therefore, ocular fundus evaluation and visual campimetry should be performed as routine tests in the visual exam of this population.

Comparison of intraocular pressure fluctuation and glaucoma progression rate between phakic and pseudophakic eyes in pseudoexfoliation glaucoma

The management of patients with concurrent pseudoexfoliation glaucoma (PXG) and cataract is challenging given its worse prognosis compared to other glaucoma types and the increased risk associated with cataract surgery. In this retrospective study, we investigated the long-term outcomes of cataract surgery in patients with PXG. We enrolled patients with PXG who had undergone cataract surgery at least 2 years previously and compared them with mean deviation (MD) matched patients with phakic eyes. The results showed that both groups experienced a decrease in MD, with the group of pseudophakic eyes exhibiting a significantly higher rate of decline (−2.15 ± 2.66 dB/year vs. −0.86 ± 0.95 dB/year; P = 0.040). Similarly, there was a trend towards more rapid thinning of the retinal nerve fiber layer in the pseudophakic group (−2.92 ± 2.34 μm/year vs. −1.79 ± 1.71 μm/year; P = 0.074). No significant differences in the intraocular pressure parameters were observed between the two groups. Multivariate analysis revealed that pseudophakic lens status was significantly associated with a faster rate of MD decline in patients with PXG (regression coefficient, −1.391; P = 0.022). These findings underscore the importance of close monitoring of patients with pseudophakic PXG to effectively manage glaucoma progression.

Short‐term intraocular pressure fluctuation in primary angle closure glaucoma

Purpose: To identify the most sensitive period for detecting significant circadian and ultra‐short‐term intraocular pressure (IOP) fluctuation associated with disease progression in primary angle closure glaucoma (PACG).Methods: PACG eyes, which had been followed up for over 2 years under the CUHK PACG Longitudinal (CUPAL) Study, were recruited. Eyes with or without functional or structural glaucomatous progression were classified into ‘progressive’ or ‘stable’ groups based on serial visual field (VF) and retinal nerve fibre layer (RNFL) thickness documentations, respectively. Circadian and ultra‐short‐term IOP fluctuations were recorded by Sensimed Triggerfish® sensors with 288 readings over 30 s, at 5‐min intervals, over a 24‐h period. The circadian IOP fluctuation was represented by smoothed sensor output signals using B‐spline smoothing transform and described by functional data analysis. In each of seven activity‐related 1‐h periods during the examining day, the mean value of the amplitude‐frequency profiles of the signal fluctuations in twelve 30‐s intervals, which represent the ultra‐short‐term IOP fluctuation, was calculated by semi‐variogram/semi‐variance. The signals were compared between ‘progressive’ and ‘stable’ groups by permutation tests on functional t‐statistics.Results: Among the 25 recruited PACG eyes, 16 eyes were classified as RNFL ‘progressive’ group (the mean rate of change in global RNFL thickness: −0.199 ± 0.128 μm/month). Statistically significant differences were found during the time periods from 22:00 to 23:00 and from 07: 00 to 08:00 in gradients that reflected by the first derivative of the IOP fluctuation curve, as well as from 23:00 to 24:00 and 08:00 to 09:00 in curvatures that reflected by the second derivative of the IOP fluctuation curve, between the VF progressive and the VF stable groups (p &lt; 0.05). Gradients differences were also found during the time periods from 24:00 to 01:00 and 02:00 to 03:00 between structural progressive and stable groups (p &lt; 0.05). Higher signal fluctuations, in terms of amplitude‐frequency, were found during the first 1‐h period of sleeping in the RNFL ‘progressive’ group, compared to the RNFL ‘stable’ group (p = 0.028).Conclusions: Between RNFL ‘progressive’ and ‘stable’ PACG eyes, significant differences in circadian IOP fluctuation and ultra‐short‐term IOP fluctuation at the 1‐h period after falling asleep were identified. Large circadian IOP fluctuations may be associated with disease progression in PACG eyes. The first hour of sleeping may be the most sensitive period for detecting significant short‐term IOP fluctuation in PACG eyes.

Long term intraocular pressure fluctuation and epiretinal membrane in patients with glaucoma or glaucoma suspect

Aims/Purpose: The associations between ERM and glaucoma were suggested in several studies. In an animal model undergoing intermittent IOP elevations, a reactive gliosis, a phenotype of ERM, was found in the optic nerve head. We investigated the association between intraocular pressure (IOP) fluctuation and idiopathic ERM in patients with glaucoma or glaucoma suspect.Methods: In this retrospective study, a total of 84 patients with glaucoma or glaucoma suspect were included. Among them, forty one patients had no ERM and forty three patients had ERM. Long‐term fluctuation of IOP was defined as the standard deviation (SD) of IOP at all visits. Patients were divided into two groups according to the median value of SD of IOP: the low IOP fluctuation group and high IOP fluctuation group. Among patients with available heart rate variability (HRV) data, the relationship between the HRV parameter and IOP fluctuation was analysed.Results: Patients with ERM was older and had higher IOP fluctuation and higher proportion of having history of cataract surgery and greater macular thickness (p = 0.018, 0.049, 0.013, &lt; 0.001). The high IOP fluctuation group showed higher proportion of patients with ERM (62.5%) than the low IOP fluctuation group (36.4%, p = 0.028). In the multiple logistic analysis, higher IOP fluctuation group were associated with the presence of ERM (p = 0.047). Among patients with ERM, eyes with stage 3 or 4 ERM had worse visual field defects based on mean deviation than those with stage 1 or 2 ERM (p = 0.025). The high IOP fluctuation group showed higher level of low frequency HRV, an index of sympathetic cardiac control than the low IOP fluctuation group (p = 0.027). Intereye comparison in eyes with ERM and the fellow eyes without ERM, eyes with ERM (2.2 ± 0.9 mmHg) had higher fluctuation of IOP than those without ERM (2.0 ± 0.8 mmHg, p = 0.029).Conclusions: In conclusion, long‐term IOP fluctuation had the relevance to idiopathic ERM in patients with glaucoma or glaucoma suspect. In glaucoma patients with ERM, more advanced stage ERMs were associated with worse visual field damage. Further studies are needed to determine if long‐term IOP fluctuation affects the progression of glaucoma and ERM.

Correlation of diurnal fluctuations in intraocular pressure and progression of chronic simple glaucoma

Purpose: To study the correlation between diurnal fluctuations of intraocular pressure and progression of chronic simple glaucoma. Introduction: Out of all the risk factors for glaucoma, only modifiable risk factor is intraocular pressure. A lot of studies have been done to determine the relationship between the behavior of diurnal intraocular pressure (IOP) and progression of glaucoma. The results varied and are inconclusive because the visual field damage could have occurred at a time when the IOP was high, although it was low at the time of measurement. Materials and Methods: A prospective study was conducted on all patients diagnosed or suspected CSG with office IOP &lt;25 mmHg. Measurement of diurnal fluctuation in IOP was done by taking 2 hourly IOP readings after admitting patients in hospital for 1 day. Results: The mean baseline diurnal fluctuation of our patients was 8.5 mmHg with values reaching as high as 13.6 mmHg in some patients. 28.8% of the patients of our study group showed progression at the end of 2-year follow-up. As the baseline diurnal fluctuation increased, the number of patients showing progression increased.

Exfoliation syndrome and exfoliation glaucoma ‐ Current research and Management in Georgia

Exfoliation Syndrome (XFS) is an age‐related disorder of extracellular matrix affecting millions of people worldwide. It is the most common identifiable cause of glaucoma which is characterized by much more severe clinical course, more fluctuation of intraocular pressure (IOP), less response to medical treatment, faster progression of optic nerve atrophy and visual field deterioration, more frequent need of surgical treatment.XFS is a heritable condition. This fact is long known from familial aggregation studies. Very little is known about the mechanisms of disease development. This is especially true about Exfoliation Glaucoma (XFG), considering that not every XFS patient converts to XFG.The only evidence‐based treatment of XFG nowadays is IOP lowering, although addressing mechanisms of IOP elevation could be the best preventive and treatment measure.The aim of this talk is to summarize the current status of genetic studies of XFS/XFG and to provide some tips for treatment based on several clinical examples.

Retinal neurodegeneration in intraocular pressure fluctuation rat model

Aims/Purpose: The role of IOP fluctuation is controversial in development and progression of glaucoma in clinical trials. We investigated effects of intraocular pressure fluctuation on retinal neurodegeneration and their mechanisms in rats.Methods: Male Sprague–Dawley rats were treated with IOP‐lowering eyedrops (brinzolamide and latanoprost) or saline for 8 weeks. IOP‐lowering eyedrops were put on Monday and Thursday for the irregular instillation group or daily for the regular instillation group, and saline was put daily for the control group. IOP was measured daily under general anaesthesia using a rebound tonometer. Oxidative stress, reaction of microgliosis and the number of retinal ganglion cells (RGCs) were measured.Results: Mean IOP was lower both in the irregular instillation group (9.6 ± 0.4 mmHg) and the regular instillation group (9.5 ± 0.4) than the control group (10.1 ± 0.4 mmHg, p &lt; 0.001). Standard deviation (SD) of IOP was higher in the irregular instillation group (0.8 ± 0.1 mmHg) than the regular instillation group (0.5 ± 0.1 mmHg) or the control group (0.6 ± 0.3 mmHg, p &lt; 0.001). Oxidative stress measured by dihydroethidium, oxidative DNA damage exhibited by 8‐hydroxy‐2′‐deoxyguanosine, and immunostaining for nitrotyrosine were upregulated (All p &lt; 0.001). Expression of glial fibrillary acidic protein in the optic nerve head was more increased in irregular instillation group than the control group, but not in the regular instillation of eyedrops (p = 0.001). Expression of anti‐ionized calcium binding adaptor molecule (Iba‐1), a marker for microglia and P2Y12 known as a chemotactic receptor for microglia did not show a significant difference between the irregular instillation group and the control group. Expression of cleaved caspase‐3 was greater in the irregular instillation group than other two groups (p &lt; 0.001). The number of RGCs stained with anti‐Brn3a antibody was lower in the irregular instillation group than other two groups (p = 0.002).Conclusions: IOP fluctuation induced by treatment of irregular instillation of IOP‐lowering eyedrops reduced the number of RGCs. Our findings indicate that IOP fluctuation induced by treatment of irregular instillation of IOP‐lowering eyedrops could lead to degeneration of RGCs probably by increasing oxidative stress and microgliosis.

Safety and efficacy profile of intravitreal ranibizumab vs dexamethasone in treatment of naïve diabetic macular edema.

To compare the safety and efficacy parameters of intravitreal ranibizumab vs intravitreal dexamethasone (IVD) in the treatment of patients with naïve diabetic macular edema (DME) in terms of best-corrected visual acuity (BCVA), central macular thickness (CMT), and possible complications like intraocular pressure (IOP) rise and cataract progression. A hospital-based prospective and comparative study of naïve DME patients was conducted between November 2020 and October 2021 with a minimum follow-up (F/U) period of 6 months. Thirty phakic patients received one dose of IVD implant (Group A) and the other 30 (Group B) received three consecutive monthly doses of ranibizumab. The main exclusion criteria were steroid responders and the presence of ocular inflammation. The mean pre-injection CMT in Group A was 405µ and reduced to 297.07µ at 3 months and 278.35µ at 6 months. Mean increase in logMAR BCVA was 0.55. The mean pre-injection IOP was 16.28 and 17.64 mm of Hg at 6 months. In Group B, the mean pre-injection CMT was 401.07µ and reduced to 276.1µ at 3 months and 292.9µ at 6 months. Mean BCVA increased to 0.37. The mean pre-injection IOP was 17.28 mm Hg and 16.42 mm Hg at 6 months. There was no significant progression of cataract in both groups. The mean decrease in CMT was comparable in both the groups at 6 months F/U with an improvement of BCVA with no significant IOP fluctuation or cataract progression. Hence, IVD appears to be noninferior to ranibizumab in the treatment of naïve DME.

A first-in-human pilot study of a novel electrically-passive metamaterial-inspired resonator-based ocular sensor embedded contact lens monitoring intraocular pressure fluctuations

Glaucoma is a leading cause of blindness with no cure, but early treatment and effective monitoring can often slow the progression of the disease. Monitoring of glaucoma is based on the measurement of intra-ocular pressure (IOP) that is a physiological parameter related to the mechanical state and parameters of the eye. Conventionally, diagnosing and assessing the progression of glaucoma is based on the method of measuring IOP discretely at clinics. Recent studies have demonstrated the importance of continuously monitoring IOP for 24 h to elucidate the effect of circadian rhythm. In this work, a metamaterial-inspired electrically-passive sensor-embedded contact lens is presented to monitor the IOP fluctuations based on a first-in-human pilot study. The sensor inside the contact lens is an electrically passive, metamaterial-based resonator that can be measured using a wearable antenna patch. The system has been tested with six healthy volunteers during an experiment to induce deliberate IOP changes via water-loading and placing the individuals in supine position using a recliner seat. The initial data compared with tonometer measurements suggest that the system can be used to assess the variation of IOP continuously.