Marfan syndrome is an autosomal dominant genetic connective tissue disorder that results from mutations in the fibrillin-1 gene located on chromosome band 15q 15–21. Fibrillin, a glycoprotein, is widely expressed throughout the body and contribute to elasticity and force-bearing capacity of connective tissue. In the eye, fibrillin is a key constituent of the ciliary zonules, which suspend the crystalline lens in place. The zonular defect leads to ectopia lentis that is hallmark of Marfan ocular abnormalities and occurs in 60 to 80% of cases. Other less common ocular features of Marfan syndrome are increased axial length, astigmatism, and flat cornea. Visual function in Marfan syndrome could be affected in several ways: ectopia lentis, refractive error, amblyopia, retinal detachment, cataract, and glaucoma. Management of subluxated lens starts with correction of refractive error with eyeglasses in mild cases. In more severe cases, especially when lens bisects the pupil, complete correction of refractive error is impossible without removing subluxated lens. The best method for visual rehabilitation after lens extraction is still debated. Aphakic Artisan implantation at the time of subluxated lens removal results in good visual outcomes with acceptable safety profile. Studies with longer term follow up and larger sample populations are needed to evaluate the safety of this procedure in patients with Marfan syndrome.

Glucosamine is the most common nutrition supplement used in the United States. It is promoted not only as a pain reliever but also a therapy to slow osteoarthritis. Although studies with 3,800 patients with osteoarthritis of the knee or hip found that glucosamine was no better than placebo, it continues to be used for these two indications due to its perceived safety. However, reports of an increased intraocular pressure are alarming, especially in glaucoma. Glycosaminoglycans play a key role in the physiology of the cornea, conventional outflow of aqueous humor and the retina. In theory, long-term treatment with glucosamine could reach a concentration that impacts the morphology and function of ocular tissues. We recommend ophthalmologists counsel glaucoma patients about the potential risks of glucosamine and encourage cessation in uncontrolled intraocular pressure.

Purpose: To compare the therapeutic efficacy and safety of dorzolamide/timolol fixed-combination in newly diagnosed primary open angle glaucoma patients. Methods: In this prospective, interventional case series, newly diagnosed primary open angle glaucoma (POAG) patients that had not been treated for glaucoma were included. Patients were started on Cosopt twice a day (BID) for 1 month and then switched to three times a day (TDS) for additional 1 month. Patients underwent comprehensive ophthalmic examination, diurnal intraocular pressure (IOP), blood pressure (BP) and 24-hours heart rate (HR) measurements at baseline, month 1( BID), and month 2( TDS). IOP, systolic and diastolic pressures were measured at 8:00 AM,12:00 AM, 4:00 PM, 8:00 PM and 12:00 PM. Throughout the study, all adverse events were recorded and monitored by the investigators. Results: In 31 POAG patients that completed the study ,mean baseline IOP was 23.1±3.15 mmHg . IOP was decreased significantly 16.5 ± 2.21 at 1 month (P < 0.0001) and 13.9 ± 2.23 mmHg at 1 and 2 month follow up. (P < 0.0001) IOP was significantly lower in month 2 compared to month 1 (P = 0.0004). While Cosopt BID significantly reduced the mean 24-hour systolic BP and mean 24-hour HR from baseline (P < 0.0001), the mean 24-hour systolic BP and HR remained unchanged 2ith Cosopt TDS compared to BID (P = 0.62). Conclusions: Cosopt TDS has a superior IOP-lowering effect than Cosopt BID in POAG patients with comparable safety profile.

Purpose: To investigate the relationship of lamina cribrosa displacement to corneal biomechanical properties and visual function after mitomycin C-augmented trabeculectomy. Method: Eighty-one primary open angle eyes were imaged before and after trabeculectomy using an enhanced depth spectral-domain optical coherence tomography (SDOCT). Corneal biomechanical properties were measured with the Ocular Response Analyser before the surgery. The anterior lamina cribrosa (LC) was marked at several points in each of six radial scans to evaluate LC displacement in response to Intraocular pressure (IOP) reduction. A Humphrey visual field test (HVF) was performed before the surgery as well as three and six months postoperatively. Results: Factors associated with a deeper baseline anterior lamina cribrosa depth (ALD) were cup-disc ratio (P=0.04), baseline IOP (P= 0.01), corneal hysteresis (P= 0.001), and corneal resistance factor (P= 0.001). After the surgery, the position of LC became more anterior (negative), posterior (positive) or remained unchanged. The mean LC displacement was -42 μm (P= 0.001) and was positively correlated with the magnitude of IOP reduction (regression coefficient: 0.251, P=0.02), and negatively correlated with age (regression coefficient: - 0.224, P= 0.04) as well as baseline cup-disk ratio (Regression coefficient: -0.212,P= 0.05) Eyes with a larger negative LC displacement were more likely to experience an HVF improvement of more than 3 dB gain in mean deviation (P= 0.002). Conclusion: A lower SDOCT cup-disc ratio, younger age, and a larger IOP reduction were correlated with a larger negative LC displacement and improving HVF. Corneal biomechanics did not predict LC displacement.

Background: To evaluate the effect of systemic erythropoietin, as well as oral steroids, in the management of recent onset non-arteritic anterior ischemic optic neuropathy (NAION). Method: Ninety-nine eyes of 99 patients diagnosed with NAION within 5 days of onset were included in this single masked randomized clinical trial. Thirty-four patients were randomized into group 1 (systemic erythropoietin), group 2 (oral steroids), and group 3 (control). Group A received 10,000 units of erythropoietin twice a day for three days. Group B received oral prednisone 75 mg daily for two weeks followed by a tapering dose (70 mg for 5 days, 60 mg for 5 days, and 5 mg reductions thereafter every 5 days). Functional and structural outcomes were analyzed at 3 and 6 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measure, and mean deviation (MD) of visual field (VF) test and peripapillary retinal nerve fiber layer thickness (PRNFLT) were secondary outcome measures. Results:The mean BCVA (±SD) at the time of presentation was 1 ± 0.56, 1.01 ± 0.6, and 0.94 ± 0.47 logMAR in groups A, B, and C, respectively (P = 0.140); corresponding values were 0.72 ± 0.45, 0.83 ± 0.46, and 0.78 ± 0.4 logMAR (P = 0.417), and at 6-month follow-up, they were 0.70 ± 0.44, 0.73 ± 0.35, and 0.75 ± 0.39 logMAR, respectively (P = 0.597). Fifty-five percent of patients in group A vesus 34.3% in group B, and 31.2% in group C had an improvement of at least 3 lines in the BCVA values at the 6th-month follow-up visit. (P= 0.04) The mean deviation (MD) at the time of presentation was 19.67 ± 6.2, 20.83 ± 4.83, and 18.94 ± 6.92 decibels (db), respectively (P= 0.483).The corresponding values at month 3 were 18.22 ± 7.5, 19.82 ± 7.15, and 17.65 ± 7.22 db, (P = 0.848); and at month 6 they were 16.56 ± 7.08, 18.15 ± 6.57, and 15.9 ± 5.97 db, respectively. (P = 0.699) PRNFLT at presentation was 189 ± 58, 193 ± 64, and 199 ± 62 micrometers, respectively (P = 0.779), which decreased to 110 ± 45, 127 ± 37, and 119 ± 37 at month 3 (P = 0.423). The corresponding values for month 6 were 88 ± 12, 74 ± 25, and 71 ± 18, respectively (P = 0.041). Conclusion: The findings of our study indicate the beneficial effects of systemic erythropoietin in preserving the function and structure of the optic nerve in recent onset NAION.

Purpose: To evaluate the efficacy and survival rates of trabectome-mediated ab interno trabeculectomy combined with non-fenestrated Baerveldt glaucoma implants (BT) in comparison to Baerveldt glaucoma implant alone (B).Method: A total of 175 eyes undergoing primary glaucoma surgery (60 eyes BT and 115 B) were enrolled in this retrospective comparative case series. Participants were identified using the procedural terminology codes. Groups were then matched using Coarsened Exact Matching (51 eyes in each group). The primary outcome measure was surgical success, defined as 5 mmHg < IOP ≤ 21 mmHg, and IOP reduction ≥ 20% from baseline, and no reoperation for glaucoma. Secondary outcome measures were intraocular pressure, the number of glaucoma medications, and best corrected visual acuity (BCVA).Results: The cumulative probability of success at one year was 61% in BT, and 50% in B. IOP decreased significantly from 23.5±2.4 mmHg at baseline to 14.1±2.7 mmHg at the final follow up in BT (P= 0.001). The corresponding numbers for B were 23.2± 2.0 and 13.9± 1.6, respectively (P= 0.001). There was no significant difference in IOP at the final follow-up (P=0.56). The number of medications at baseline was 2.3±0.3 in both groups. However, BT needed significantly fewer drops at all postoperative time intervals and used 1.1±0.3 (BT) and 2.0±0.4 eye drops (B) at the final follow-up visit (P= 0.004). No dangerous hypotony or hypertension occurred in BT.Conclusion: Similar rates of success and IOP reduction were observed in BT and B. BT needed significantly fewer glaucoma medications. Tube fenestration was not necessary in BT resulting in less postoperative hypotony and hypertension.

Purpose: To compare the efficacy and safety of graft-free short tunnel small flap (STSF) technique with that of scleral patch graft (SPG) in Ahmed glaucoma valve (AGV) implantation. Design: Randomized clinical trial. Participants: Eighty-eyes of eighty patients with medically uncontrolled glaucoma including 41 in STSF and 39 eyes in SPG. Methods: Patients were enrolled and assigned randomly to STSF or SPG. Main Outcome Measures: tube exposure, Intraocular pressure (IOP), number of glaucoma medications, best corrected visual acuity (BCVA), surgical complications, and success rate ( defined as intraocular pressure (IOP) >5 mmHg, ≤21 mmHg, and IOP reduction ≥20% from baseline at two consecutive visits after three months, no reoperation for glaucoma). Results: only one case in SPG developed tube exposure at 1-year follow-up. The cumulative probability of success during the first year of follow-up was 70% in the STSF and 65% in SPG (P = 0.36). IOP decreased significantly from 29.6 ± 8.6 mmHg at baseline to 16.4 ± 3.6 mmHg at the final follow-up in STSF (p = 0.001). The corresponding numbers for SPG were 30.9 ± 11.2 and 15.8 ± 4.7, respectively (p = 0.001). The final IOP was comparable between both groups (p = 0.65). Mean ± standard deviation of the number of glaucoma medications was 1.8 ± 0.9 in STSF and 1.6 ± 0.9 in SPG at final follow-up (P = 0.32). Postoperative complications developed in 8 patients (19%) in STSF and 9 patients (23%) in SPG (P = 0.81). Conclusions: STSF and SPG techniques had comparable complication rate at one-year follow-up. Both techniques were comparable in terms of success rate, postoperative IOP, and glaucoma medications.

Purpose: To evaluate the efficacy and survival rates of same session ab interno trabeculectomy with the trabectome and Ahmed glaucoma valve implant (AT) in comparison to the Ahmed glaucoma valve alone (A). Method: A total of 107 eyes undergoing primary glaucoma surgery were enrolled in this retrospective comparative case series, including 48 eyes which underwent AT and 59 eyes which received A alone. Participants were identified using the procedural terminology codes, and their medical records were reviewed. The primary outcome measure was surgical success, defined as intraocular pressure (IOP) > 5 mmHg, ≤ 21 mmHg, and IOP reduction ≥ 20% from baseline at two consecutive visits after three months, no reoperation for glaucoma. Secondary outcome measures were IOP, the number of glaucoma medications, incidence of a hypertensive phase, and best corrected visual acuity (BCVA). Results: The cumulative probability of success at one year was 70% in AT, and 65% in A (p=0.85). IOP decreased significantly from 26.6 ± 10.1 mmHg at baseline to 14.7 ± 3.3 mmHg at the final follow-up in AT (p= 0.001). The corresponding numbers for A were 28.8 ± 10.2 and 16.7 ± 4.9, respectively (p= 0.001). The final IOP was significantly lower in AT (p= 0.022). The number of medications at baseline was comparable in both groups (2.6 ± 1.2 in AT and 2.5 ± 1.3 in A, p=0.851). Corresponding number at 1 year visit was 1.2±2 in AT and 2.8±1.8 in A (p=0.001). The incidence of a hypertensive phase was 18.7% in AT and 35.5% in A (p=0.05). HP resolved in only 30% of eyes. The criteria for HP resolution were fulfilled in 9 eyes (30%). There was no difference in the rate of resolution of the hypertensive phase between AT and A (33.3% and 28.5%, respectively, p=0.67). Conclusion: Ahmed glaucoma valve implant with same session trabectome surgery significantly decreased the rate of the hypertensive phase and postoperative IOP as well as the number of glaucoma medications.

Purpose: To investigate the extent of anterior chamber angle circumference needed to maintain a physiological outflow facility (C). Methods: Twenty anterior segments of porcine eyes were assigned to 5 groups, each with a different degree of cyanoacrylate-mediated angle closure: 90° (n = 4), 180° (n = 4), 270° (n = 4), 360° (n = 4) and four unoccluded control eyes. The outflow facility was measured at baseline, 3, 12, 24, and 36 hours after angle closure. Outflow patterns were evaluated with canalograms and the histomorphology was compared. Results: Baseline outflow facilities of the five groups were similar (F = 0.922, P = 0.477). Complete, circumferential occlusion over 360° induced a significant decrease in facility from baseline at all time-points (P ≤ 0.023 at 3, 12, 24 and 36 hours). However, no difference from baseline was found in any of the partially-occluded (0–270°) groups (F ≥ 0.067, P ≥ 0.296 at 3, 12, 24 and 36 hours). The canalograms confirmed the extent of occlusion with flow through the unblocked regions. Histology revealed no adverse effects of blockage on the TM or aqueous plexus in the unoccluded angle portions. The unoccluded TM appeared normal. Conclusion: Cyanoacrylate-mediated angle occlusion created a reproducible angle closure model. 90° of unoccluded anterior chamber angle circumference was sufficient to maintain physiological outflow. This model may help understand how outflow can be regulated in healthy, nonglaucomatous TM.

Purpose: To analyze the five-year results of Trabectome ab interno trabeculectomy of a single glaucoma center. Method: In this retrospective interventional single-center case series, data of 93 patients undergoing ab interno trabeculotomy between September 2010, and December 2012 were included. Kaplan-Meier analysis was performed using success criteria defined as postoperative intraocular pressure (IOP) ≤21 mm Hg, or >20% reduction from preoperative IOP, and no need for further glaucoma surgery. Risk factors for failure were identified using Cox proportional hazards ratio (HR). Results: The retention rate for five years follow-up was 66%. The cumulative probability of success at 1, 2, 3, 4 and 5 years was 82.6%, 76.7%, 73.9%, 72.3%, and 67.5%. Risk factors for failure were lower baseline IOP (HR=0.27, P=0.001), younger age (HR=0.25, P=0.02), and higher central corneal thickness (HR=0.18, P= 0.01). Pseudoexfoliation was associated with a higher success rate (HR= 0.39, P=0.02). IOP was decreased significantly from 20.0±5.6 mmHg at baseline to 15.6±4.6 mmHg at 5-year follow-up (P=0.001). The baseline number of glaucoma medications was 1.8±1.2, which decreased to 1.0±1.2 medications at 5 years. Conclusion: Trabectome surgery was associated with a good long-term efficacy and safety profile in this single-center case series with a high retention rate. A higher baseline IOP, older age, thinner cornea, and pseudoexfoliation glaucoma were associated with a higher success rate.

Purpose: To evaluate three different microincisional ab interno trabeculectomy procedures in a porcine eye perfusion model. Methods: In perfused porcine anterior segments, 90 degrees of trabecular meshwork (TM) were ablated using the Trabectome (T; n = 8), Goniotome (G; n = 8), or Kahook device (K; n = 8). After 24 hours, additional 90 degrees of TM were removed. Intraocular pressure (IOP) and outflow facility were measured at 5 µL/min and 10 µL/min perfusion to simulate an elevated IOP. Structure and function were assessed with canalograms and histology. Results: At 5 µL/min infusion rate, T resulted in a greater IOP reduction than G or K from baseline (76.12% decrease versus 48.19% and 47.96%, P = 0.013). IOP reduction between G and K was similar (P = 0.420). Removing another 90 degrees of TM caused an additional IOP reduction only in T and G but not in K. Similarly, T resulted in the largest increase in outflow facility at 5 µL/min compared with G and K (first ablation: 3.41 times increase versus 1.95 and 1.87; second ablation: 4.60 versus 2.50 and 1.74) with similar results at 10 µL/min (first ablation: 3.28 versus 2.29 and 1.90 (P = 0.001); second ablation: 4.10 versus 3.01 and 2.01 (P = 0.001)). Canalograms indicated circumferential flow beyond the ablation endpoints. Conclusions: T, G and K significantly increased the outflow facility. In this model, T had a larger effect than G and K.

Purpose: To correlate outflow function and outflow tract vessel diameter changes induced by nitric oxide (NO). Methods: In a porcine anterior segment perfusion model, the effects of a nitric oxide donor (100 µM DETA-NO) on outflow facility were compared to controls (n=8 per group) with trabecular meshwork (TM) and after circumferential ab interno trabeculectomy (AIT). Outflow structures were assessed with spectral domain optical coherence tomography (SD-OCT) before and after NO, or an NO synthase inhibitor (100 µM L-NAME) and the vasoconstrictor, endothelin-1 (100 pg/mL ET-1). Scans were processed with a custom macro script and aligned for automated reslicing and quantification of cross-sectional outflow tract areas (CSA). Results: The facility increased after DETA-NO (0.189±0.081 μL/min·mmHg, p=0.034) and AIT (0.251±0.094 μL/min·mmHg, p=0.009), respectively. Even after AIT, DETA-NO increased the facility by 61.5% (0.190±0.074 μL/min·mmHg, p=0.023) and CSA by 13.9% (p<0.001). L-NAME + ET-1 decreased CSA by -8.6% (p<0.001). NO increased the diameter of focal constrictions 5.0±3.8 fold. Conclusions: NO can dilate vessels of the distal outflow tract and increase outflow facility in a TM-independent fashion. There are short, focally constricting vessel sections that display large diameter changes and may have a substantial impact on outflow.

Purpose: To investigate whether microsurgical excision of trabecular meshwork (TM) in an ex vivo pigmentary glaucoma model can normalize the hypertensive phenotype. Methods: Eight eyes of a porcine pigmentary glaucoma model underwent 90° of microsurgical TM excision with an aspirating dual-blade (Goniotome (G)). 24 hours later, an additional 90° of TM were removed. Anterior segments with sham surgeries served as the control (C). Outflow facility and intraocular pressure (IOP) were analyzed. Histology with hematoxylin and eosin (H&E) was obtained. Results: After the first 90° TM excision, IOP was significantly lower in G (10.23±2.39 mmHg, n=7) than C (20.04±1.97mmHg, n=8, P<0.01). Outflow facility in G (0.38±0.07 µl/min/mmHg) was higher than C (0.16±0.02 µl/min/mmHg, P<0.01). After the second 90° TM excision, IOP in G (6.46±0.81 mmHg, n=7) was significantly lower than C (20.25±1.66 mmHg, n=8, P<0.001), while the outflow facility in G (0.50±0.05 µl/min/mmHg, n=7) was higher than C (0.16±0.01 µl/min/mmHg, n=8, P<0.001). Compared to the first excision, excision of an additional 90° did not change of IOP (P=0.20) or outflow facility (P=0.17) further. Conclusion: Excision of 90° of TM in a pigmentary glaucoma model using an aspirating dual-blade decreased IOP and increased outflow facility. Translational Relevance: Microsurgical TM excision over 90° can effectively restore outflow in pigmentary glaucoma.

Purpose: To create a highly balanced comparison of ab interno trabeculectomy (Trabectome, AIT) and trabecular bypass stenting (iStent, TBS).Setting: Eye and Ear Institute, Pittsburgh, Ross Eye Institute, Buffalo, and Glaucoma Associates of Texas, Dallas, USA.Design: Retrospective Exact Matching analysis.Methods: AIT and TBS patients were included from three large glaucoma practices. The primary outcome measure was the unmedicated IOP ≤ 21 mmHg at 2-year follow-up visit. A secondary measure was unmedicated IOP reduction ≥ 20% at 2 years. Patients were matched by baseline IOP, the number of glaucoma medications and glaucoma type using Exact Matching and by age using Nearest Neighbor matching. Patients without a close match were excluded. All surgeries were combined with phacoemulsification. Results: 154 AIT and 110 TBS eyes were analyzed. 48 AIT patients were exactly matched to 48 TBS patients. Both groups had a baseline IOP of 15.3±3.1 mmHg. At 24 months, the mean IOP was 13.9±3.3 for AIT versus 16.8±2.8 mmHg for TBS (p=0.04), while the number of medications was 0.7±1.0 for AIT versus 1.7±1.2 for TBS (p=0.04). The proportion of subjects achieving IOP ≤ 21 mmHg without medications at 24 months was 53% in AIT versus 16.6% in TBS (P < 0.05). At 24-month follow up 17.6% of patients in AIT had ≥ 20% IOP reduction without medication versus no patient in TBS. Conclusions: An Exact Matching comparison of AIT and TBS demonstrated greater IOP reduction with fewer medications in AIT.