Azithromycin and Sildenafil May Have Protective Effects on Retinal Ganglion Cells via Different Pathways: Study in a Rodent Microbead Model.

Decreased blood flow to the optic nerve (ON) and neuroinflammation are suggested to play an important role in the pathophysiology of glaucoma. This study investigated the potential neuroprotective effect of azithromycin, an anti-inflammatory macrolide, and sildenafil, a selective phosphodiesterase-5 inhibitor, on retinal ganglion cell survival in a glaucoma model, which was induced by microbead injection into the right anterior chamber of 50 wild-type (WT) and 30 transgenic toll-like receptor 4 knockout (TLR4KO) mice. Treatment groups included intraperitoneal azithromycin 0.1 mL (1 mg/0.1 mL), intravitreal sildenafil 3 µL, or intraperitoneal sildenafil 0.1 mL (0.24 µg/3 µL). Left eyes served as controls. Microbead injection increased intraocular pressure (IOP), which peaked on day 7 in all groups and on day 14 in azithromycin-treated mice. Furthermore, the retinas and ON of microbead-injected eyes showed a trend of increased expression of inflammatory- and apoptosis-related genes, mainly in WT and to a lesser extent in TLR4KO mice. Azithromycin reduced the BAX/BCL2 ratio, TGFß, and TNFα levels in the ON and CD45 expression in WT retina. Sildenafil activated TNFα-mediated pathways. Both azithromycin and sildenafil exerted a neuroprotective effect in WT and TLR4KO mice with microbead-induced glaucoma, albeit via different pathways, without affecting IOP. The relatively low apoptotic effect observed in microbead-injected TLR4KO mice suggests a role of inflammation in glaucomatous damage.

Histological and molecular characterization of glaucoma model induced by one or two injections of microbeads to the anterior chamber of mice.

PURPOSE: To characterize glaucoma-induced damage following injections of plastic microbeads into the anterior chamber of mice. METHODS: Mice were divided into three groups: a single plastic microbeads injection (n = 21); two consecutive plastic microbead injections to the right eye at 1-week intervals, 4 of which with two consecutive saline injections in the left eye (n = 15); and an additional control group of two consecutive saline injections at 1-week intervals (n = 6). Intraocular pressure (IOP) was measured weekly. Retinal thickness, ganglion cells (RGCs) and axonal loss, inflammatory and gliosis reactions were measured at week four. Molecular analysis using qRT-PCR in the microbeads injection groups focused on expression levels of inflammation and glaucoma-related genes. RESULTS: Mean IOP following single injection at 4 weeks was significantly elevated compared to baseline in injected eyes (14.5 ± 3.3 mmHg vs. 11.1 ± 2.5 mmHg, respectively, p = 0.003) and not in fellow eyes (13.2 ± 2.9 mmHg vs. 12.2 ± 2.9, respectively, NS). Six (35.3%) bead-injected eyes had IOP ≥ 17 mmHg compared with 2 (11.8%) saline-injected control eyes. Retinal thickness in injected and fellow eyes was 193.7 ± 15.5 µm and 223.9 ± 15.5 µm, respectively (p = 0.03). RGC loss in injected and fellow eyes was 16.0 ± 0.5 and 17.6 ± 0.7 cells per 200 µm, respectively (p = 0.005). Retinal gliosis, axonal loss and inflammatory cell infiltration to the bead-injected eyes were noted. Molecular analysis following double injection showed STAT3 expression decreased in the glaucoma-induced optic nerves (0.69 ± 0.3 vs. 1.16 ± 0.3, p = 0.04), but increased in the glaucoma-induced retinae (p = 0.05) versus saline; retinal IL-1ß decreased significantly (0.04 ± 0.04 vs. 0.36 ± 0.2, p = 0.02). TNF-α, NFkB and SOD-1 expression did not change. CONCLUSION: One/two injections of microbeads elevated IOP, with measurable neuronal damage. An inflammatory response was detected in the injured retina and optic nerve. The therapeutic significance of these findings should be explored.

Ocular surface temperature differences in glaucoma.

PURPOSE: Accumulating evidence suggests that neuroinflammation and immune response are part of the sequence of pathological events leading to optic nerve damage in glaucoma. Changes in tissue temperature due to inflammation can be measured by thermographic imaging. We investigated the ocular surface temperature (OST) profile of glaucomatous eyes to better understand the pathophysiology of these conditions. METHODS: Subjects diagnosed with glaucoma (primary open angle glaucoma [POAG] or pseudo exfoliation glaucoma [PXFG]) treated at the Sam Rothberg Glaucoma Center (11/2019-11/2020.) were recruited. Healthy subjects with no ocular disease served as controls. The Therm-App thermal imaging camera was used for OST acquisition. Room and body temperatures were recorded, and the mean temperatures of the medial cantus, lateral cantus, and cornea were calculated with image processing software. RESULTS: Thermographic images were obtained from 52 subjects (52 eyes: 25 POAG and 27 PXFG) and 66 controls (66 eyes). Eyes with glaucoma had a significantly higher OST compared to controls (mean 0.9 ± 0.3°C, p < 0.005). The difference between the two groups remained significant after adjustment for age, sex, intraocular pressure (IOP) and room and body temperatures. Lens status and topical IOP-lowering medication did not significantly affect OST. A subgroup analysis revealed that the OST was higher among eyes with POAG compared to eyes with PXFG, but not significantly. CONCLUSIONS: Differences in the OST between glaucomatous and normal eyes strengthens current thinking that inflammation affects the pathophysiology of glaucoma. Longitudinal studies are warranted to establish the prognostic value of thermographic evaluations in these patients.

Ocular Surface Temperature: Characterization in a Large Cohort of Healthy Human Eyes and Correlations to Systemic Cardiovascular Risk Factors.

PURPOSE: To characterize ocular surface temperature (OST) in healthy eyes and its association with systemic risk factors of cardiovascular and ischemic heart disease. METHODS: This prospective cross-sectional study included consenting subjects who were examined at the Institute for Medical Screening in Sheba Medical Center. A Therm-App™ thermal imaging camera (Opgal LTD, Israel) was used for OST acquisition, and the mean OST of the medial canthal, lateral canthal, and central cornea regions were measured. Room and body temperatures were also recorded. Past medical and ocular history as well as data from various clinical examinations performed at the same visit were obtained. RESULTS: Thermographic images were obtained from 186 subjects, 150 of which were included in the final analysis. OST was significantly higher in the medial canthal, central cornea, and lateral canthal regions in people with a history of ischemic heart disease (p = 0.02, p = 0.02, and p = 0.03, respectively). There were no significant OST differences (ANOVA test) associated with the presence of hypertension, diabetes mellitus, or active smoking status. CONCLUSIONS: OST correlated positively with the presence of ischemic heart disease. This correlation, its pathophysiological base, and its clinical application warrants further investigation.

Glaucoma Publication Trends in Leading General Ophthalmology Journals During the Past Quarter Century: Where Are the Clinical Trials?

PRCIS: During the past quarter century, the rate of glaucoma-related publication in general ophthalmology journals increased due to higher representation in "experimentally oriented" journals. The rate of glaucoma randomized controlled clinical trial (RCT) articles decreased during the same time period. PURPOSE: To evaluate trends in rate of glaucoma publications in leading general ophthalmology journals over the past quarter century. MATERIALS AND METHODS: Q1 ophthalmology journals Web sites were reviewed. Only journals not limited to certain subspecialty were considered "general" and included in the analysis. In addition we categorized journals orientation as either "clinical" or "experimental." The PubMed search engine was used to collect publications from the selected journals between January 1, 1995 to December 31, 2019. Publications captured by "glaucoma" or "ocular hypertension" filters were considered glaucoma related. The fraction of glaucoma articles out of total number of articles within each year for each journal was calculated. A linear mixed effects model was applied to detect trends in glaucoma publication rates during the study period. RESULTS: Eight journals were included: 4 "clinically oriented" and 4 "experimentally oriented." The PubMed search yielded 72,750 publications, of which 9329 (12.8%) considered "glaucoma related." Percentage of glaucoma publications remained stable within "clinically oriented" journals, and significantly increased within "experimentally oriented" journals (annual change of 0.3%, P<0.001). The number of glaucoma-related RCTs decreased significantly in each (annual change of -0.21% and -0.13%, respectively, P<0.05). CONCLUSIONS: There has been a significant rise in the rates of glaucoma publications in "experimentally oriented" journals, while their representation in "clinically oriented" journals remained stable over the past quarter century. This change might be due to the increasing efforts to develop more advanced methods for evaluation and treatment in glaucoma, although still unable to address clinical demands. The decrease in glaucoma-related RCT articles might indicate reduced funding for such research.

Er:YAG laser-assisted filtration surgery: initial results in rabbits.

BACKGROUND: Glaucoma is a leading cause of global blindness, especially preventable blindness. The increased prevalence of glaucoma has led to a growing demand for newer, safer, more rapid, and simpler treatments for the reduction of intraocular pressure (IOP). In this study, we evaluated the safety and feasibility of performing filtration glaucoma surgery with an Ab-Interno Er:YAG laser in rabbits. METHODS: Nine New Zealand White rabbits age 16 weeks were studied. After subconjunctival injection of mitomycin C (MMC), a novel Ab-Interno Er:YAG laser probe was inserted into the anterior chamber (AC) through a clear corneal 1 mm paracentesis and directed at the trabecular meshwork adjacent to the MMC injection area. A pulsed laser beam was applied to create a patent sclerostomy connecting the AC to the subconjuctival space, resulting in a filtering bleb. The laser system used was the Er:YAG laser system - LAS25-FCU, (Pantec Biosolutions AG, Liechtenstein). Parameters used: Wave lengh: 2940 nm, Pulse length: 100-400 µsec,frequency: 250 Hz. Average laser power in accordance to the fiber tip diameter: 0.85 W(range 0.8-0.92 W). Complete ocular exams, including IOP measurements, were performed on 1, 7, 14, and 23 days postoperatively. Three rabbits were sacrificed on days 1, 14, and 23, and histological examinations were performed on all nine eyes. RESULTS: All procedures resulted in a functional medium-large superior bleb without significant complications. The bleb was sustained in all rabbits by day 14 and in one of the three rabbits that reached the last follow-up at 23 days. No cases of postoperative hypotony were observed. There was a transient significant reduction in mean IOP on postoperative days 5 and 7 (P = 0.028). Histopathological analysis revealed a patent full-thickness scleral tunnel with only a minor degree of surrounding coagulation necrosis. CONCLUSIONS: The Ab-Interno laser sclerostomy procedure is potentially safe and effective based on initial experience in an in-vivo rabbit animal model.

Surgical outcomes of Ahmed glaucoma valve implantation with plate fixation using vicryl sutures or no plate fixation.

PURPOSE: To summarize the surgical outcomes of Ahmed glaucoma valve (AGV) implantation with plate fixation with vicryl absorbable sutures or no plate suturing. METHODS: This study was a retrospective case series that included all glaucoma patients who underwent AGV implantation surgery with vicryl absorbable sutures for plate fixation or without plate fixation by a single surgeon between 2014 and 2019. We reviewed their medical records and retrieved clinical data on intra- and postoperative complications, best-corrected visual acuity, intraocular pressure (IOP), and number of IOP-lowering medications. RESULTS: Twenty out of 29 eyes (29 patients, mean age 61.04 ± 27.1 years, 17 men) underwent AGV implantation without plate fixation and nine had AGV implantation with fixation with vicryl sutures. Complications were observed in 15 cases (51.7%). Nine of these were defined as failure due to the need for removal or repositioning of the AGV or for further surgery for uncontrolled IOP, of which five were no-fixation cases (5/20, 25%) and four were vicryl-fixation cases (4/9, 44.4%). Six of all surgical failures were related to AGV migration (6/9, 66.6%). There were three cases of extrusion and one case of plate migration in the no-fixation group, and two cases of plate migration and one case of extrusion in the vicryl-fixation group. CONCLUSION: AGV implantation without suture plate fixation or with vicryl suture fixation had a high complication and failure rate, often necessitating reoperation and AGV removal. The high rate of tube-related complications observed after both techniques does not favor either of them. The use of non-absorbable sutures for suturing of the AGV plate is recommended.

Visual Field Endpoints Based on Subgroups of Points May Be Useful in Glaucoma Clinical Trials: A Study With the Humphrey Field Analyzer and Compass Perimeter.

PRECIS: Visual field (VF) endpoints based on average deviation of specific subsets of points rather than all points may offer a more homogeneous data set without necessarily worsening test-retest variability and so may be useful in clinical trials. PURPOSE: The purpose of this study was to characterize the outcome measures encompassing particular subsets of VF points and compare them as obtained with Humphrey [Humphrey visual field analyser (HVF)] and Compass perimeters. METHODS: Thirty patients with imaging-based glaucomatous neuropathy performed a pair of 24-2 tests with each of 2 perimeters. Nonweighted mean deviation (MD) was calculated for the whole field and separate vertical hemifields, and again after censoring of points with low sensitivity (MDc) and subsequently including only "abnormal" points with a total deviation probability of <5% (MDc5%) or <2% (MDc2%). Test-retest variability was assessed using Bland-Altman 95% limits of agreement (95%LoA). RESULTS: For the whole field, using HVF, MD was -7.5±6.9 dB, MDc -3.6±2.8 dB, MDc5% -6.4±1.7 dB, and MDc2% -7.3±1.5 dB. With Compass the MD was -7.5±6.6, MDc -2.9±1.7 dB, MDc5% -6.3±1.5, and MDC2% -7.9±1.6. The respective 95%LoA were 5.5, 5.3, 4.6, and 5.6 with HVF, and 4.8, 3.7, 7.1, and 7.1 with Compass. The respective number of eligible points were 52, 42±12, 20±11, and 15±9 with HVF, and 52, 41.2±12.6, 10±7, and 7±5 with Compass. With both machines, SD and 95%LoA increased in hemifields compared with the total field, but this increase was mitigated after censoring. CONCLUSION: Restricting analysis to particular subsets of points of interest in the VF after censoring points with low sensitivity, as compared with using the familiar total field MD, can provide outcome measures with a broader range of MD, a markedly reduced SD and therefore more homogeneous data set, without necessarily worsening test-retest variability.

Surgical Outcomes of Ahmed Glaucoma Valve Implantation Without Plate Sutures: A 10-Year Retrospective Study.

PRCIS: Ahmed glaucoma valve (AGV) implantation without plate fixation resulted in high rates of complications related to plate or tube movement. PURPOSE: Scleral suturing of the plate of AGV is associated with technical difficulty and potential complications. This study summarizes the surgical outcomes of 10 years of experience with AGV implantation without suture plate fixation. METHODS: The medical records of all glaucoma patients who underwent AGV implantation surgery without plate fixation between 2009 and 2019 at the Sheba Medical Center (Tel Hashomer, Israel) were retrospectively reviewed. Clinical data on intraoperative and postoperative complications, best-corrected visual acuity, intraocular pressure, and number of intraocular pressure-lowering medications were retrieved. RESULTS: Included were 95 eyes of 95 patients (53 men, 42 women; mean age, 54.9±17.5 y). The mean follow-up was 687±673 days. In total, 37 patients (37/95, 38.%) had AGV-related complications, of whom 28 (29.5%) required additional intervention. Women had a significantly higher rate of complications than men (21/42, 50% vs. 16/53, 30.2%, respectively, P=0.049). The 2 most common complications were AGV migration in 13 eyes (13.7%) and tube exposure/AGV extrusion in 9 eyes (9.5%). AGV was removed in 10 cases. CONCLUSIONS: In this cohort, omitting suture AGV plate fixation resulted in high rates of complications related to plate or tube movement, the need for further intervention, and AGV removal. Therefore, we cannot recommend this surgical technique.

Improved sensitivity of microperimetric outcomes for clinical studies in age-related macular degeneration.

To investigate sensitive outcome measures based exclusively on abnormal points in microperimetry testing of eyes with intermediate age-related macular degeneration (iAMD). 25 eyes of 25 subjects with iAMD had undergone 2 successive tests of mesopic microperimetry with the Macular Integrity Assessment Microperimeter (MAIA), using a custom grid of 33 points spanning the central 14 degrees of the macula. Each point was defined as abnormal if its threshold sensitivity was lower than 1.65 standard deviations (SD) (5%) or 2 SD (2.5%) than the expected threshold in healthy eyes according to the MAIA internal database. Among the 25 eyes there were 11.8 ± 9 and 8.4 ± 8.2 abnormal points at < 5% and < 2.5%, with mean deviation of thresholds from normal - 4.9 ± 1.2 dB and - 5.8 ± 1.5 dB, respectively. These deviations were greater, and their SD smaller, compared with the complete microperimetry grid, - 2.3 ± 2.0 dB. The 95% limits of agreement for average threshold between the 2 successive tests were smaller when only abnormal points were included. Analyzing only abnormal grid points yields an outcome parameter with a greater deviation from normal, a more homogenous dataset, and better test-retest variability, compared with analysis of all grid points. This parameter may thus be more sensitive to change, while moderately limiting the number of potential recruits. The proposed outcome measures should be further investigated as potential endpoints in clinical trials in iAMD.

The effect of trabeculectomy and glaucoma drainage device implantation on postural intraocular pressure changes in glaucomatous eyes.

PURPOSE: To investigate the effect of trabeculectomy and glaucoma drainage device implantation on posture related intraocular pressure (IOP) changes in glaucomatous eyes. METHODS: Eyes in this prospective study were divided into three groups: those that underwent Ahmed glaucoma valve implantation (Ahmed group), those that underwent trabeculectomy with mitomycin C (trabeculectomy group) and those treated medically (medication group). IOP was measured in the sitting position, and after 15 min in the left lateral decubitus position using a Tonopen XL, and a Goldmann applanation tonometer (GAT). For GAT measurements in the left lateral decubitus position, we used a specialized system comprised of a motorized bed attached to a modified slit-lamp table. RESULTS: 111 eyes of 64 glaucoma patients were included in the analysis: 19 in the Ahmed group, 46 in the trabeculectomy group and 46 in the medication group. The difference in IOP between the sitting and supine positions was significant in the medication (2.23 mmHg) and trabeculectomy (1.48 mmHg) groups, but not in the Ahmed group (0.53 mmHg). This significance was reached with the GAT, but not with the Tonopen. A rise of 5 mmHg or more between the sitting and supine positions was documented in 5.2%, 4.3% and 15.2% of eyes in the Ahmed, trabeculectomy and medication groups, respectively. Intraclass correlation coefficient for IOP measurements in the supine position demonstrated good correlation between the two tonometers. CONCLUSIONS: Ahmed valve surgery significantly reduces postural IOP response as compared with medically treated controls. There was no significant difference between Ahmed valve and trabeculectomy in terms of their effect on the postural IOP change.

FOXC1 variant in a family with anterior segment dysgenesis and normal-tension glaucoma.

Our study describes the glaucoma phenotype in a family with Axenfeld-Rieger syndrome (ARS) and a FOXC1 variant. Included were 20 subjects from a large three generation family of Jewish Indian ancestry. Subjects underwent a comprehensive ophthalmic examination including automated perimetry and optical coherence tomography. Eight subjects were available for molecular analysis which included whole genome sequencing on selected patients and Sanger sequencing for variant screening. Eleven patients demonstrated a wide spectrum of Axenfeld-Rieger anomaly signs and symptoms. These ranged from subtle angle abnormalities to remarkable anterior segment abnormalities such as corectopia, iris adhesions and strands. Among them, six had glaucoma and two were glaucoma suspects. Of the six subjects with glaucoma three had high-tension glaucoma and two had normal-tension glaucoma. Molecular analysis revealed a previously described pathogenic variant in the FOXC1 gene (c.378C > G p.I126M; rs104893958), in six affected patients which was not identified in two healthy siblings. Molecular analysis also revealed a PITX2 missense variant (c.28T > A p.L10M; rs755864040) which did not segregate with clinical findings and was considered likely benign. In conclusion, patients with ARS due to FOXC1 variants may present with glaucomatous optic nerve damage without apparent elevation in IOP. Normal-tension glaucoma is less commonly reported in individuals with ARS and a comprehensive glaucoma assessment may be warranted in these individuals even with normal IOP. These findings raise the possibility that glaucomatous damage associated with FOXC1 is not only due to high IOP.

Effects of Postural Variation on Intra-ocular Pressure: Comparison between Pseudo-exfoliation Glaucoma and Primary Open Angle Glaucoma.

Purpose: to compare the posture-related intraocular pressure (IOP) changes in pseudo-exfoliation glaucoma (PXFG) and in primary open-angle glaucoma (POAG) patients using the EyeOP, a novel Goldmann Applanation Tonometer (GAT) and to investigate the effect of ab externo trabeculectomy on these changes. Methods: Prospective, non-randomized, controlled, observational study. IOP was measured in sitting and in left lateral decubitus positions (LLDP), using GAT, GAT-EyeOP and Tonopen XL. Main Outcome Measure: Posture-related IOP differences between groups. Results: Thirty-two eyes of 32 PXFG patients (21 non-operated, 11 post-trabeculectomy) and 47 eyes of 47 POAG patients (18 non-operated, 29 post-trabeculectomy) were included. Among non-operated patients, the average increase in GAT IOP between positions (∆IOP) was 2 ± 1.86 mmHg for the PXFG group and 1.9 ± 2.84 mmHg for the POAG group (P = .87). The ∆IOP among operated patients (1.72 ± 1.9) was slightly less than in non-operated (1.6 ± 2.69; P = .905). Generally, in the LLDP, the mean difference between GAT and Tonopen XL IOP measurements was 1.9 ± 3.83 mmHg (r = 0.643; P < .001). A similar correlation was demonstrated between tonometers when measured in the sitting position. Conclusions: Both PXFG and POAG patients have increased IOP in LLDP as compared to an upright position, with no statistically significant difference between groups. Trabeculectomy had no significant effect on the ∆IOP. Abbreviations: PXFG: pseudo-exfoliation glaucoma; POAG: primary open-angle glaucoma; IOP: intraocular pressure; GAT: goldmann applanation tonometer; LLDP: left lateral decubitus position; ∆IOP: average increase in IOP between positions; TM: trabecular meshwork; CCT: central corneal thickness; MMC: Mitomycin C.

Transscleral Selective Laser Trabeculoplasty Without a Gonioscopy Lens.

PURPOSE OF THE STUDY: The purpose of the study was to investigate results of selective laser trabeculoplasty (SLT) performed directly on the sclera without a gonioscopy lens. DESIGN: Interventional case series, prospective, randomized, masked, controlled clinical trial. METHODS: Setting: Meir Medical Center, Kfar-Saba, Israel. STUDY POPULATION: Adults with uncontrolled primary open angle or pseudoexfoliation glaucoma randomized into 2 groups. INTERVENTION: The controls underwent conventional SLT with 100 spots delivered using a gonioscopy lens for 360 degrees of the trabecular meshwork. The study group underwent irradiation using the same parameters with the laser applications administered on the perilimbal sclera. Study visits: 1 hour, 1, 7, 30, 60, 180, and 365 days postprocedure. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) and side effects. RESULTS: Thirty adults were randomized into 2 groups. The mean (±SD) pretreatment IOP was 20.21±3.19 mm Hg for the study group (n=14) and 21.14±2.98 mm Hg for the controls (n=14; P =0.43), dropping to 15.50±3.77 and 15.00±4.08 mm Hg (P =0.74) after 6 months and to 16.00±3.31 and 14.00±2.45 mm Hg (P =0.22) after 12 months. The average IOP reduction after 6 and 12 months was 23.4% and 20.83% for the study group and 27.1% and 33.77% for the controls (P=0.528). Success (a decrease of ≥15% at 6 months with no additional medications, laser, or glaucoma surgery) was achieved in 12 (85.7%) study patients and 9 (69.2%) controls (P=0.385). Complications were mild and transient (n=30), although significantly higher in the controls (n=15; P <0.0001). CONCLUSIONS: SLT applied directly to the perilimbal sclera may be as efficacious as the conventional procedure for 1 year.

Anterior segment imaging in glaucoma: An updated review.

Anterior segment imaging allows for an objective method of visualizing the anterior segment angle. Two of the most commonly used devices for anterior segment imaging include the anterior segment optical coherence tomography (AS-OCT) and the ultrasound biomicroscopy (UBM). AS-OCT technology has several types, including time-domain, swept-source, and spectral-domain-based configurations. We performed a literature search on PubMed for articles containing the text "anterior segment OCT," "ultrasound biomicroscopy," and "anterior segment imaging" since 2004, with some pertinent references before 2004 included for completeness. This review compares the advantages and disadvantages of AS-OCT and UBM, and summarizes the most recent literature regarding the importance of these devices in glaucoma diagnosis and management. These devices not only aid in visualization of the angle, but also have important postsurgical applications in bleb and tube imaging.

Ocular anterior segment changes in pregnancy.

PURPOSE: To evaluate the changes occurring in the cornea, anterior segment anatomy, and intraocular pressure (IOP) in pregnant women. SETTING: Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin, Israel. DESIGN: Prospective single-center comparative study. METHODS: The Ocular Response Analyzer dynamic bidirectional applanation device and the Pentacam HR Scheimpflug imaging system were used to obtain data on the anterior eye segments of healthy pregnant and nonpregnant women. RESULTS: Sixty pregnant and 60 nonpregnant women were enrolled. The Goldmann-correlated IOP and corneal-compensated IOP were significantly lower in the pregnant group (mean 10.96 mm Hg versus 12.97 mm Hg, P<.001; and 10.97 mm Hg versus 13.16 mm Hg, P<.001, respectively). The corneal front steep keratometry value was statistically significantly higher in the pregnant group (44.81 diopters [D] versus 44.1 D, P=.039). No significant difference was found in corneal hysteresis, the corneal resistance factor, corneal posterior curvature, central corneal thickness and volume, anterior chamber depth and volume, or iridocorneal angle. CONCLUSIONS: Pregnancy was associated with greater corneal curvature and lower IOP. Further studies should be performed to learn whether these alterations result from changes in corneal biomechanical properties during pregnancy. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Digoxin derivatives with enhanced selectivity for the α2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.

In the ciliary epithelium of the eye, the pigmented cells express the α1ß1 isoform of Na,K-ATPase, whereas the non-pigmented cells express mainly the α2ß3 isoform of Na,K-ATPase. In principle, a Na,K-ATPase inhibitor with selectivity for α2 could effectively reduce intraocular pressure with only minimal local and systemic toxicity. Such an inhibitor could be applied topically provided it was sufficiently permeable via the cornea. Previous experiments with recombinant human α1ß1, α2ß1, and α3ß1 isoforms showed that the classical cardiac glycoside, digoxin, is partially α2-selective and also that the trisdigitoxose moiety is responsible for isoform selectivity. This led to a prediction that modification of the third digitoxose might increase α2 selectivity. A series of perhydro-1,4-oxazepine derivatives of digoxin have been synthesized by periodate oxidation and reductive amination using a variety of R-NH2 substituents. Several derivatives show enhanced selectivity for α2 over α1, close to 8-fold in the best case. Effects of topically applied cardiac glycosides on intraocular pressure in rabbits have been assessed by their ability to either prevent or reverse acute intraocular pressure increases induced by 4-aminopyridine or a selective agonist of the A3 adenosine receptor. Two relatively α2-selective digoxin derivatives efficiently normalize the ocular hypertension, by comparison with digoxin, digoxigenin, or ouabain. This observation is consistent with a major role of α2 in aqueous humor production and suggests that, potentially, α2-selective digoxin derivatives could be of interest as novel drugs for control of intraocular pressure.

Corneal collagen cross-linking for the treatment of progressive keratoconus: 3-year prospective outcome.

OBJECTIVE: To assess the long-term effects of treatment of progressive keratoconus with ultraviolet A-riboflavin collagen cross-linking (CXL). DESIGN: This was a prospective clinical study. PARTICIPANTS: Seventeen eyes of 17 patients with progressive keratoconus were treated with CXL. METHODS: Patients were examined preoperatively, at week 1, months 1, 3, 6, 9, 12, 24, and 36 after treatment. We assessed uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA), refraction, biomicroscopy and fundus appearance, intraocular pressure, endothelial cell density (ECD), corneal topography, minimal corneal thickness (MCT), macular optical coherence tomography, axial length, and corneal biomechanics with the ocular response analyzer. RESULTS: Comparing the 36-month time point results with pretreatment values, we found that UCVA and BSCVA were unchanged. Steepest meridian keratometry (D) and mean cylinder (D) did not show significant change compared with pretreatment values but showed a slight increase as compared with the 24-month time point (53.9 vs 51.7 vs 52.5, and 10.5 vs 8.1 vs 9.2 before, at 24 months, and at 36 months, respectively). Axial length (mm) showed an elongation trend throughout the follow-up period (24.56 vs 24.61 [p = 0.04] vs 24.71 [p = 0.05], before, at 24 months, and at 36 months, respectively). No significant change was observed in ECD, corneal hysteresis and corneal resistance factor, MCT, or foveal thickness. CONCLUSIONS: Three-year results after CXL show stable visual acuity, stable corneal thickness, and stable corneal biomechanical parameters. The decreasing trend in keratometry values that was observed during the first 2 years after CXL was no longer evident. Longer follow-up is needed to decide whether it is a first sign of loss of achieved stability and resumption of keratoconus progression.

Measurement of the difference in intraocular pressure between the sitting and lying body positions in healthy subjects: direct comparison of the Icare Pro with the Goldmann applanation tonometer, Pneumatonometer and Tonopen XL.

BACKGROUND: Change in intraocular pressure is known to occur with body posture. Previously, markedly different estimations of this change were reported. The Icare Pro (Icare; Tiolat Oy, Helsinki, Finland) is designed to measure intraocular pressure with the subject supine. We compared the measurement of postural change in intraocular pressure obtained with this and 3 other tonometers: Goldmann applanation tonometer (CSO, Firenze, Italy), Pneumatonometer (Model 30, Reichert, Depew, NY, USA) and the Tonopen XL (Reichert). DESIGN: Prospective comparative study. PARTICIPANTS: Twenty-one healthy subjects. METHODS: Intraocular pressure was measured in random order with four tonometers, first sitting then after 10 min of lying. MAIN OUTCOME MEASURES: Average postural intraocular pressure change (mmHg) and the 95% limits of agreement for measuring postural intraocular pressure change between tonometers. RESULTS: Average postural intraocular pressure change (lying minus sitting, mmHg) was measured highest with the Goldmann applanation tonometer (4.1 ± 2.6) and Pneumatonometer (3.9 ± 2.1), significantly lower with the Tonopen (0.9 ± 1.7) and was negative with the Icare (-0.9 ± 3.3). The 95% limits of agreement for measuring postural intraocular pressure change between Goldmann applanation tonometer and Icare, Pneumatonometer and Tonopen were -3.2-13.3, -6.4-6.9 and -2.8-9.4 mmHg, respectively. CONCLUSIONS: Postural change in intraocular pressure was measured similarly, on average, with Goldmann applanation tonometer and Pneumatonometer, and much lower with Tonopen and Icare Pro. There was poor interdevice agreement in measuring this parameter. We observed high intersubject variability, suggesting the clinical importance of this measurement in the diagnosis and management of glaucoma.