Intraocular Pressure Profiles Research Articles

Comparison of intraocular pressure profiles during the water drinking test and the modified diurnal tension curve

ObjectivesTo compare intraocular pressure (IOP) during the water drinking test (WDT) and modified diurnal tension curve (mDTC) in open-angle glaucoma (OAG) patients, using multimodal, observer-masked tonometry.MethodsOpen-angle glaucoma subjects were prospectively enroled, excluding those who had undergone glaucoma filtration or laser surgery. Two-hourly mDTC Goldmann applanation (GAT) and rebound tonometry (RT) was performed between 8:00 and 16:00, and every 15 min for 45 min after ingestion of 800mls of water. Blood pressure, heart rate, pupillometry measurements, and optical coherence tomography (AS-OCT) were also recorded.ResultsForty-two subjects’ right eyes were included. 48% were using topical glaucoma medication. Mean baseline IOP was 14.9 ± 4.52 mmHg, with mean visual field mean deviation (±SD) −5.05 ± 5.45 dB. Strong association was found between maximum IOP during mDTC and WDT (r = 0.90, 95% CI 0.82–0.95 p < 0.0001) with agreement (mDTC-WDT) bias −0.82 mmHg, 95% LoA −1.46 to −0.18. During the WDT, mean systolic blood pressure (±SD) increased from 140.0 ± 20.0 to 153.3 ± 24.0 mmHg (p < 0.0001), mean heart rate ( ± SD) reduced from 69.5 ± 11.3 bpm to 63.6 ± 10.0 bpm (p < 0.0001), and temporal iridocorneal angle increased from 29.2 ± 6.0° to 29.6 ± 5.2° (p = 0.04).ConclusionThis study presents repeated, observer-masked IOP data showing strong correlation between maximum IOP during mDTC and WDT using multimodal tonometry. This supports WDT as a meaningful alternative to mDTC when investigating diurnal IOP characteristics in clinic, with reduced time requirements and associated costs.

Effect of the iridocorneal angle size on the diurnal pressure profile in a glaucoma suspect cohort and patients with glaucoma

PurposeTo evaluate the impact of the iridocorneal angle size (ICAS) on the diurnal intraocular pressure (IOP) in patients with suspected glaucoma (SG).MethodPatients with any eye-pressure lowering medication or previous ocular surgery were excluded. In a retrospective study set, diurnal IOP profiles of 120 patients (205 eyes) within a 48-h period were analysed by regression analysis. Of those eyes, 44 were diagnosed to have glaucoma. The remaining eyes were used as healthy control group (HCG).ResultsThe overall mean IOP was 15.63 mmHg ± 2.72 mmHg and mean ICAS was 23.92° ± 4.74°. In the glaucoma cohort, mean IOP was 18.77 ± 1.86 mmHg and mean ICAS was 25.02° ± 4.96°. In the HCG, mean IOP was 14.77 ± 2.25 mmHg and mean ICAS was 23.62° ± 4.64°. In the total cohort, as well as in the subgroups (HCG or glaucoma), regression analysis showed no significant impact even of the minimum ICAS, which was larger than 10°, on average (P = 0.89), maximum (P = 0.88), and range of IOP (P = 0.49) within 48 h. The difference between glaucoma cohort and HCG cohort was significant in terms of IOP (P < 0.001), but not for minimum ICAS (P = 0.07). Chi-square test showed no increase in prevalence of IOP peaks of > 21 mmHg within 48 h in eyes with an angle between 10° and 20° (P = 0.18).ConclusionAn ICAS of larger than 10° in HCG or glaucoma patients with an open-angle does not influence the minimum, average, maximum or range of IOP. Additionally, an angle size larger than 10° does not allow the prediction of IOP changes in these two cohorts.

Comparison between Intraocular Pressure Profiles over 24 and 48 h in the Management of Glaucoma.

(1) Background: Due to significant variation, sporadic IOP measurements often fail to correctly assess the IOP situation in glaucoma patients. Thus, diurnal-nocturnal IOP profiles can be used as a diagnostic tool. The purpose of this study is to determine the additional diagnostic value of prolonged IOP profiles. (2) Methods: All diagnostic 48 h IOP profiles from a large university hospital, between 2017 and 2019, were reviewed. Elevated IOP > 21 mmHg, IOP variation > 6 mmHg and nocturnal IOP peaks were defined as IOP events of interest and counted. The analysis was repeated for the first 24 h of every IOP profile only. The Chi2 test was used for statistical analysis. (3) Results: 661 IOP profiles were included. Specifically, 59% of the 48 h IOP profiles revealed IOP values above 21 mmHg, and 87% showed IOP fluctuation greater than 6 mmHg. Nocturnal peaks in the supine position could be observed in 51% of the patients. In the profiles censored for the first 24 h, the fractions were 50%, 71% and 48%, (p < 0.01, p < 0.01 and p = 0.12) respectively. (4) Conclusions: the 48 h IOP profiles identified more patients with IOP events of interest than the 24 h IOP profiles. The additional diagnostic value must be weighed against the higher costs.

Deep sclerectomy-trabeculectomy with mitomycin C in treating glaucoma: postoperative long-term results.

To determine the long-term postoperative outcomes of deep sclerectomy-trabeculectomy (DST) with mitomycin C (MMC) in the treatment of glaucoma. Patients who underwent DST with MMC between 2010 and 2017 were included in this retrospective observational study. Complete success was defined as postoperative intraocular pressure (IOP) ≤21 mm Hg or 30% reduction of IOP from baseline without any topical IOP-lowering agent, and qualified success defined as IOP≤21 mm Hg or 30% reduction of IOP from baseline with/without single topical agent. We evaluated the surgical success rates and complication rates of this procedure, as well as described the IOP profiles, best corrected visual acuity (BCVA) profiles and mean deviations (MD) of Humphrey visual field (HVF) 24-2 performance at each follow-up time point. Mixed linear regression models were constructed to determine estimated predictive values of demographic data, use of topical IOP-lowering agents, baseline and postoperative IOP and optical profiles (e.g., BCVA and MD). Totally 98 eyes (mean postoperative follow-up 67.5mo) showed mean IOP reduction at every follow-up interval. Both median BCVA and MD of visual fields were maintained throughout the follow-up intervals when comparing to baseline. The number of IOP-lowering medications decreased from 2.8±0.8 to 0.3±0.7 (P=0.068). Totally 84 (85.7%) eyes achieved complete success at final follow-up. Transient hyphaema and transient choroidal effusion developed in 15 eyes (15.3%) and 11 eyes (11.2%) respectively. Other complications included shallow anterior chamber in 5 eyes (5.1%), bleb leak in 4 eyes (4.1%), bleb revision in 7 eyes (7.1%), bleb needling in 9 eyes (9.2%) and repeat trabeculectomy in 1 eye (1.0%). There was no endophthalmitis, blebitis or macular oedema. There was no significant correlation between postoperative IOP control and postoperative BCVA. DST with MMC demonstrates effective and sustained long-term outcomes in the treatment of glaucoma with no major complication.

Innovative approaches to measuring intraocular pressure

AbstractAlthough different factors have been implicated in the development and progression of glaucoma, intraocular pressure (IOP) remains the main modifiable risk factor. Goldmann applanation tonometer (GAT) considers the “gold standard” for measuring IOP. The main deficiency of GAT, however, is the static nature of its measurements and that it is dependent on corneal biomechanics, central corneal thickness as well as scleral stiffness. The single measurement of IOP for the management of glaucoma provides limited information since it does not take into account the natural fluctuation of IOP, individual ranges, IOP peaks or variations throughout the day. Although the role of IOP fluctuations in glaucoma progression is not clearly defined, there is consensus on the importance of understanding the circadian profiles of IOP in glaucoma patients. Given the limitations of GAT for the actual measurement of IOP, different tonometers have been designed with the aim of advancing in self‐tonometry as Icare HOME, or obtaining independent measurements of corneal biomechanics, as Ocular Response Analyser (ORA), Pascal dynamic contour tonometer or the Corvis ST tonometer. Research to monitor IOP is based on three different strategies: (1) self‐tonometry; (2) permanent monitoring of the IOP; and (3) the temporary monitoring of the IOP. Currently, the sensors in contact lenses allow the IOP profiles to be recorded semi‐continuously for 24 hours with a minimally invasive technique, independent of the patient's position and the activity performed, opening new perspectives in the knowledge and management of glaucoma.

Telemetric non-contact intraocular pressure monitoring with an implanted sensor in patients with glaucoma: long-term safety report and monitoring data

Background/aimsGlaucoma is a chronic disease that requires lifelong monitoring and treatment. However, its control is limited due to discontinuous intraocular pressure (IOP) monitoring related to the practitioners’ office hours. Implantable...

VSN16S, an agonist of the cannabinoid receptor, reduces IOP profiles and exhibits neuroprotective properties in a rat model of glaucoma

AbstractPurposeThere is an unmet need for new drugs in glaucoma that can effectively prevent glaucoma progression. We assessed the effects of VSN16S and AG‐020, the agonists of the cannabinoid receptor, on intraocular pressure (IOP) and neuroprotection using a rat model of ocular hypertension (OHT).Methods20 male Dark Agouti (DA) rats aged 8–10 weeks were randomly located into 4 groups (n = 5): OHT‐only, OHT+vehicle, OHT+VSN16S, and OHT+AG‐020. All animals had IOP surgically elevated in the left eye (OS) by injection of hypertonic saline into the episcleral veins. Except for OHT‐only, animals in the other 3 groups have received eye drops in OS either vehicle or VSN16S or AG‐0202 at 10 mg/ml, twice daily for 3 weeks following OHT‐induction. IOPs were recorded in both eyes at baseline (BL), day1, week1, 2, and 3 using a Tonopen. Animals were in vivo imaged for retinal ganglion cell (RGC) apoptosis in both eyes using DARC (Detection of Apoptotic Retinal Cells) at BL and week3 before culled. Retinal whole‐mounts were immunostained with a Brn‐3a antibody to assess RGC survival. DARC spots and RGC counts were assessed by blinded algorithm analysis.ResultsSurgical procedure induced a significant increase in IOP profiles in all animal groups compared to the contralateral eye (OD), and peak levels occurred at day1 (p &lt; 0.001). In the OHT eyes treated with VSN16S, IOPs at week1 exhibited a sharp reduction (p &lt; 0.05), and integrate IOP at week3 was significantly lower than vehicle controls (p &lt; 0.01). However, AG020 showed no effect on IOP. IOP elevation resulted in a significant increase in DARC counts (RGC apoptosis) in all groups, compared to the baseline. DARC counts revealed a significant reduction in the OHT eyes treated by VSN16S, compared to the OHT‐only and vehicle groups (p &lt; 0.01), but less of a reduction of DARC counts was observed with AG‐020 treatment (p &lt; 0.05). A significant reduction of Brn‐3a+RGC density was seen in the OHT‐only group compared to naïve controls (p &lt; 0.05), and VSN16S treatment demolished the difference although no significance was found on Brn‐3a+RGC density between VSN16S and controls.ConclusionsVSN16S exerted neuroprotective properties in OHT‐induced RGC loss, which may be associated with lowering IOP profiles. DARC is a useful tool in the assessment of drug efficacy in retinal neurodegenerative diseases.

Low-noise compliance-design for intraocular pressure contact lens sensor

Continuous intraocular pressure profiles from chipless contact lens sensor (CLS) reduces misdiagnosis and improves treatment monitoring. Tests showed IOP profiles from ex vivo porcine eye trials have low noise. The in vivo profiles are confounded by noise from tears and eyelids. The addition of reference elements successfully reduced a part of the noise, but mechanical noise is still ignored. Hybrid mechanical design strategy to reduce noise is examined in this study. The dual-compliance, dual-element CLS is designed, prototyped, and tested. Results showed that the noise is reduced to less than± 3 mmHg in different environments. Analysis showed the design reduced deformation signal overlap, increased the signal separation, and boosted the sensitivity. The dual-compliance, high-sensitivity CLS design reduces CLS IOP sensing noise effectively.

Deployment of the Water Drinking Test and iCare HOME Phasing for Intraocular Pressure Profiling in Glaucoma Evaluation.

Intraocular pressure (IOP) profiling is an important component of the glaucoma examination. Two techniques for profiling are the water drinking test (WDT) and iCare HOME phasing, but the correlations between techniques and their ease of deployment have not been studied. These questions are important in determining suitability for clinical deployment. This study aimed to compare the IOP results of the WDT and iCare HOME phasing in patients with suspected or newly diagnosed glaucoma. Ninety-eight consecutive patients attending a glaucoma clinic underwent IOP profiling using both techniques. For the WDT, patients ingested 10 mL/kg body weight of water after a baseline applanation IOP measurement and then underwent serial IOP measurements approximately every 15 minutes, ceasing after 30 minutes of consecutive measurements within 3 mmHg of baseline. Patients successfully certified for self-administration of the iCare HOME were loaned the instrument for 1 week and instructed to take four measurements per day. Twenty-seven patients (28%) successfully obtained four measurements per day using iCare HOME, and 96 patients (98%) were able to complete the WDT. Intraocular pressure profiles showed no difference between the time for peak IOP and across nearly all IOP parameters obtained from profiling except for the standard deviation of IOP measurements obtained using the iCare HOME (P = .005). There were moderate correlations between peak IOPs obtained using each technique (r = 0.67, P = .001, right eye; r = 0.66, P = .002, left eye) but no correlation between the daily range (iCare HOME) or peak-trough difference (WDT; r = 0.21, P = .28, right eye; r = 0.27, P = .02, left eye). Bland-Altman analysis returned similar results for peak and range. Intraocular pressure profiling using both techniques can reveal the peak IOP, and these measurements are strongly correlated. Most patients were unable to complete the iCare HOME according to the manufacturer's recommendations. Clinicians should select the most appropriate technique for each patient.

Combined ab-interno trabeculectomy and cataract surgery induces comparable intraocular pressure reduction in supine and sitting positions.

To analyze the therapeutic effect of combined ab-interno trabeculectomy and cataract surgery on intraocular pressure (IOP) levels in supine and sitting postures during a 24-hour IOP profile. Twenty-six eyes of twenty-six patients receiving ab-interno trabeculectomy using electroablation of the trabecular meshwork combined with cataract surgery or stand-alone were included in this retrospective analysis. IOP change during 24-hour IOP profiles within two years postoperatively were analyzed for eyes receiving surgery ("study eyes") and compared to fellow eyes, which had not received surgery. Clinical data including mean sitting IOP (siIOP), mean supine IOP (suIOP) and the number of topical antiglaucomatous medications (TAM) were extracted from patients' files. Preoperatively, siIOP was 17.6±5.3 mm Hg in study and 17.1±4.7 mm Hg in fellow eyes (P=0.347). Patients were treated with an average of 2.8±1.0 TAM. Best corrected visual acuity (BCVA) was significantly worse in study eyes (P<0.001), visual field function was marginally not significantly different (P=0.057). After surgery 9.6±6.8mo, study eyes had a mean siIOP of 14.5±3.6 mm Hg (IOP reduction: -3.2 mm Hg, P=0.009), a mean suIOP of 18.0±3.5 mm Hg, and an average of 1.3±1.34 TAM (P<0.001), while in fellow eyes, mean siIOP was 16.2±3.4 mm Hg and mean suIOP was 20.5±5.1 mm Hg. Postoperatively, the relative IOP increase between sitting and supine postures was approximately 30% in both study and fellow eyes (P=0.99). IOP after ab-interno trabeculectomy shows a comparable relative reduction in both supine and sitting position. Classical trabeculectomy is known to lower suIOP overproportionally.

Short- and long-term agreement and reproducibility of 48-hours intraocular pressure measurements in glaucoma patients

BackgroundGlaucomatous eyes often show strong intraocular pressure (IOP) fluctuations and individual measurements at different time points are necessary for personalized therapy. To survey IOP variations 48-hours diurnal and nocturnal IOP measurements were performed on two consecutive days. Aims of this study were to investigate the short-term repeatability of 48-hours measurements within one patient’s IOP profile and long-term repeatability between two separate IOP profiles of the same patient.MethodsA retrospective cohort study was performed evaluating data of 90 glaucoma patients in a German university medical center between 2006 and 2013. All patients underwent two separate diurnal IOP profiles of 48 h. IOP was measured at 8 am, 2 pm, 6 pm, 9 pm using Goldmann applanation tonometry and at 12 midnight using Perkins tonometry in supine position on two consecutive days. Intraclass correlation coefficients (ICC) were calculated to evaluate agreement for the same time points (each time point agreement) and for consecutive measurements within the IOP profiles (between time point agreement). ICC ≤ 0.4 was defined as poor agreement, 0.4–0.75 as moderate and ≥ 0.75 as excellent. Differences between time points were investigated by Bland Altman plots.ResultsEach time point measurements of profile 1 showed moderate to excellent agreement (ICCs 0.62–0.93). There was a moderate to excellent agreement for measurements between time points of profile 1 (ICCs day one 0.57–0.86, day two 0.71–0.90). Profile 2 was performed at a median interval of 12.0 months (quartiles 11.0 to 21.0). Each time point agreements within profile 2 showed ICCs from 0.23 to 0.81. It showed moderate to excellent agreement for changes between time points (ICCs 0.53–0.94). Day two demonstrated ICCs from 0.74 to 0.88. Long term IOP repeatability (over both pressure profiles) showed moderate to good agreement (ICCs 0.39–0.67).ConclusionsShort and long-term agreement of IOP measurements evaluated by diurnal IOP profiles is moderate to good. Due to mostly moderate agreements, which we believe represent IOP fluctuations, we conclude that it is necessary to perform 48-hours IOP profiles to gain a better overview of the individual IOP fluctuations.

Recent progress of continuous intraocular pressure monitoring

AbstractGlaucoma, a chronic optic neuropathy, is the leading cause of irreversible blindness in the world. Elevated intraocular pressure (IOP) has been considered to be the major contributor to glaucoma for a long time and is currently proved to be the only modifiable risk factor for the progression of optic neuropathy. IOP fluctuates throughout the day with a circadian rhythm change and is affected by body gesture changes. Moreover, the IOP spike usually occurs at night or in the early morning. Therefore, the current clinical practice of single and static measurements of IOP during office hours is not conducive to the early diagnosis and treatment of glaucoma. This review focuses on current advances in implantable and noninvasive IOP sensors for obtaining 24‐hour continuous IOP profiles. The content summarizes and classifies IOP sensors based on their working principles and provides representative examples of the sensors for IOP monitoring. Finally, the review further analyzes the challenges of current IOP sensors for clinical practice and puts forward the prospect of IOP sensors in the future.

Wearable dual-element intraocular pressure contact lens sensor

Continuous profiles of intraocular pressure (IOP) can improve the diagnostic accuracy and the management of glaucoma. Profiles from contact lens sensors (CLS) have significant errors. The IOP error from a single resonator sensor is large in a variable ocular environment. A dual-resonator sensor is developed in this study to reduce the error. Contact lens sensors were prototyped and tested on rubber eyes. A new IOP-signal gauged model for dual-resonator sensor developed in this study successfully removed the environmental noise. The IOP error was reduced to less than ±3 mmHg. This study showed that the new dual-resonator sensor and the IOP model reduced IOP errors to levels comparable to the errors in ex-vivo and in-vivo tonometry. The new dual-resonator sensor can provide IOP profiles to improve the diagnostic accuracy and management of glaucoma.

The impact of intraocular pressure fluctuations and other factors on conversion of ocular hypertension to primary open-angle glaucoma.

To evaluate the role of intraocular pressure (IOP) fluctuations and other factors on conversion of ocular hypertension to open-angle glaucoma (OAG) within a retrospective, longitudinal cohort study. The study population included patients with ocular hypertension defined by IOP > 21mmHg with normal appearing optic discs and no visual field defect. IOP fluctuation, mean and maximum were examined in 61 eyes over a follow-up period of 36months (standard deviation (SD) 24). All patients underwent at least two 48-h IOP profiles including night-time IOP measurements in the supine position, visual field examinations, Heidelberg retina tomograph analyses (HRT) and optic disc photographs. Regression analyses were performed to demonstrate the impact of IOP parameters, myopia, sex, cup/disc ratio and visual field results on conversion to glaucoma. While IOP fluctuation and mean did not impact conversion, myopia proved to be a risk factor (HR 14.4; 95% CI: [3.9-53.0]; p ≤ 0.001). Over an average of three years, 6/61 converted to OAG. The study yielded a mean long-term IOP over all available pressure profiles of 18.1mmHg (SD 3.2) and an IOP fluctuation of 1.9mmHg (SD 1.1) within a mostly treated cohort. Conversion-free five-year rate was 59.8%. The amount of fluctuation we measured in our study sample did not result in the development of glaucoma in treated ocular hypertension patients. Myopic subjects with ocular hypertension are at a higher risk for glaucoma conversion than non-myopic ocular hypertensive subjects are.

Role of 24-Hour Intraocular Pressure Monitoring in Glaucoma Management.

Glaucoma is the leading cause of irreversible blindness worldwide and the prevalence is on the rising trend. Intraocular pressure (IOP) reduction is the mainstay of treatment. The current practice of IOP monitoring is based on spot measurements during clinic visits during office hours. However, there are up to 50% of glaucoma patients who had normal initial IOP, while some treated patients continued to have progressive glaucomatous optic nerve damage even with a low IOP. Recent studies have shown that the IOP of glaucoma patients fluctuated during the day with different patterns, and some of them had peak IOP outside office hours. These findings provided us with new insights on the role of 24-hour IOP monitoring in managing normal tension glaucoma and patients with progressive deterioration despite apparently well-controlled IOP. Nevertheless, results to date are rather inconsistent, and there is no consensus yet. In this review, we briefly highlighted the current modalities of 24-hour IOP monitoring and summarized the characteristic 24-hour IOP pattern and the clinical relevance of IOP parameters in predicting glaucomatous progression in different glaucoma subtypes. We also discussed the therapeutic efficacy of current glaucoma treatment modalities with respect to the mentioned 24-hour IOP profiles, so as to strengthen the role of 24-hour IOP monitoring in identifying and stratifying the risks of progression in glaucoma patients, as well as optimizing treatments according to their IOP profiles.

Fabry-Pérot optical sensor and portable detector for monitoring high-resolution ocular hemodynamics.

Our understanding of ocular hemodynamics and its role in ophthalmic disease progression remains unclear due to the shortcomings of precise and on-demand biomedical sensing technologies. Here, we report high-resolution in vivo assessment of ocular hemodynamics using a Fabry-Pérot cavity-based micro-optical sensor and a portable optical detector. The designed optical system is capable of measuring both static intraocular pressure and dynamic ocular pulsation profiles in parallel. Through a dynamic intensity variation analysis method which improves sensing resolution by 3-4 folds, our system is able to extract systolic/diastolic phases from a single ocular pulsation profile. Using a portable detector, we performed in vivo studies on rabbits and verified that ophthalmic parameters obtained from our optical system closely match with traditional techniques such as tonometry, electrocardiography, and photo-plethysmography.

Inter-relationship between ocular perfusion pressure, blood pressure, intraocular pressure profiles and primary open-angle glaucoma: the Singapore Epidemiology of Eye Diseases study

ObjectiveTo elucidate the inter-relationship between ocular perfusion pressure (OPP), blood pressure (BP), intraocular pressure (IOP) profiles and primary open-angle glaucoma (POAG) in a multiethnic Asian population.MethodsParticipants were recruited from the...

Sustained Delivery of Timolol Maleate for Over 90 Days by Subconjunctival Injection.

Medical treatment of glaucoma relies on intraocular pressure (IOP)-lowering medications, typically administered daily by the patient. While these medications are effective when applied correctly, patient adherence is a major obstacle in glaucoma treatment. We have developed a sustained-release formulation of timolol maleate that can be injected subconjunctivally to avoid patient noncompliance. A biodegradable microsphere formulation for timolol maleate was injected subconjunctivally in normal rabbits. We measured timolol levels in tears, aqueous humor, vitreous humor, and serum of study rabbits. Furthermore, IOP profiles were recorded longitudinally. Tissue compatibility and side effects were evaluated using histochemistry. The microsphere formulation led to measureable amounts of timolol in the aqueous humor and the tear film for up to 90 days. Timolol was not detectable in the serum at any time. A significant reduction of IOP was observed in treated eyes. Clinically, the subconjunctival administration of the microspheres was well tolerated with no signs of inflammation or infection. The absence of local inflammation was confirmed by histology. A single subconjunctival administration of timolol microspheres achieved delivery and IOP reduction in rabbits for up to 90 days without local or systemic inflammation or toxicity. This approach has the potential to improve the management of glaucoma in patient populations, who are challenged to adhere to a regimen of daily eye drops.

Optic nerve head and intraocular pressure in the guinea pig eye

The guinea pig is becoming an increasingly popular model for studying human myopia, which carries an increased risk of glaucoma. As a step towards understanding this association, this study sought to characterize the normal, developmental intraocular pressure (IOP) profiles, as well as the anatomy of the optic nerve head (ONH) and adjacent sclera of young guinea pigs. IOP was tracked in pigmented guinea pigs up to 3 months of age. One guinea pig was imaged in vivo with OCT and one with a fundus camera. The eyes of pigmented and albino guinea pigs (ages 2 months) were enucleated and sections from the posterior segment, including the ONH and surrounding sclera, processed for histological analyses - either hematoxylin and eosin (H&E) staining of paraffin embedded, sectioned tissue (n = 1), or cryostat sectioned tissue, processed for immunohistochemistry (n = 3), using primary antibodies against collagen types I–V, elastin, fibronectin and glial fibrillary acidic protein (GFAP). Transmission and scanning electron microscopy (TEM, SEM) studies of ONHs were also undertaken (n = 2 & 5 respectively). Mean IOPs ranged from 17.33 to 22.7 mmHg, increasing slightly across the age range studied, and the IOPs of individual animals also exhibited diurnal variations, peaking in the early morning (mean of 25.8, mmHg, ∼9 am), and decreasing across the day. H&E-stained sections showed retinal ganglion cell axons organized into fascicles in the prelaminar and laminar region of the ONHs, with immunostained sections revealing collagen types I, III, IV and V, as well as elastin, GFAP and fibronectin in the ONHs. SEM revealed a well-defined lamina cribrosa (LC), with radially-oriented collagen beams. TEM revealed collagen fibrils surrounding non-myelinated nerve fiber bundles in the LC region, with myelination and decreased collagen posterior to the LC. The adjacent sclera comprised mainly crimped collagen fibers in a crisscross arrangement. Both the sclera and LC were qualitatively similar in structure in pigmented and albino guinea pigs. The well-organized, collagen-based LC of the guinea pig ONH is similar to that described for tree shrews and more similar to the human LC than that of other rodents that lack collagen. Based on these latter structural similarities the guinea pig would seem a promising model for investigating the relationship between myopia and glaucoma.

Effects of recurring intraocular pressure elevations on the retina and the autoimmune component

PurposeIn glaucoma, complex changes of IgG serum autoantibody (Aab) repertoire highlight the possible contribution of an autoimmune component in the pathogenesis of this neurodegenerative disease. An elevated intraocular pressure (IOP) and its fluctuations are considered as major risk factors. The aim of the study was to identify the systemic influence of fluctuations using recurring pressure peaks and drops in a glaucoma animal model.MethodsSedated male Long Evans rats experienced a unilateral, intermittent IOP manipulation using a silicone loop adjusted around the eye globe for 1 hour during 27 treatments. The pressure profile included pressure peaks to 35 and 45 mmHg and drops to a physiologic value of 8 mmHg. Contralateral (n = 12) and untreated eyes (n = 14) served as controls. Neurodegeneration was determined after paraphenylenediamine staining and Brn3a staining. Microglia activation was identified after Iba1 staining in retinal cross‐sections. Changes of serum immunoreactivities were identified using a microarray approach with a glaucoma‐specific antigen Setup.ResultsA loss of axon density (as axons/0.05 mm2) of treated eyes (19624 ± 1709) compared to contralateral (21943 ± 1510; p &lt; 0.01) and untreated eyes (22267 ± 1408; p &lt; 0.01) occured, which was confirmed by retinal ganglion cell count. Next to an activation of microglia, upregulated Aab reactivities for GST, transferrin, and NSE were identified in serum of treated animals in comparison to control serum.ConclusionsThis animal model including pressure peaks and drops allows the establishment of individual IOP profiles. The retina and the optic nerve sustained a significant damage and an altered autoimmune repertoire could be induced. A significant influence of recurring pressure fluctuations could be demonstrated using this sophisticated glaucoma animal model.