A new, minimally invasive procedure for dogs with encapsulated Ahmed drainage implants and elevated intraocular pressures: A case series.

OBJECTIVE: To describe a novel, minimally invasive method for re-establishing aqueous humor outflow in dogs with refractory glaucoma after fibrous encapsulation of their Ahmed drainage implants. PROCEDURE: Three dogs (4 eyes) underwent trans-capsular implantation of an Alcon EX-PRESS® glaucoma filtration device under sedation (2 dogs) or general anesthesia (1 dog). After rotating the eye downwards, a 2 mm incision was made in the conjunctiva/Tenon's capsule overlying the encapsulated Ahmed plate, and later closed with absorbable suture. All eyes received subconjunctival mitomycin-C 0.02 mg. RESULTS: Mean post-operative follow-up was 341 days (range: 77-530). All eyes were hypertensive pre-operatively (mean IOP: 31.25 ± 7.14 mmHg) despite receiving topical latanoprost (4/4), timolol (4/4), carbonic anhydrase inhibitors (4/4), and demecarium bromide (2/4). Two eyes (dogs 1 and 2) were visual pre-operatively, while 2 eyes (dog 3) displayed equivocal or no vision. Post-operatively, all eyes received timolol and a carbonic anhydrase inhibitor. Other anti-hypertensive medications were discontinued. Immediately following surgery, all eyes were mildly hypotensive (mean IOP: 5.75 ± 1.71 mm Hg). Two of 4 eyes were normotensive and visual until days 90 (dog 2) and 530 (dog 1) (IOP range: 10-16 mm Hg). One eye (dog 3) was normotensive for approximately 150 days, and then hypertension returned. One eye (dog 3) from the start displayed severe uveitis, hypertensive episodes, and was phthisical by the end of follow-up. CONCLUSIONS: Trans-capsular EX-PRESS® implantation is a minimally invasive procedure for treatment of refractory glaucoma in dogs with encapsulated Ahmed drainage implants, and further investigation is warranted.

Bilateral anterior segment dysgenesis and persistent fetal vasculature associated with terminal 10q26 deletion.

Deletion of the 26q position on chromosome 10 results in a syndrome with well-documented systemic phenotypes. There are few reports of ophthalmic manifestations in terminal 10q26 deletion. We report a 4-week-old boy with terminal 10q26 deletion who had extensive ophthalmic abnormalities, including bilateral anterior segment dysgenesis and bilateral persistent fetal vasculature, with microphthalmia, microcornea, iris corectopia, congenital cataracts, and posterior embryotoxon.

Comparison of Outcomes Following Glaucoma Drainage Tube Surgery Between Primary and Secondary Glaucomas, and Between Phakic and Pseudophakic eyes.

PURPOSE: To report outcomes of glaucoma drainage device (GDD) surgery based on primary or secondary glaucoma diagnosis and lens status. DESIGN: Single-center, retrospective, consecutive cohort study. METHODS: University of Florida patients aged 18 to 93 years who underwent nonvalved GDD surgery between 1996 and 2015 with a minimum of 1-year follow-up were examined. Of the 186 eyes of 186 patients enrolled, 108 had a primary glaucoma and 78 a secondary glaucoma diagnosis. Excluding 13 aphakic patients, 57 eyes were phakic and 116 pseudophakic. Mean intraocular pressure (IOP), mean number of medications, visual acuity (VA), surgical complications, and failure (IOP ≥18 mm Hg, IOP <6 mm Hg, reoperation for glaucoma, or loss of light perception) were the main outcome measures. RESULTS: No significant difference was noted in mean IOP and mean medication use (12.8 ±â€Š4.5 and 13.0 ±â€Š6.6 mm Hg on 2.0 ±â€Š1.2 and 1.5 ±â€Š1.1 medication classes, respectively), mean VA (1.08 ±â€Š0.98 and 0.94 ±â€Š0.89, respectively), failure, or numbers of complications and reoperations (P > 0.05) between eyes with primary and secondary glaucomas at up to 5 years postoperatively. Comparison of phakic and pseudophakic eyes showed a statistically significant higher success rate for the pseudophakic patient group at the ≥18 mm Hg upper limit and <6 mm Hg lower limit (P = 0.01), and significantly fewer eyes required reoperation to lower IOP (6.9% vs 23%). CONCLUSIONS: GDD surgery appears equally effective for secondary glaucomas as for primary glaucomas, and has a better outcome for pseudophakic eyes than phakic eyes.

Comparison of Outcomes of Glaucoma Drainage Implant Surgery With or Without Prior Failed Trabeculectomy.

PRECIS: A comparison of 186 glaucoma patients with mixed diagnoses who underwent nonvalved glaucoma drainage device (GDD) implant surgery showed similar long-term intraocular pressure (IOP), medication, and visual acuity (VA) outcomes between those with prior failed trabeculectomy surgery versus those without. PURPOSE: The purpose of this study was to evaluate whether prior failed trabeculectomy adversely affects the outcome of glaucoma tube surgery. PATIENTS AND METHODS: A total of 186 eyes of 186 patients who underwent a nonvalved GDD implant surgery by a single surgeon between 1996 and 2015 at a University practice were included. Patients were of mixed diagnoses and over 18 years old. Before the GDD surgery, 65 had a previous failed glaucoma filtering surgery and 121 had no prior glaucoma surgery. Demographic information, preoperative and postoperative IOP, medication, VA, and complications were collected from chart review. RESULTS: No significant difference was noted in mean IOP and mean medication use (13.0 and 12.6 mm Hg on 2.0 and 1.7 medication classes at 5 y postoperatively, respectively), mean VA and change in VA from baseline, or numbers of complications (P>0.05), between eyes that had a prior failed filtration surgery and those that had not. Kaplan-Meier plots for failure over 5 years using a lower limit of <5 mm Hg and an upper limit of ≥18, ≥15, or ≥12 mm Hg did not show a significant difference between groups. Subanalyses were performed to examine only primary glaucoma eyes and results were similar. Further group subanalyses comparing those with baseline IOP ≥25 or <25 mm Hg, age 65 and above or below 65 years and those specifically with Baerveldt 350 mm2 implants also did not show significant differences. CONCLUSION: Prior failed filtration surgery does not appear to affect the outcome of future GDD surgery.

Attaining Intraocular Pressure of ≤10 mm Hg: Comparison of Tube and Trabeculectomy Surgery in Pseudophakic Primary Glaucoma Eyes.

PURPOSE: The aim of this study is to evaluate whether trabeculectomy with antimetabolites or glaucoma drainage device (GDD) surgery is more likely to achieve an intraocular pressure (IOP) ≤10 mm Hg. DESIGN: Retrospective, nonrandomized, cohort study of pseudophakic, primary glaucoma patients. METHODS: 53 pseudophakic patients underwent trabeculectomy and 65 received GDD at the University of Florida by one surgeon between 1993 and 2015. The main outcome measures were mean IOP and percentage of patients obtaining an IOP ≤10 mm Hg for up to 5 years postoperatively. A subgroup undergoing a first time glaucoma surgery was also analyzed because there were more redo glaucoma procedures in the GDD group. RESULTS: Over 5 years, the mean annual IOP for the trabeculectomy eyes was between 6.9 and 7.8 mm Hg on an average of 0.2 medications, and that for GDD eyes was between 11.4 and 12.1 mm Hg on a mean of 1.6 to 1.9 medications (P < 0.002). A significantly higher percentage of trabeculectomy eyes than GDD eyes achieved a pressure of ≤10 mm Hg, for years 1 to 4 (P < 0.05). Visual acuity (VA) change was not statistically different between the groups, both for mean logMAR acuity and percentage of patients that lost ≥2 Snellen lines. Complication rates were similar between the groups. Postoperative VA change was similar for eyes achieving low IOP ≤5 mm Hg and those eyes with an IOP ≥10 mm Hg. CONCLUSIONS: Trabeculectomy provided significantly lower IOP for 5 years postoperatively in pseudophakic primary glaucoma patients, and was more likely to achieve an IOP ≤10 mm Hg.

Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid.

AIM: The aim of this study is to assess the effectiveness of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDI) with a broad spectrum epigenetic activity, in improving filtration bleb survival as an adjunct therapy to glaucoma filtration surgery (GFS) in the rabbit model. MATERIALS AND METHODS: Eighteen New Zealand White rabbits underwent GFS in the left eye and were randomized to receive either a subconjunctival (SC) injection of 0.1 mL SAHA (9.25 µg/mL) or balanced saline solution (BSS) at the end of surgery, or a 3-minute intraoperative topical application of 0.4 mg/mL mitomycin-C (MMC). Bleb survival and histology were compared. RESULTS: Blebs of rabbits receiving injections of SAHA survived an average (mean ± SD) of 23.2 ± 2.7 days. SAHA rabbits showed a nonsignificant improvement over rabbits that received an injection of BSS, which had a mean survival time of 19.7 ± 2.7 days (p = 0.38) according to a one-way analysis of variance (ANOVA). Eyes receiving intraoperative topical MMC survived an average of 32.5 ± 3.3 days, which is significantly longer than both the control group treated with BSS (p = 0.01) and the experimental group treated with the SAHA (p = 0.0495). SAHA was well tolerated and showed no significant avascularity, necrosis, or conjunctival thinning. CONCLUSION: Although it was well tolerated, a single intraoperative injection of SAHA did not significantly prolong bleb survival in the rabbit model. CLINICAL SIGNIFICANCE: Epigenetic adjuncts hold promise for improving GFS outcome; however, future studies must continue to examine different administration protocols and dosages to substantiate their efficacy. HOW TO CITE THIS ARTICLE: Rodgers CD, Lukowski ZL, et al. Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid. J Curr Glaucoma Pract 2019;13(1):37-41.

The impact of conjunctival flap method and drainage cannula diameter on bleb survival in the rabbit model.

PURPOSE: To examine the effect of cannula diameter and conjunctival flap method on bleb survival in rabbits undergoing cannula-based glaucoma filtration surgery (GFS). METHODS: Twelve New Zealand White rabbits underwent GFS in both eyes. The twenty-four eyes were divided into four groups. Two of the four groups (N = 12) received limbus-based conjunctival flaps (LBCF), and the other two (N = 12) received fornix-based conjunctival flaps (FBCF). Six FBCF rabbit eyes were implanted with 22-gauge drainage tubes, and the other six were implanted with 26-gauge tubes. Likewise, six LBCF rabbits received 22-gauge drainage tubes and six received 26-gauge tubes. Filtration blebs were evaluated every three days by a masked observer. Bleb failure was defined as the primary endpoint in this study and was recorded after two consecutive flat bleb evaluations. RESULTS: Group 1 (LBCF, 22- gauge cannula) had a mean bleb survival time (Mean ± SD) of 18.7 ± 2.9 days. Group 2 (LBCF, 26-gauge cannula) also had a mean bleb survival time of 18.7 ± 2.9 days. Group 3 (FBCF, 22-gauge cannula) had a mean bleb survival time of 19.2 ± 3.8 days. Group 4 (FBCF, 26-gauge cannula) had a mean bleb survival time of 19.7 ± 4.1 days. A 2-way analysis of variance showed that neither surgical approach nor cannula gauge made a statistically significant difference in bleb survival time (P = 0.634 and P = 0.874). Additionally, there was no significant interaction between cannula gauge and conjunctival flap approach (P = 0.874), suggesting that there was not a combination of drainage gauge and conjunctival flap method that produced superior bleb survival. CONCLUSION: Limbus and fornix-based conjunctival flaps are equally effective in promoting bleb survival using both 22 and 26-gauge cannulas in the rabbit model. The 26-gauge drainage tube may be preferred because its smaller size facilitates the implantation process, reducing the risk of corneal contact.

Comparing glaucomatous disc change using stereo disc viewing and the MatchedFlicker programme in glaucoma experts and trainees.

BACKGROUND/AIMS: The objective of this study is to evaluate the accuracy and speed of trainees and experienced glaucoma specialists using the MatchedFlicker software against the manual examination of stereoscopic disc photographs for detecting glaucomatous optic disc change. METHODS: Three experienced glaucoma specialists, two resident ophthalmologists and one glaucoma fellow from multiple institutions independently evaluated the same 140 image pairs from 100 glaucomatous/ocular hypertensive eyes using a handheld stereo viewer and the MatchedFlicker programme. Fifty had progression to glaucoma as determined by the Ocular Hypertension Treatment Study (OHTS) Optic Disc Reading Group and endpoint committee, and 50 more were negative controls for progression with photos taken a few minutes apart. Twenty photo pairs from each of the two groups were duplicated for reviewer variability analysis. The initial viewing method was randomised and then alternated for each group of 70 image pairs. Reviewer accuracy and evaluation time for each method were measured. RESULTS: Evaluators averaged 8.6 s faster per image pair (26%) with the MatchedFlicker programme than with the stereo viewer (p=0.0007). Evaluators correctly identified more image pairs when using the MatchedFlicker software over the stereo viewer (p=0.0003). There was no significant difference between the expert and trainee group in speed or overall accuracy for either method. Experts were significantly more consistent than trainees with the duplicate image pairs (p=0.029). Trainees appeared more reluctant to designate eyes as showing glaucoma progression than experts. CONCLUSIONS: Both expert glaucoma specialists and ophthalmologists in various stages of training had greater accuracy and speed with the MatchedFlicker programme than with a handheld stereoscopic viewer.

Development of a microarray chip for gene expression in rabbit ocular research.

PURPOSE: To develop a microarray for the rabbit that can be used for ocular gene expression research. METHODS: Messenger RNA was isolated from anterior segment tissues (cornea, conjunctiva, and iris) and posterior segment tissues (lens, retina, and sclera) of rabbit eyes and used to create two independent cDNA libraries through the NEIBank project. Clones from each of these libraries were sequenced from both the 5' and 3' ends. These sequences and those from the National Center for Biotechnology Information (NCBI) taxonomy database for rabbit were combined and electronically assembled into a set of unique nonoverlapping continuous sequences (contigs). For each contig, a homology search was performed using BLASTX and BLASTN against both the NCBI NR and NT databases to provide gene annotation. Unique contigs were sent to Agilent Technologies, where 60 base oligonucleotide probes were designed and synthesized, in situ, on two different arrays in an 8 array x 1900 element format. Glaucoma filtration surgery was performed on one eye of six rabbits. After 14 days, tissue was harvested from the conjunctiva and Tenon's capsule of both the surgically treated and untreated control eyes. Total RNA from each sample was labeled with cyanine dyes and hybridized to our custom microarrays. RESULTS: Of the 3,154 total probes present on the two arrays, 2,522 had a signal value above the background. The expression of 315 genes was significantly altered by glaucoma filtration surgery. Genes whose expression was altered included proteins associated with inflammatory response, defense response, and proteins involved in synthesis of the extracellular matrix. CONCLUSIONS: The results of this rabbit microarray study are consistent with those from other wound healing studies, indicating that this array can provide valid information on broad patterns of gene expression. This is the first microarray available for rabbit studies and is a valuable tool that can be used to study molecular events in the eye.

Relationship between Glaucoma Drainage Device Size and Intraocular Pressure Control: Does Size Matter?

There is ambiguity in the literature regarding whether a larger glaucoma drainage device (GDD) achieves a lower long-term intraocular pressure (IOP). There is some evidence on both sides, but overall there seems to be an optimal surface area of approximately 200-250 mm2 beyond which there may be little advantage to increasing the plate size for most patients. HOW TO CITE THIS ARTICLE: Rodgers CD, Meyer AM, Sherwood MB. Relationship between Glaucoma Drainage Device Size and Intraocular Pressure Control: Does Size Matter? J Curr Glaucoma Pract 2017;11(1):1-2.

Retrospective Comparison of Intermediate-term Efficacy of 350 mm2 Glaucoma Drainage Implants and Medium-sized 230-250 mm2 Implants.

AIM: To compare the intermediate-term efficacy of a large surface area Baerveldt 350 mm2 glaucoma drainage device (GDD) with medium surface area implants (Baerveldt 250 mm2 and Molteno 3, 230, or 245 mm2). DESIGN: This is a retrospective, nonrandomized comparative trial. MATERIALS AND METHODS: A total of 94 eyes of 94 patients of mixed glaucoma diagnoses without any prior glaucoma surgical procedures and who had undergone a glaucoma drainage implant surgery with either a large Baerveldt 350 mm2 GDD or a medium-sized GDD (Baerveldt 250 mm2 or Molteno 230 or 245 mm2) were reviewed for intraocular pressure (IOP), number of glaucoma medications, and visual acuity (VA) preoperatively, and at 1, 2, and 3 years postprocedure. RESULTS: No significant differences were found in mean IOP, number of glaucoma medications used, and VA at 1, 2, and 3 years postoperatively. The rate of additional glaucoma procedures was similar between the two groups. CONCLUSION: There is no clear evidence that a larger implant surface area beyond 230 to 250 mm2 is advantageous in providing intermediate-term IOP control. CLINICAL SIGNIFICANCE: It may be technically easier to surgically place a GDD that does not need to have its wings placed underneath the recti muscles, and the IOP results are similar. HOW TO CITE THIS ARTICLE: Meyer AM, Rodgers CD, Zou B, Rosenberg NC, Webel AD, Sherwood MB. Retrospective Comparison of Intermediate-term Efficacy of 350 mm2 Glaucoma Drainage Implants and Medium-sized 230-250 mm2 Implants. J Curr Glaucoma Pract 2017;11(1):8-15.

Twice-daily 0.2% brimonidine-0.5% timolol fixed-combination therapy vs monotherapy with timolol or brimonidine in patients with glaucoma or ocular hypertension: a 12-month randomized trial.

OBJECTIVE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a fixed combination of 0.2% brimonidine tartrate and 0.5% timolol maleate (fixed brimonidine-timolol) compared with the component medications. METHODS: In 2 identical, 12-month, randomized, double-masked multicenter trials, patients with ocular hypertension or glaucoma were treated with fixed brimonidine-timolol twice daily (n = 385), 0.2% brimonidine tartrate 3 times daily (n = 382), or 0.5% timolol maleate twice daily (n = 392). MAIN OUTCOMES MEASURES: Mean change from baseline IOP and incidence of adverse events. RESULTS: The mean decrease from baseline IOP during 12-month follow-up was 4.4 to 7.6 mm Hg with fixed brimonidine-timolol, 2.7 to 5.5 mm Hg with brimonidine, and 3.9 to 6.2 mm Hg with timolol. Mean IOP reductions were significantly greater with fixed brimonidine-timolol compared with timolol at all measurements (P< or =.002) and brimonidine at 8 am, 10 am, and 3 pm (P<.001) but not at 5 pm. The incidence of treatment-related adverse events in the fixed-combination group was lower than that in the brimonidine group (P = .006) but higher than that in the timolol group (P<.001). The rate of discontinuation for adverse events was 14.3% with the fixed combination, 30.6% with brimonidine, and 5.1% with timolol. CONCLUSIONS: Twice-daily fixed brimonidine-timolol therapy provides sustained IOP lowering superior to monotherapy with either thrice-daily brimonidine or twice-daily timolol and is better tolerated than brimonidine but less well tolerated than timolol. APPLICATION TO CLINICAL PRACTICE: Fixed brimonidine-timolol is an effective and convenient IOP-lowering therapy.

Comparing Glaucomatous Disc Change Using Stereo Disc Viewing and the MatchedFlicker Software Program in Ophthalmologists-in-Training.

PURPOSE: To compare the accuracy and speed of using the computerized MatchedFlicker software program (EyeIC Inc, Narberth, Pennsylvania, USA) to evaluate glaucomatous optic disc change against the traditional gold standard of manually examining stereoscopic disc photographs. DESIGN: A prospective evaluation of diagnostic technology. METHODS: Two resident ophthalmologists and 1 glaucoma fellow at the University of Florida independently evaluated 140 image pairs from 100 glaucomatous/ocular hypertensive patient eyes using a handheld stereo viewer and the MatchedFlicker program. Fifty had progression to glaucoma as determined by the Ocular Hypertension Treatment Study (OHTS) Optic Disc Reading Group and the OHTS Endpoint Committee in the OHTS, and 50 more had photographs taken a few minutes apart, which were negative controls with no progression. Twenty photograph pairs from each group were duplicated to determine reviewer variability. Photographs were examined in alternating blocks of 70 photograph pairs for each method, with the starting viewing method randomized. Reviewer accuracy and time to review for each method were measured. RESULTS: Using the handheld stereo viewer, the reviewers correctly identified progression or nonprogression in 76.0% of the slide pairs. Using the MatchedFlicker software, 87.6% were correctly identified (P = .011). Evaluator speed averaged 34.1 seconds per image pair with the stereo viewer vs 24.9 seconds with the MatchedFlicker program (P = .044). Overall, Flicker was significantly more specific but less sensitive than stereo slides. Trainees appeared more reluctant to identify glaucoma progression from slides than from Flicker. For the 2 less experienced trainees Flicker was significantly more accurate. CONCLUSION: The MatchedFlicker software had a greater accuracy and was quicker to perform than using a handheld stereoscopic viewer.

Porosity of Bleb Capsule declines rapidly with Fluid Challenge.

INTRODUCTION: The porosity of the fibrous capsule around a glaucoma drainage device (GDD) may be the most important functional attribute. The factors that determine capsular porosity are not well understood. Failed GDD surgeries are usually associated with thick impervious capsules and components of aqueous have been implicated in this process. PURPOSE: In this study, we interrogated the effect of passage of nonaqueous fluid on capsular porosity in mature (but aqueous naïve) blebs in a previously reported GDD model (the "Center for Eye Research Australia Implant"). MATERIALS AND METHODS: The study was performed at two centers using 17 New Zealand White (NZW) rabbits. An experimental GDD was implanted into the subconjunctival space but without connection to the anterior chamber. After 28 days, balanced salt solution (BSS) was passed through the implant for 30 to 40 minutes at 12 mm Hg. Capsular porosity was measured as flow (µL/min) at a constant pressure. Porosity of the capsule was retested at 3 and 6 days. RESULTS: There was a marked reduction in capsular porosity within 3 days of exposure to BSS (fluid challenge). Even though the baseline porosity was significantly different in the two groups (3.00 ± 0.5 µL/min and 29.67 ± 12.12 µL/min, p < 0.001), the effect of passage of BSS was similar. Capsular porosity fell by approximately 80% in both groups from baseline after single BSS challenge. Capsular thickness was significantly less in Advanced Eye Center (AEC) rabbits at baseline. There was no change in the capsular thickness before and after single fluid challenge. CONCLUSION: Passage of BSS at physiological pressures for under 40 minutes caused marked reduction in the porosity of the fibrous capsule within 3 days. This was not associated with any significant thickening of the fibrous capsule within this time frame. HOW TO CITE THIS ARTICLE: Pandav SS, Ross CM, Thattaruthody F, Nada R, Singh N, Gautam N, Beirne S, Wallace GG, Sherwood MB, Crowston JG, Coote M. Porosity of Bleb Capsule declines rapidly with Fluid Challenge. J Curr Glaucoma Pract 2016;10(3):91-96.

Failed glaucoma drainage implant: long-term outcomes of a second glaucoma drainage device versus cyclophotocoagulation.

BACKGROUND/AIMS: To evaluate long-term efficacy of a second glaucoma drainage device (GDD) versus cyclophotocoagulation (CPC) after failure of primary drainage implant. METHODS: This is a non-randomised, retrospective cohort study. A chart review was conducted of patients who underwent GDD surgery between July 1986 and November 2012 requiring further glaucoma procedures for intraocular pressure (IOP) control. An additional GDD was placed in 15 eyes, while 32 eyes underwent CPC. The main outcome measurement was IOP control and/or time to failure of secondary intervention (IOP >18 mm Hg on two sequential measurements). RESULTS: Mean follow-up after the second procedure was 63±65.8 months (range 6-254 months) in the CPC group and 132±91.8 months (range 12-254 months) in the GDD group. Thirty-four per cent (11/32 eyes) undergoing CPC later required further treatment at a mean of 13.6±10.7 months with 10/11(91%) of additional interventions occurring within 2 years. Despite an initially high success rate for IOP control in the first 5 years, eventually 60% (9/15 eyes) that underwent a second tube required additional treatment at a mean of 73.4 months with only 2/9(22%) requiring this within the first 2 years. The risk of visual acuity worsening by 2 Snellen lines or more at 12 months was 5/14 for the GDD group (36%) and 4/23(17%) for the CPC group. CONCLUSIONS: After failure of an initial drainage implant to control IOP, a sequential tube had a high initial rate of success but a relatively high likelihood of long-term failure, generally after 6 years. Eyes that received CPC tended to fail earlier, often within the first year, but had relatively few late failures.

Sequential Therapy with Saratin, Bevacizumab and Ilomastat to Prolong Bleb Function following Glaucoma Filtration Surgery in a Rabbit Model.

To determine if sequential treatment with Bevacizumab (Avastin), a monoclonal, VEGF antibody that blocks angiogenesis; Saratin, a 12 kD polypeptide with anti-inflammatory and anti-thrombotic properties; and Ilomastat, a matrix metalloproteinase (MMP) inhibitor, prolongs bleb life following glaucoma filtration surgery (GFS) in a rabbit model. Thirty-two New Zealand White rabbits (eight rabbits per group) underwent GFS in the left eye. Group 1 received a perioperative injection of both Saratin and Bevacizumab, and later, subconjuctival injections of Ilomastat on days 8 and 15. Group 2 received only Saratin perioperatively, and also received Ilomastat injections on days 8 and 15. Group 3, the negative control, received a single perioperative injection of Balanced Saline Solution (BSS) along with post-operative BSS injections on days 8 and 15. Group 4, the positive control, received topical treatment with Mitomycin-C (MMC) at the time of surgery with no further treatment. Blebs were evaluated by an observer masked to treatment every third day. Histology was obtained on two eyes in each group on post-op day twelve as well as all eyes following bleb failure. Eyes in group 1 had a mean bleb survival time of 29 ± 2.7 days, whereas those in group 2 that received the experimental treatment without Bevacizumab had a mean survival time of 25.5 ± 2.7 days. An ANOVA test showed that the Saratin/Ilomastat/Bevacizumab group demonstrated a significant prolongation of bleb survival compared to the BSS control-mean survival time of 19.7 ±2.7 days-(p = 0.0252) and was not significantly different from the MMC positive control group (p = 0.4238)-mean survival time of 32.5 ± 3.3. From tissue histology at day 12, the four different groups showed marked differences in the cellularity and capsule fibrosis. The MMC eyes showed minimal cellularity, were avascular and had minimal fibrous tissue. BSS group showed high cellularity, moderate to high fibrosis, and thicker and more defined capsules than either of the treatment groups and the positive control. Both the Saratin/Ilomastat/Bevacizumab and Saratin/Ilomastat only eyes showed moderate cellularity with minimal fibrosis, with less cellularity and fibrosis present in the triple treatment group. Sequential therapy with multiple agents, including Bevacizumab, prolonged bleb function following GFS in the rabbit model and were significantly better than the negative BSS control. The experimental group did not show the same surface tissue histological thinning and side effects associated with MMC treatment.

Microarray analysis of the failure of filtering blebs in a rat model of glaucoma filtering surgery.

PURPOSE: To generate data concerning changes in levels of protein expression associated with wound healing and bleb failure in a rat model of glaucoma filtration surgery (GFS), and to identify factors that may play a role in this process. METHODS: Of 36 Sprague-Dawley rats, GFS was performed on 27 by introducing a silicone cannula through a scleral tunnel under a conjunctival flap, resulting in aqueous-filtering blebs that failed over 8 to 13 days. The additional nine rats were used as the nonsurgical control. Nine blebs were harvested at each of days 0, 2, 5, and 12 and pooled, yielding three replicates of three blebs per time point. RNA was extracted, labeled, and hybridized to 230A rat GeneChip arrays (Affymetrix, Santa Clara, CA). RESULTS: Of the 15,924 probe sets/genes present on the array, 923 genes were indicated to have a significant treatment effect at P < 0.005. Eight gene expression clusters were identified that could be broadly classified into three basic patterns. These were an increase on day 2, a decrease on day 2, or an increase on either day 5 or 12. The greatest change occurred between days 0 and 2. The most heavily populated functional categories included growth factors, structural proteins, and matrix metalloproteinases. CONCLUSIONS: This study represents the first large-scale gene expression analysis after GFS. Expression patterns for known mediators of the bleb scarring process, including transforming growth factor-beta, connective tissue growth factor, and matrix metalloproteinases, were confirmed, and a number of mediators not previously associated with this process were identified.

Expression of connective tissue growth factor after glaucoma filtration surgery in a rabbit model.

PURPOSE: Connective tissue growth factor (CTGF) appears to play a significant role in mediating fibrosis in several tissues. To gain further understanding of the role of CTGF in the scar formation that occurs after glaucoma filtering surgery (GFS), experiments were performed in a rabbit model. METHODS: . Three experiments were performed: (1) CTGF and transforming growth factor (TGF)-beta expression were measured quantitatively after GFS, using ELISA. (2) After GFS conjunctival bleb tissues were immunostained for the presence of CTGF and TGF-beta. (3) Exogenous CTGF was injected into mitomycin-C (MMC)-treated filtering blebs and the scaring response compared to TGF-beta and physiological saline-injected blebs. RESULTS: CTGF and TGF-beta were expressed maximally by day 5 after surgery and were both shown to be present in the bleb tissues after GFS. The addition of exogenous CTGF and TGF-beta increased the rate of failure of GFS blebs. CONCLUSIONS: These data support the hypothesis that CTGF plays an important role in scarring and wound contracture after GFS. Inhibition of CTGF synthesis or its action may help prevent bleb failure and improve long-term GFS outcomes.

Functional and structural analysis of the visual system in the rhesus monkey model of optic nerve head ischemia.

PURPOSE: A redistribution of neurochemicals has been identified in the visual cortex of monkeys with laser-induced glaucoma. Examined were functional, structural, and neurochemical changes to the retina, optic nerve, and central visual system in a nonhuman primate model of optic nerve head (ONH) ischemia caused by sustained unilateral administration of endothelin (ET)-1 to the optic nerve. METHOD: ET-1 or sham control solution was delivered by osmotic minipump to the retrolaminar region of one optic nerve of rhesus monkeys (Macaca mulatta) for 1.5 years. ONH topography and blood flow velocity were serially studied with scanning laser tomography and laser Doppler flowmetry, respectively. Retinal and cortical electrophysiologic measurements from pattern-derived stimuli were obtained quarterly. Immunohistochemistry was used to identify the distribution of calbindin (CB) and c-Fos labeled neurons in the visual cortex areas V1 and V2, and lateral geniculate nucleus (LGN). Retinal ganglion cell counts and optic nerve axon density were determined by light microscopy. RESULTS: No significant changes in retinal and ONH morphology, ONH blood flow velocity, and retinal and cortical pattern-derived functional activity were detected. Measurement of CB-positive cell density in V1 and V2 showed a significant decrease in CB labeling to the contralateral side of the ET-1-treated eye (P < 0.04). CB-positive cells were present in the magnocellular layers of the LGN with no differences noticed between the ET-1- and sham-treated eyes. c-Fos-labeled neurons were found in striate area V1 and extrastriateV2 of both groups. No c-Fos labeling was observed in the LGN. CONCLUSIONS: Administering ET-1 to the orbital optic nerve alters neuronal metabolic activity in the visual cortex in rhesus monkeys. Metabolic activity reductions in the visual cortex precede the ability to detect functional and structural alterations in the retina, ONH, and visual cortex in this animal model.