Modification of a Selective NTRK2 Agonist and Confirmation of Activity in a Glaucoma-on-a-Chip Model.

Purpose: RNYK is a selective agonist of the neurotrophic tyrosine kinase receptor type 2 (NTRK2) which has been screened from a phage-displayed peptide library. Its sequence is SGVYKVAYDWQH, similar to a native NTRK2 ligand, that is, brain-derived neurotrophic factor (BDNF). The current study was performed to recognize and confirm critical residues for RNYK activity in a glaucoma-on-a-chip model. Methods: We designed a modified RNYK (mRNYK) peptide based on hotspots of the RNYK sequence identified by alanine scanning. The critical residues consisted of tyrosine, valine, aspartic acid, and tryptophan (YVDW); however, lysine and glutamine were also maintained in the final sequence (YKVDWQ) for forming amide bonds and peptide dimerization. The affinity of mRNYK binding was confirmed by testing against NTRK2 receptors on the surface of ATRA-treated SH-SY5Y cells. The neuroprotective effect of mRNYK was also evaluated in cell culture after elevated pressure insult in a glaucoma-on-a-chip model. Results: The primary amine on the lysine side-chain from one sequence (YKVDWQ) reacted with a γ-carboxamide group of glutamine from the other sequence, forming dimeric mRNYK. In silico, molecular dynamic simulations of the mRNYK-NTRK2 complex showed more stable and stronger interactions as compared to the RNYK-NTRK2 complex. In vitro, mRNYK demonstrated a neuroprotective effect on SH-SY5Y cells under normal and elevated pressure comparable to RNYK. The 50% effective concentration (logEC50) for mRNYK was 0.7009, which was better than RNYK with a logEC50 of 0.8318. Conclusion: The modified peptide studied herein showed improved stability over the original peptide (RNYK) and demonstrated potential for use as a BDNF agonist with neuroprotective properties for treatment of neurodegenerative disorders such as glaucoma.

Capsulectomy Shunt Revision versus Repeat Shunt Implantation Following Ahmed Glaucoma Valve Failure in Refractory Glaucoma.

PURPOSE: To investigate the efficacy of capsulectomy shunt revision (CSR) compared with the implantation of a second Ahmed glaucoma valve (re-AGV) in glaucoma patients with failed shunts. DESIGN: Quasi-experimental study. SUBJECTS: Forty-six eyes with failed Ahmed glaucoma valves (AGVs) were included in the study; 25 underwent CSR, whereas 21 underwent re-AGV. METHODS: Patients were scheduled for CSR or re-AGV based on the appearance and accessibility of the existing AGV versus the feasibility for re-AGV in other quadrants. The CSR involved incision and dissection down to the thick fibrous capsule around the AGV plate, which was excised extensively. For re-AGV, the second shunt was implanted in the supranasal or infranasal quadrants. MAIN OUTCOME MEASURES: Surgical success, defined as intraocular pressure (IOP) > 5 mmHg, ≤ 21 mmHg, IOP reduction ≥ 20% from baseline, and no reoperation for glaucoma. Secondary outcome measures were IOP, number of glaucoma medications, and complications during a 12-month follow-up period. RESULTS: Mean IOP was significantly lower than preoperative values at all time points in both study groups (P < 0.001). Intraocular pressure decreased significantly from 28.3 ± 5.04 mmHg at baseline to 16.4 ± 2.4 mmHg at final follow-up in the capsulectomy group (P = 0.002). Corresponding IOP values for re-AGV were 30.99 ± 6.2 and 13.6 ± 3.8 mmHg, respectively (P = 0.001). Intraocular pressure in the CSR group was higher than re-AGV during the study (P = 0.003). The cumulative probability of success at 12 months was significantly higher in the re-AGV group (87.5% vs 53.3%, P = 0.002). There was no significant difference in the number of glaucoma medications and overall complications rate between the study groups. Wound leakage was the only complication more common in the CSR group (P = 0.012). CONCLUSION: In the eyes with a failed AGV, re-AGV and CSR are both effective. Implantation of a second shunt seems more effective than the surgical revision of an existing device; however, the latter procedure may be a viable option in selected cases. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Trabeculotomy Versus Combined Trabeculotomy-Trabeculectomy for Management of Primary Congenital Glaucoma.

PRCIS: Trabeculotomy (T) alone is as safe and effective as combined trabeculotomy-trabeculectomy (TT) in patients with primary congenital glaucoma (PCG) and requires significantly fewer examinations under anesthesia in the postoperative period. PURPOSE: The purpose of this study was to compare the outcomes of T and combined TT as the initial surgical procedure for patients with PCG. METHODS: In this retrospective study, medical records of patients who had undergone T or TT as the initial procedure for PCG were reviewed. The primary outcome measure was a surgical success, defined as 5≤ intraocular pressure (IOP) ≤21 mm Hg, IOP reduction of at least 20% with no need for further glaucoma surgery. Secondary outcome measures were the number of glaucoma medications and complications. RESULTS: A total of 134 eyes from 134 patients with a mean follow-up of 8±6.6 years were included consisting of 106 and 28 eyes, which had undergone T and TT, respectively. Success rates were comparable with both surgical procedures at 1, 2, 3, 4, and 5 years with no statistically significant difference. IOP was significantly decreased from 27.5±4.2 mm Hg preoperatively to 15.62±3.4 mm Hg at the 5-year follow-up visit in the T group and from 25.3±6.5 to 17.1±3.2 mm Hg in the TT group (P=0.1) there was no significant difference between the 2 groups in the number of glaucoma medications (P=0.2). Patients in the T group required significantly fewer examinations under anesthesia than the TT group (7.3±4.4 vs. 10.1±3.9, P=0.04). CONCLUSION: Trabeculotomy alone seems as effective as combined trabeculotomy-trabeculectomy and may significantly reduce exposure to anesthesia in primary congenital glaucoma patients.

Risk of Missed Diagnosis of Primary Open-Angle Glaucoma by Eye Care Providers.

Purpose: To evaluate the efficacy of opportunistic case finding in glaucoma detection and to determine factors associated with failure of glaucoma detection by eye health providers. Methods: This study was conducted on 154 new definite primary open-angle glaucoma (POAG) patients presenting to our glaucoma clinic. A questionnaire was prepared to determine if these subjects had sought eye care up to 12 months before presentation. The type of eye care provider and the principal reason for the visit were probed. The primary outcome measure was the frequency of a correct glaucoma diagnosis in their index visit. The secondary outcomes were factors associated with missed POAG diagnosis. Results: The great majority of study subjects (132 cases, 85.7%) had sought at least one ocular examination within 1 year before presentation. Among these patients, 73 cases (55.3%) had remained undiagnosed after the examination. Among the probed variables, age, gender, visual acuity, visual field defects, intraocular pressure, cup/disc ratio, nerve fiber layer thickness of the worse eye at presentation, and family history of glaucoma were comparable between correctly diagnosed and missed POAGs. The only factors significantly associated with missed POAG diagnosis were lack of significant refractive errors and visiting an optometrist rather than an ophthalmologist. Conclusions: The efficacy of opportunistic case finding for POAG seems to be less than ideal in our settings. Lack of a significant refractive error and visiting an optometrist rather than an ophthalmologist were associated with a missed diagnosis of POAG. These observations reflect the need to adopt policies to improve glaucoma screening by eye care providers.

The Influence of Near Vision Tasks on Intraocular Pressure in Normal Subjects and Glaucoma Patients.

Purpose: To investigate the effect of static accommodative tasks on intraocular pressure (IOP) of glaucomatous and normal eyes. Methods: Four groups of subjects categorized as primary open-angle glaucoma (POAG), primary angle-closure suspects (PACS), normal age-matched controls, and normal young adults (NYA; age < 40 years) were enrolled. The baseline IOPs were measured after the subjects were looking at a distant target for 15 min. Static accommodation was obtained by execution of near vision tasks (reading at 33 cm in daylight [300 lux] for 60 min). IOPs were measured at 15, 30, 45, and 60 min intervals while accommodating and then measured again after 15 min of relaxing accommodation while looking at a distant target. Results: One-hundred and eighteen eyes of 98 subjects were recruited. The study groups consisted of the following categories: 25 POAG (46 eyes), 24 PACS (47 eyes), 25 matched controls (50 eyes), and 24 NYA (48 eyes). Within all groups, the mean IOP decreased throughout the accommodation period at all time points. Maximum IOP reduction after accommodation was detected at the 30-min time among the POAG subjects, at the 45-min time in the PACS and matched control groups, and at 15 min after the relaxation of accommodation in the NYA group. IOP reduction levels showed no statistically significant difference among POAG, PACS, and the normal matched groups in their response to accommodation. However, NYA had significantly lower IOP and greater IOP reduction after the resting period (relaxation of accommodation). Conclusion: Static accommodative tasks can significantly reduce IOP in normal, POAG, and PACS individuals. Encouraging glaucoma patients to practice periodical near vision tasks could be viewed as an adjunctive measure for glaucoma management.

Prenatal diagnosis of primary congenital glaucoma and histopathological features in a fetal globe with cytochrome p4501B1 mutations.

BACKGROUND/OBJECTIVES: This study aims to report the developmental and histopathological features of ocular tissues from an electively aborted human fetus with mutations in cytochrome p4501B1, and thus predisposed to primary congenital glaucoma in comparison to an age-matched healthy fetal globe. SUBJECTS/METHODS: Both eyes of two 17-week gestational aged fetuses, the first with CYP1B1 mutations and the second as healthy control fetus, were studied. Hematoxylin and eosin, Periodic acid-Schiff, Gomori's trichrome, and Verhoeff-Van Gieson staining protocols in addition to immunohistochemistry staining using anti-cytochrome p4501B1, anti-fibrillin-1, and anti-4-hydroxy-2-nonenal antibodies, as primary antibodies, were performed to assess the effect of the mutations on tissue development, cytochrome p4501B1 protein expression, extracellular matrix structure, and oxidative stress in the developing fetus eye. Quantitative analyses were performed using ImageJ software. Student's t-test was used for statistical analysis and P-values <0.05 were considered as significant. RESULTS: Delayed development in ocular tissues, decreased expression of cytochrome p4501B1 protein, irregular extracellular matrix structure, and increased oxidative stress biomarker were evident in the ocular tissues of the fetus with cytochrome p4501B1 mutations as compared to a normal globe from an age-matched fetus. CONCLUSION: To the best of our knowledge, this is the first report of prenatal diagnosis of primary congenital glaucoma. We also describe histopathological changes in the primary congenital glaucoma-affected globes revealing the effect of cytochrome p4501B1 deficiency on ocular tissues during early fetal development contributing to the glaucoma phenotype.

Intraocular Pressure Changes in the Contralateral Eye After Glaucoma Surgery.

PRCIS: Glaucoma surgery in 1 eye can result in significant intraocular pressure (IOP) elevation in the fellow eye in a significant percentage of subjects. This effect is more pronounced following glaucoma drainage device implantation and in subjects developing postoperative hypotony in the first eye. PURPOSE: The aim was to investigate the course and magnitude of IOP changes in contralateral eyes following glaucoma surgery. PATIENTS AND METHODS: We studied 131 glaucoma patients undergoing surgery. IOP changes in fellow eyes and the number of glaucoma medications were recorded for 6 months. Both normal and glaucomatous fellow eyes were included. Patients on preoperative acetazolamide were analyzed separately. IOP change ≥4 mm Hg or 20% increase from baseline values was considered significant. RESULTS: Baseline IOP in fellow eyes was 13.1±3.3 mm Hg which increased significantly at all-time points with a peak at 1 week (mean increase: 3.1±3.2 mm Hg) gradually decreasing up to 6 months (mean increase 0.9±2.1 mm Hg). The number of fellow eyes with clinically significant IOP elevation at 1 day, 1 week, and 1, 3. and 6 months was 47, 76, 47, 31, and 37 showing mean IOP rise of 4.5±2.3 (38.5%), 5.4±1.8 (48.5%), 4.8±1.6 (44.2%), 3.7±1.3 (36.5%), and 3.2±1.3 (32.6%) mm Hg, respectively. Medications were added to 18 fellow eyes (including 10 initially "normal" eyes) while 7 other fellow eyes required surgery.Significant IOP elevation in fellow eyes was associated with tube shunt surgery (P<0.008 at all-time points), a diagnosis of glaucoma following cataract surgery, IOP ≤5 mm Hg on the first postoperative day (P=0.002) and use of preoperative acetazolamide. CONCLUSION: Glaucoma surgery was associated with IOP elevation in fellow eyes in a significant number of subjects and suggests that IOP in the unoperated eye should also be checked at postoperative visits.

Efficacy and safety of timolol-dorzolamide fixed-combination three times a day versus two times a day in newly diagnosed open-angle glaucoma.

OBJECTIVE: This study aimed to compare the therapeutic efficacy and safety of dorzolamide/timolol fixed-combination(Cosopt) in newly diagnosed primary open-angle glaucoma (POAG) patients. METHODS: In this prospective, interventional case series, newly POAG patients were included. Patients were started on Cosopt twice a day (BID) for one month and then switched to three times a day (TDS) for an additional month. Patients underwent comprehensive ophthalmic examination, diurnal intraocular pressure (IOP), blood pressure (BP), and 24-h heart rate (HR) measurements at baseline, month 1(BID), and month 2(TDS). Throughout the study, all adverse events were monitored by the investigators. RESULTS: In 31 POAG patients that completed the study, the mean baseline IOP was 23.1 ± 3.15 mmHg. IOP was decreased significantly 16.5 ± 2.21 at one month (p < .0001) and 13.9 ± 2.23 mmHg at 1 and 2 months follow up (p < .0001). IOP was significantly lower in month 2 compared to month 1 (p = .0004). While Cosopt BID significantly reduced the mean 24-h systolic BP and mean 24-h HR from baseline (p < .0001), the mean 24-h systolic BP and HR remained unchanged with Cosopt TDS compared to BID (p = .62). CONCLUSIONS: Cosopt TDS has a superior IOP-lowering effect than Cosopt BID in POAG patients with comparable safety profiles.

Systemic supplemental oxygen therapy during accelerated corneal crosslinking for progressive keratoconus: randomized clinical trial.

PURPOSE: To investigate the potential additive effect of systemic supplemental oxygen administered during accelerated corneal crosslinking (CXL) for progressive keratoconus (KC). SETTING: Academic center. DESIGN: Randomized clinical trial. METHODS: Eyes with progressive KC randomized to 3 different CXL protocols were included. The first group (OA-CXL) included 19 eyes that underwent an accelerated CXL protocol (9 mW/cm2 for 10 minutes) while receiving systemic oxygen at a rate of 5 L/min for 10 minutes. The second group consisted of 14 eyes undergoing the same accelerated CXL protocol without supplemental oxygen therapy (A-CXL). The third group (C-CXL) comprised 14 eyes undergoing conventional CXL according to the Dresden protocol. All subjects were followed up for at least 6 months. Visual acuity, keratometry and corneal biomechanical parameters including corneal hysteresis and corneal resistance factor (CRF) were measured preoperatively and 6 months postoperatively. RESULTS: Reduction in maximum keratometry (Kmax) was significantly greater in the OA-CXL group (P = .01). At baseline, the mean Kmax was 54.31 ± 3.64 diopters (D) in the OA-CXL group, 54.66 ± 4.99 D in the A-CXL group, and 56.03 ± 5.28 D in the C-CXL group (P = .58), which reached 53.58 ± 3.24 D, 54.59 ± 4.65 D, and 55.87 ± 4.73 D at 6 months in the 3 study groups, respectively (P = .115). The mean CRF increased significantly only in the OA-CXL group from a baseline value of 6.32 ± 2.12 mm Hg to 7.38 ± 1.88 mm Hg at 6 months (P = .009). CONCLUSIONS: This study suggests superior efficacy of an accelerated CXL protocol coupled with systemic oxygen supplementation when compared with the accelerated CXL protocol and the conventional protocol in eyes with progressive KC. In addition to greater reduction in Kmax as the primary outcome, improvement in corneal biomechanics was also observed at 6 months.

Laminar and Prelaminar Tissue Characteristics of Glaucomatous Eyes Using Enhanced Depth Imaging OCT.

PURPOSE: To investigate characteristics of the lamina cribrosa (LC) and prelaminar tissue (PLT) in eyes of patients with primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG), and pseudoexfoliation glaucoma (PXG) using enhanced depth imaging (EDI) OCT. DESIGN: Observational case-control study. PARTICIPANTS: A total of 116 eyes from 116 participants with POAG (n = 30 eyes), PACG (n = 29 eyes), or PXG (n = 29 eyes) and 28 healthy eyes. METHODS: Participants underwent a complete ophthalmologic examination in addition to corneal pachymetry, standard achromatic perimetry, peripapillary retinal nerve fiber layer (RNFL) OCT, and EDI OCT, as well as measurement of LC, PLT thickness, and LC depth. MAIN OUTCOME MEASURES: Lamina cribrosa measurement, PLT thickness, and LC thickness. RESULTS: Average LC thickness was significantly different among the 4 groups with the thinnest values in the PXG group. Prelaminar tissue also was significantly thinner in PXG eyes. The POAG eyes demonstrated the largest LC depths (P < 0.05), whereas PACG and healthy eyes demonstrated the smallest LC depths (P < 0.05). Mean deviation on standard achromatic perimetry and average thickness on peripapillary RNFL OCT were associated significantly with LC and PLT thickness. CONCLUSIONS: Pseudoexfoliation glaucoma eyes demonstrate reduced LC and PLT thickness compared with POAG, PACG, and healthy eyes. Lamina cribrosa depth was larger in POAG eyes as compared with PXG, PACG, and healthy eyes. These findings may account for the peculiar appearance of the optic nerve head in PXG eyes.

A lab-on-a-chip model of glaucoma.

AIMS: We developed a glaucoma-on-a-chip model to evaluate the viability of retinal ganglion cells (RGCs) against high pressure and the potential effect of neuroprotection. METHODS: A three-layered chip consisting of interconnecting microchannels and culture wells was designed and fabricated from poly-methyl methacrylate sheets. The bottom surface of the wells was modified by air plasma and coated with different membranes to provide a suitable extracellular microenvironment. RGCs were purified from postnatal Wistar rats by magnetic assisted cell sorting up to 70% and characterized by flow cytometry and immunocytochemistry. The cultured RGCs were exposed to normal (15 mmHg) or elevated pressure (33 mmHg) for 6, 12, 24, 36, and 48 hr, with and without adding brain-derived neurotrophic factor (BDNF) or a novel BDNF mimetic (RNYK). RESULTS: Multiple inlet ports allow culture media and gas into the wells under elevated hydrostatic pressure. PDL/laminin formed the best supporting membrane. RGC survival rates were 85%, 78%, 70%, 67%, and 61% under normal pressure versus 40%, 22%, 18%, 12%, and 10% under high pressure at 6, 12, 24, 36, and 48 hr, respectively. BDNF and RNYK separately reduced RGC death rates about twofold under both normal and elevated pressures. CONCLUSION: This model recapitulated the effects of elevated pressure over relatively short time periods and demonstrated the neuroprotective effects of BDNF and RNYK.

Lower- and higher-order aberrations after photorefractive keratectomy with and without compensation of pupil centroid shift: fellow eye comparison.

PURPOSE: To study the effect of pupil centroid shift (PCS) compensation on lower- and higher-order aberrations (HOAs) after photorefractive keratectomy (PRK). SETTING: Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. DESIGN: Prospective intrasubject fellow eye study. METHODS: One hundred twelve eyes of 56 patients with simple myopia or myopic astigmatism scheduled for PRK were enrolled. Preoperatively, the amount of PCS was measured in the horizontal and vertical directions. All eyes received wavefront-optimized treatment with static cyclotorsion compensation. PCS compensation was turned on for the right eye of each subject (PCS-on group), and turned off for the left eye (PCS-off group). Postoperatively, refraction and corneal HOAs were compared between the study groups at 6 months. RESULTS: Mean preoperative myopia was -3.84 diopters (D) ± 2.41 (SD) vs -3.75 ± 2.27 D (P = .408), whereas mean preoperative cylinder was -1.18 D ± 1.15 (SD) vs -1.14 ± 1.16 D (P = .769) in the PCS-on and PCS-off groups, respectively. Mean absolute PCS values were 62.25 µm ± 41.82 (SD) vs 55.92 ± 37.47 µm (P = .45) in the horizontal direction and 65.04 ± 47.16 µm vs 58.40 ± 45.44 µm in the vertical direction (P = .29) in the PCS-on and PCS-off groups, respectively. The study groups were comparable in terms of postoperative refraction and root mean square of total corneal HOAs. CONCLUSIONS: Compensation of PCS did not affect lower- and higher-order aberrations after wavefront-optimized PRK with static cyclotorsion compensation in myopic or myopic astigmatic eyes.

Intraorbital Steroid Injection for Active Thyroid Ophthalmopathy.

PURPOSE: To evaluate the effect of orbital steroid injections in patients with active thyroid ophthalmopathy resistant to or dependent on systemic steroids, or with complications related to systemic steroid use. METHODS: This prospective non-comparative case series includes 31 eyes of 17 patients with active thyroid ophthalmopathy and clinical activity score (CAS) of 3 or more, without compressive optic neuropathy or overt exposure keratopathy. All subjects had a history of previous systemic steroid use (with steroid resistance or dependence) or had developed complications related to steroids. A combination of steroids including triamcinolone acetonide 20 mg and dexamethasone 4 mg was injected in the upper and lower retroseptal orbital spaces three or four times at one-month intervals. The patients were examined periodically after each injection and at least three months after the last injection. RESULTS: Mean pre-injection CAS was 5.2 ± 1.3 which was improved to 1.6 ± 1 after the fourth injection (P < 0.001). Upper and lower lid retraction improved in 100% and 68.2% of the affected eyes, respectively. Strabismus completely resolved in one of five affected patients and the most significant improvement was observed in supraduction. Mean improvement in exophthalmos was 1.2 ± 1.1 mm. Visual acuity did not significantly change after the injections. Eyelid ecchymosis and/or subconjunctival hemorrhage was observed in 7.1% and intraocular pressure rise occurred in 8.8% of eyes. CONCLUSION: Orbital steroid injections can be used for the treatment of active thyroid ophthalmopathy when the patient is resistant to or dependent on systemic steroids or has developed complications of systemic steroids.

Congenital Four Eyelid Ectropion Associated With Clefting Anomaly.

An infant with congenital 4 eyelid ectropion associated with cleft lip and palate developed exposure keratopathy. He underwent skin grafting of the upper eyelids and lateral canthal reconstruction. Ectropion and signs of exposure keratopathy improved. Congenital eyelid ectropion is a rare disorder. Surgical repair can successfully correct the condition.

Trichloroacetic acid 10% injection for treatment of conjunctival inclusion cysts.

Purpose: To evaluate the effect of intra-lesional injection of Trichloroacetic acid (TCA) 10% in patients with conjunctival inclusion cysts.Methods: This prospective case series study included all patients with conjunctival inclusion cyst who were referred to our referral center from August 2016 to August 2018. All patients received TCA 10% injection into the conjunctival cyst, and outcomes of the intervention were evaluated at least 6 months later.Results: Ten patients with mean age of 24 ± 17.6 (range 6-65) years including three children received TCA 10% injection into the conjunctival cyst. We included 6 anophthalmic and 4 ophthalmic cases. All patients were treated successfully and no recurrence of the lesion was observed in any case. Mean follow up duration was 18.1 ± 8.3 (range 6-28) months.Conclusion: Intra-lesional injection of TCA 10% is a safe, simple, and effective treatment in patients with conjunctival inclusion cysts including ophthalmic cases and anophthalmic cases, both in adults and in children. This concentration may avoid ocular surface complications.

Trans-iris fixation of dislocated in-the-bag intraocular lenses.

PURPOSE: The aim of this article is to describe the safety and efficacy of trans-iris suture fixation for the management of late dislocation of in-the-capsular-bag intraocular lenses following uncomplicated cataract surgery. PATIENTS AND METHODS: Eleven eyes of 11 patients with late in-the-capsular-bag intraocular lens dislocation following uneventful phacoemulsification cataract surgery were recruited in the study. The dislocated intraocular lens-capsular bag complex was sutured to the iris at two points 180° apart using 9-0 polypropylene sutures on long needles. RESULTS: Mean patient age was 67 ± 6 years. Seven eyes had pseudoexfoliation syndrome, one eye had Marfan syndrome, and another eye had a traumatic cataract; no risk factor was identified for intraocular lens dislocation in two eyes. A capsular tension ring had been implanted during cataract surgery in four eyes. In six eyes, the posterior chamber intraocular lenses were one-piece foldable while the remaining were three-piece intraocular lenses. Compared to the preoperative value, corrected distance visual acuity was significantly improved postoperatively (p < 0.005). Intraoperative hyphema occurred in two eyes. Pupil ovalization was observed in all eyes. Mean endothelial cell count decreased by 4 ± 1.7% after intraocular lens fixation. The capsular bag-intraocular lens complex was stable and well-centered in the pupillary area in all eyes at the final follow-up examination which was performed 16 ± 4 months postoperatively. CONCLUSION: Trans-iris fixation is a simple and effective procedure for management of late intraocular lenses-capsular bag complex dislocation, without major complications.

Identification of genes involved in glaucoma pathogenesis using combined network analysis and empirical studies.

Glaucoma is a leading cause of blindness. We aimed in this study to identify genes that may make subtle and cumulative contributions to glaucoma pathogenesis. To this end, we identified molecular interactions and pathways that include transcription factors (TFs) FOXC1, PITX2, PAX6 and NFKB1 and various microRNAs including miR-204 known to have relevance to trabecular meshwork (TM) functions and/or glaucoma. TM tissue is involved in glaucoma pathogenesis. In-house microarray transcriptome results and data sources were used to identify target genes of the regulatory molecules. Bioinformatics analyses were done to filter TM and glaucoma relevant genes. These were submitted to network-creating softwares to define interactions, pathways and a network that would include the genes. The network was stringently scrutinized and minimized, then expanded by addition of microarray data and data on TF and microRNA-binding sites. Selected features of the network were confirmed by empirical studies such as dual luciferase assays, real-time PCR and western blot experiments and apoptosis assays. MYOC, WDR36, LTPBP2, RHOA, CYP1B1, OPA1, SPARC, MEIS2, PLEKHG5, RGS5, BBS5, ALDH1A1, NOMO2, CXCL6, FMNL2, ADAMTS5, CLOCK and DKK1 were among the genes included in the final network. Pathways identified included those that affect ECM properties, IOP, ciliary body functions, retinal ganglion cell viability, apoptosis, focal adhesion and oxidative stress response. The identification of many genes potentially involved in glaucoma pathology is consistent with its being a complex disease. The inclusion of several known glaucoma-related genes validates the approach used.